Publications by authors named "Ludovic Ferrer"

43 Publications

Generation of clinical Lu SPECT/CT images based on Monte Carlo simulation with GATE.

Phys Med 2021 May 3;85:24-31. Epub 2021 May 3.

Département de Médecine Nucléaire, Institut Régional du Cancer de Montpellier (ICM), Montpellier F-34298, France; IRCM, UMR 1194 INSERM, Université de Montpellier and Institut Régional du Cancer de Montpellier (ICM), Montpellier F-34298, France.

Purpose: Patient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.

Methods: This study considers a therapy cycle of 6.85 GBq Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on "Dosimetry in Radiopharmaceutical therapy for personalised patient treatment". Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation.

Results: Gamma index passing rate (2% - 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images.

Conclusions: Realistic Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmp.2021.04.002DOI Listing
May 2021

Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases.

Biomedicines 2020 Nov 28;8(12). Epub 2020 Nov 28.

Department of Radiotherapy and Nuclear Medicine Institut de Cancérologie de l'Ouest (ICO), F-44800 Saint-Herblain, France.

(1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; "iPET") in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using F-deoxyglucose (FDG) for BC or F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines8120548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760481PMC
November 2020

Radiomics for radiation oncologists: are we ready to go?

BJR Open 2020 25;2(1):20190046. Epub 2020 Mar 25.

Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Nantes - Saint Herblain, France.

Radiomics have emerged as an exciting field of research over the past few years, with very wide potential applications in personalised and precision medicine of the future. Radiomics-based approaches are still however limited in daily clinical practice in oncology. This review focus on how radiomics could be incorporated into the radiation therapy pipeline, and globally help the radiation oncologist, from the tumour diagnosis to follow-up after treatment. Radiomics could impact on all steps of the treatment pipeline, once the limitations in terms of robustness and reproducibility are overcome. Major ongoing efforts should be made to collect and share data in the most standardised manner possible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjro.20190046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594896PMC
March 2020

Combining Superpixels and Deep Learning Approaches to Segment Active Organs in Metastatic Breast Cancer PET Images

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1536-1539

Semi-automatic measurements are performed on FDG PET-CT images to monitor the evolution of metastatic sites in the clinical follow-up of metastatic breast cancer patients. Apart from being time-consuming and prone to subjective approximation, semi-automatic tools cannot make the difference between cancerous regions and active organs, presenting a high FDG uptake.In this work, we combine a deep learning-based approach with a superpixel segmentation method to segment the main active organs (brain, heart, bladder) from full-body PET images. In particular, we integrate a superpixel SLIC algorithm at different levels of a convolutional network. Results are compared with a deep learning segmentation network alone. The methods are cross-validated on full-body PET images of 36 patients and tested on the acquisitions of 24 patients from a different study center, in the context of the ongoing EPICUREseinmeta study. The similarity between the manually defined organ masks and the results is evaluated with the Dice score. Moreover, the amount of false positives is evaluated through the positive predictive value (PPV).According to the computed Dice scores, all approaches allow to accurately segment the target organs. However, the networks integrating superpixels are better suited to transfer knowledge across datasets acquired on multiple sites (domain adaptation) and are less likely to segment structures outside of the target organs, according to the PPV.Hence, combining deep learning with superpixels allows to segment organs presenting a high FDG uptake on PET images without selecting cancerous lesion, and thus improves the precision of the semi-automatic tools monitoring the evolution of breast cancer metastasis.Clinical relevance- We demonstrate the utility of combining deep learning and superpixel segmentation methods to accurately find the contours of active organs from metastatic breast cancer images, to different dataset distributions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC44109.2020.9175683DOI Listing
July 2020

Deep learning approaches for bone and bone lesion segmentation on 18FDG PET/CT imaging in the context of metastatic breast cancer

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1532-1535

FDG PET/CT imaging is commonly used in diagnosis and follow-up of metastatic breast cancer, but its quantitative analysis is complicated by the number and location heterogeneity of metastatic lesions. Considering that bones are the most common location among metastatic sites, this work aims to compare different approaches to segment the bones and bone metastatic lesions in breast cancer.Two deep learning methods based on U-Net were developed and trained to segment either both bones and bone lesions or bone lesions alone on PET/CT images. These methods were cross-validated on 24 patients from the prospective EPICURE metastatic breast cancer study and were evaluated using recall and precision to measure lesion detection, as well as the Dice score to assess bones and bone lesions segmentation accuracy.Results show that taking into account bone information in the training process allows to improve the precision of the lesions detection as well as the Dice score of the segmented lesions. Moreover, using the obtained bone and bone lesion masks, we were able to compute a PET bone index (PBI) inspired by the recognized Bone Scan Index (BSI). This automatically computed PBI globally agrees with the one calculated from ground truth delineations.Clinical relevance- We propose a completely automatic deep learning based method to detect and segment bones and bone lesions on FDG PET/CT in the context of metastatic breast cancer. We also introduce an automatic PET bone index which could be incorporated in the monitoring and decision process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC44109.2020.9175904DOI Listing
July 2020

From a PMT-based to a SiPM-based PET system: a study to define matched acquisition/reconstruction parameters and NEMA performance of the Biograph Vision 450.

EJNMMI Phys 2020 Sep 3;7(1):55. Epub 2020 Sep 3.

Nuclear Medicine Department, University Hospital of Nantes, Place Alexis Ricordeau, Nantes, France.

Background: The purpose of this work was to propose an approach based on noise measurement to adapt present clinical acquisition and reconstruction parameters adapted to a PMT-based system (Biograph mCT) to a SiPM-based system (Biograph Vision 450) sharing identical geometrical properties. The NEMA performance (NEMA) of the recently released Biograph Vision 450 PET/CT (Vision) was also derived.

Methods: All measurements were conducted on Vision and Biograph mCT with TrueV (mCT). A full NEMA-based performance was derived for Vision only. The adaptation of acquisition and reconstruction parameters from mCT to Vision was done using the NEMA image quality phantom. The noise level reached using mCT was set as the reference value for six different numbers of net true coincidences. The noise level computed using Vision was matched to the reference noise level (within 0.01%) using a different reconstruction set-up to determine the potential reduction of count numbers for the same noise level.

Results: Vision sensitivity was 9.1 kcps/MBq for a timing resolution of 213 ps at 5.3 kBq/mL. The NEMA-based CR for the 10-mm sphere was better than 75% regardless the reconstruction set-up studied. The mCT reference noise properties could be achieved using Vision with a scan time reduction (STR) of 1.34 with four iterations and a 440 × 440 matrix size (or STR = 1.89 with a 220 × 220 matrix size) together with a 3D CR improvement of 53% for the 10-mm sphere (24% using 220 × 220).

Conclusion: The Vision exhibited improved NEMA performances compared to mCT. Using the proposed approach, the time acquisition could be divided by almost two, while keeping the same noise properties as that of mCT with a marked improvement of contrast recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40658-020-00323-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471223PMC
September 2020

Prognostic Impact of Pretherapeutic FDG-PET in Localized Anal Cancer.

Cancers (Basel) 2020 Jun 9;12(6). Epub 2020 Jun 9.

Nuclear Medicine Unit, ICO Cancer Center, 44805 Saint Herblain, France.

Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient's sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cut-off for discrimination between a low and high risk of event occurrence was 40 cm. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12061512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352672PMC
June 2020

Haute Couture or Ready-to-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection.

Cancers (Basel) 2020 Apr 10;12(4). Epub 2020 Apr 10.

Radiation Oncology Department, Institut de Cancérologie de l'Ouest, 44805 Nantes Saint-Herblain, France.

Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12040944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226011PMC
April 2020

Initial Clinical Results of a Novel Immuno-PET Theranostic Probe in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

J Nucl Med 2020 08 13;61(8):1205-1211. Epub 2020 Mar 13.

Nuclear Medicine, ICO Cancer Center, Nantes, France.

This prospective study evaluated the imaging performance of a novel pretargeting immunologic PET (immuno-PET) method in patients with human epidermal growth factor receptor 2 (HER2)-negative, carcinoembryonic antigen (CEA)-positive metastatic breast cancer, compared with CT, bone MRI, and F-FDG PET. Twenty-three patients underwent whole-body immuno-PET after injection of 150 MBq of Ga-IMP288, a histamine-succinyl-glycine peptide given after initial targeting of a trivalent anti-CEA, bispecific, antipeptide antibody. The gold standards were histology and imaging follow-up. Tumor SUVs (SUV and SUV) were measured, and tumor burden was analyzed using total tumor volume and total lesion activity. The total lesion sensitivity of immuno-PET and F-FDG PET were 94.7% (1,116/1,178) and 89.6% (1,056/1,178), respectively. Immuno-PET had a somewhat higher sensitivity than CT or F-FDG PET in lymph nodes (92.4% vs. 69.7% and 89.4%, respectively) and liver metastases (97.3% vs. 92.1% and 94.8%, respectively), whereas sensitivity was lower for lung metastases (48.3% vs. 100% and 75.9%, respectively). Immuno-PET showed higher sensitivity than MRI or F-FDG PET for bone lesions (95.8% vs. 90.7% and 89.3%, respectively). In contrast to F-FDG PET, immuno-PET disclosed brain metastases. Despite equivalent tumor SUV, SUV and total tumor volume, total lesion activity was significantly higher with immuno-PET than with F-FDG PET ( = 0.009). Immuno-PET using anti-CEA/anti-IMP288 bispecific antibody, followed by Ga-IMP288, is a potentially sensitive theranostic imaging method for HER2-negative, CEA-positive metastatic breast cancer patients and warrants further research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2967/jnumed.119.236000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413237PMC
August 2020

Preliminary results of a Ga-PSMA PET/CT prospective study in prostate cancer patients with occult recurrence: Diagnostic performance and impact on therapeutic decision-making.

Prostate 2019 09 17;79(13):1514-1522. Epub 2019 Aug 17.

Department of Nuclear Medicine, ICO Cancer Center.

Background: In this prospective study (NCT03443609), we investigated the impact of 68Ga-PSMA-11 PET-CT on the treatment plan and therapeutic response obtained for patients with prostate cancer (PCa) presenting a recurrence with a low rising PSA.

Methods: One hundred thirty hormone-naive (PSA < 1.5 ng/mL) patients were enrolled. All patients received radical treatment. PET images were recorded 1 and 2  hours after injection of tracer and interpreted by two independent nuclear physicians. Six months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results.

Results: Data analysis for the first 52 included patients has been completed. 68Ga-PSMA-11-positive lesions were detected in 38/52 (73.1%) patients. Ninety-four lesions were detected as follows, 53/94 in lymph nodes (56.4%), 25/94 in bone (26.6%), and 12/94 into the prostate bed (12.7%). Detection rates were 58%, 81%, and 82% for serum PSA levels lower than 0.25 ng/mL, between 0.25 to ≤ 0.69  ng/mL and 0.70  ng/mL, respectively. As a result of the PSMA PET-CT, therapeutic management changed in 38/52 patients (73.1%). Patients had undetectable serum PSA levels after treatment guided by 68Ga-PSMA-11 PET-CT results in 10/52 (19.2%) cases and with a PSA decrease of over 60% in 18/52 (34.6%) patients.

Conclusion: Whilst our patient population presented a very low PSA level, preliminary results of the 68Ga-PSMA PET-CT study showed recurrence localization in more than half of the patients and this had a major clinical impact, as it resulted in treatment change in more than half of the patients and a significant decrease in PSA levels in a third of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.23869DOI Listing
September 2019

Reoxygenation during radiotherapy in intermediate-risk prostate cancer.

Radiother Oncol 2019 04 12;133:16-19. Epub 2019 Jan 12.

Laboratoire de Traitement de l'Information Médicale (LATIM), INSERM, UMR 1101, Université de Bretagne Occidentale, IBSAM, faculté de médecine, 29238 Brest CEDEX, France.

Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk prostate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiotherapy induces early prostate tumor reoxygenation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2018.12.022DOI Listing
April 2019

68Ga-PSMA-11 PET-CT study in prostate cancer patients with biochemical recurrence and non-contributive 18F-Choline PET-CT: Impact on therapeutic decision-making and biomarker changes.

Prostate 2019 04 14;79(5):454-461. Epub 2018 Dec 14.

Nuclear Medicine Unit, ICO Cancer Center, Saint Herblain, Pays de la Loire, France.

Background: In this retrospective study, we investigated the impact of Ga-PSMA-11 PET-CT (PSMA PET-CT) upon the treatment plan and therapeutic response obtained for Prostate Cancer (PCa) patients presenting an occult biochemical recurrence.

Methods: Forty-two patients with previously negative or doubtful 18F-Choline (FCH) were enrolled. PET images were recorded 1 h after injection of tracer. Only a few months after treatment ended, a PSA assay was requested to evaluate the therapeutic efficacy of the treatment based on PSMA results.

Results: PSMA-positive lesions were detected in 34/42 (80.9%) patients. Detection rates were 85.7% and 89.3% for serum PSA levels lower than 2 ng/mL, and >2 ng/mL, respectively. One hundred seventy-three lesions were detected: 132/173 in lymph nodes (76.3%), 22/173 as metastatic sites (bone or lung) (12.7%), and 19/173 in the prostate bed (10.9%). As a result of the PSMA PET-CT, therapeutic management changed in 31/42 patients (73.8%). With a follow-up of 4.9 ± 2.27 months, 32/42 (76.2%) PSA assays after treatment guided by PSMA PET-CT were collected. For 37.5% (12/32) of patients, the serum PSA level was lower than 0.2 ng/mL and a PSA decrease of over 50% in 8 (25.0%) other patients were obtained.

Conclusion: Performing a PSMA PET-CT when FCH PET-CT was doubtful or negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 70% of patients as well as a significant decrease in PSA levels in more than 60% of them.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pros.23751DOI Listing
April 2019

Advantages of systematic trunk SPECT/CT to planar bone scan (PBS) in more than 300 patients with breast or prostate cancer.

Oncotarget 2018 Aug 3;9(60):31744-31752. Epub 2018 Aug 3.

Nuclear Medicine Unit, ICO Cancer Center, Saint Herblain, France.

Propose: The aim of our study was to evaluate the potential benefit of a systematic trunk SPECT/CT associated with a Planar Bone Scan (PBS) in breast cancer (BC) and prostate cancer (PCa) patients at initial staging or recurrence.

Results: In 328 patients, sensitivities and specificities were between 74.4-93% and 78.8-97.5% for PBS and 97.7-100% and 96.8-98.6% for SPECT/CT respectively. PBS was considered equivocal for 67 compared to only 6 patients for trunk SPECT/CT. Regardless of "optimistic" or "pessimistic" analysis of equivocal trunk SPECT/CT lesions, the trunk SPECT/CT was almost perfect, allowing to rely on this result for excluding metastatic disease which was corroborated by ROC curve analysis. The trunk SPECT/CT allowed downstaging for 62 patients (19%) and upstaging for 11 patients.

Materials And Methods: PBS and a trunk SPECT/CT were systematically performed in all patients. Independent review of PBS and trunk SPECT/CT was performed for each patient and an abnormality interpretative score (Sc) with 3 levels was built: Sc 1: metastatic or probably metastatic pattern, Sc 2: equivocal pattern, Sc 3: benign or probably benign pattern or no abnormality. The bone pattern status was defined by at least 1 year follow-up. The clinical impact was evaluated in terms of down and upstaging in patient analysis.

Conclusions: Trunk SPECT/CT improves the performance of PBS in BC and PCa assessments and results in improvements in both the detection performance of bone metastases as well as a better characterization of equivocal lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.25860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114966PMC
August 2018

Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using F-fluoromisonidazole PET/CT: a pilot study.

Oncotarget 2018 Feb 13;9(11):10005-10015. Epub 2018 Jan 13.

Laboratoire de Traitement de l'Information Médicale (LaTIM), INSERM, UMR 1101, IBSAM, UBO, UBL, IBRBS, Faculté de Médecine, 29238 Brest, France.

Purpose: Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment.

Materials And Methods: Intermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and F-choline-PET. F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation.

Results: Of 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUV and SUV tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml.

Conclusions: This is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.24234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839367PMC
February 2018

Initial FDG-PET/CT predicts survival in adults Ewing sarcoma family of tumors.

Oncotarget 2017 Sep 18;8(44):77050-77060. Epub 2017 Aug 18.

Nuclear Medicine Unit, ICO Cancer Center Gauducheau, Saint Herblain, France.

Purpose: The aim of this retrospective study was to determine, at baseline, the prognostic value of different FDG-PET/CT quantitative parameters in a homogenous Ewing Sarcoma Family of Tumors (ESFT) adult population, compared with clinically relevant prognostic factors.

Methods: Adult patients from 3 oncological centers, all with proved ESFT, were retrospectively included. Quantitative FDG-PET/CT parameters (SUV (maximum, peak and mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion of each patient were recorded before treatment, as well as usual clinical prognostic factors (stage of disease, location, tumor size, gender and age). Then, their relation with progression free survival (PFS) and overall survival (OS) was evaluated.

Results: 32 patients were included. Median age was 21 years (range, 15 to 61). Nineteen patients (59%) were initially metastatic. On multivariate analysis, high SUV remained independent predictor of worst OS (p=0.02) and PFS (p=0.019), metastatic disease of worst PFS (p=0.01) and high SUVpeak of worst OS (p=0.01). Optimal prognostic cut-off of SUV was found at 12.5 in multivariate analyses for PFS and OS (=0.0001).

Conclusions: FDG-PET/CT, recommended at ESFT diagnosis for initial staging, can be a useful tool for predicting long-term adult patients outcome through semi-quantitative parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.20335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652763PMC
September 2017

Voxel-based multimodel fitting method for modeling time activity curves in SPECT images.

Med Phys 2017 Dec 23;44(12):6280-6288. Epub 2017 Oct 23.

Inserm UMR1037, CRCT, Université Toulouse III-Paul Sabatier, F-31000, Toulouse, France.

Purpose: Estimating the biodistribution and the pharmacokinetics from time-sequence SPECT images on a per-voxel basis is useful for studying activity nonuniformity or computing absorbed dose distributions by convolution of voxel kernels or Monte-Carlo radiation transport. Current approaches are either region-based, thus assuming uniform activity within the region, or voxel-based but using the same fitting model for all voxels.

Methods: We propose a voxel-based multimodel fitting method (VoMM) that estimates a fitting function for each voxel by automatically selecting the most appropriate model among a predetermined set with Akaike criteria. This approach can be used to compute the time integrated activity (TIA) for all voxels in the image. To control fitting optimization that may fail due to excessive image noise, an approximated version based on trapezoid integration, named restricted method, is also studied. From this comparison, the number of failed fittings within images was estimated and analyzed. Numerical experiments were used to quantify uncertainties and feasibility was demonstrated with real patient data.

Results: Regarding numerical experiments, root mean square errors of TIA obtained with VoMM were similar to those obtained with bi-exponential fitting functions, and were lower (< 5% vs.  > 10%) than with single model approaches that consider the same fitting function for all voxels. Failure rates were lower with VoMM and restricted approaches than with single-model methods. On real clinical data, VoMM was able to fit 90% of the voxels and led to less failed fits than single-model approaches. On regions of interest (ROI) analysis, the difference between ROI-based and voxel-based TIA estimations was low, less than 4%. However, the computation of the mean residence time exhibited larger differences, up to 25%.

Conclusions: The proposed voxel-based multimodel fitting method, VoMM, is feasible on patient data. VoMM leads organ-based TIA estimations similar to conventional ROI-based method. However, for pharmacokinetics analysis, studies of spatial heterogeneity or voxel-based absorbed dose assessment, VoMM could be used preferentially as it prevents model overfitting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mp.12586DOI Listing
December 2017

A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma.

Clin Cancer Res 2016 Sep 8;22(17):4350-4355. Epub 2016 Apr 8.

INSERM UMR 892, CNRS UMR 6299, Université de Nantes, Nantes, France.

Purpose: Painful peripheral neuropathy is a frequent toxicity associated with bortezomib therapy. This study aimed to identify loci that affect susceptibility to this toxicity.

Experimental Design: A genome-wide association study (GWAS) of 370,605 SNPs was performed to identify risk variants for developing severe bortezomib-induced peripheral neuropathy (BiPN) in 469 patients with multiple myeloma who received bortezomib-dexamethasone therapy prior to autologous stem cell in randomized clinical trials of the Intergroupe Francophone du Myelome (IFM) and findings were replicated in 114 patients with multiple myeloma of the HOVON-65/GMMG-HD4 clinical trial.

Results: An SNP in the PKNOX1 gene was associated with BiPN in the exploratory cohort [rs2839629; OR, 1.89, 95% confidence interval (CI), 1.45-2.44; P = 7.6 × 10(-6)] and in the replication cohort (OR, 2.04; 95% CI, = 1.11-3.33; P = 8.3 × 10(-3)). In addition, rs2839629 is in strong linkage disequilibrium (r(2) = 0.87) with rs915854, located in the intergenic region between PKNOX1 and cystathionine-ß-synthetase (CBS) Expression quantitative trait loci mapping showed that both rs2839629 and rs915854 genotypes have an impact on PKNOX1 expression in nerve tissue, whereas rs2839629 affects CBS expression in skin and blood.

Conclusions: The use of GWAS in multiple myeloma pharmacogenomics has identified a novel candidate genetic locus mapping to PKNOX1 and in the immediate vicinity of CBS at 21q22.3 associated with the severe bortezomib-induced toxicity. The proximity of these two genes involved in neurologic pain whose tissue-specific expression is modified by the two variants provides new targets for neuroprotective strategies. Clin Cancer Res; 22(17); 4350-5. ©2016 AACR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-15-3163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010494PMC
September 2016

(90)Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study.

Lancet Haematol 2015 Mar 25;2(3):e108-17. Epub 2015 Feb 25.

Nuclear Medicine Department, Centre Hospitalo-Universitaire, Nantes, France; Centre de Recherche en Cancérologie Nantes Angers, Inserm U 892, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6299, France; Sciences de la vie et Santé, University of Nantes, Nantes, France; Nuclear Medicine Department, Institut de Cancérologie de l'Ouest-Gauducheau, saint-Herblain, France.

Background: Prognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study.

Methods: Adults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of (90)Y-DOTA-epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m(2) (92·5 MBq/m(2); level 1), 5·0 mCi/m(2) (185 MBq/m(2); level 2), 7·5 mCi/m(2) (277·5 MBq/m(2); level 3), and 10·0 mCi/m(2) (370 MBq/m(2); level 4). The primary objective was to identify the maximum tolerated dose of (90)Y-DOTA-epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457.

Findings: Between Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27-77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3-4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4).

Interpretation: (90)Y-DOTA-epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m(2) 1 week apart per cycle for phase 2 studies.

Funding: Immunomedics and Direction de la Recherche Clinique of Nantes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3026(15)00020-4DOI Listing
March 2015

Pharmacokinetics and Dosimetry Studies for Optimization of Pretargeted Radioimmunotherapy in CEA-Expressing Advanced Lung Cancer Patients.

Front Med (Lausanne) 2015 27;2:84. Epub 2015 Nov 27.

CNRS UMR 6299, Centre Régional de Recherche en Cancérologie Nantes/Angers (CRCNA), INSERM U892 , Nantes , France ; GIP Arronax , Saint-Herblain , France.

Objectives: A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096) was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA) to optimize bispecific antibody and labeled peptide doses, as well as the delay between their injections.

Methods: Three cohorts of three patients received the anti-CEA × anti-histamine-succinyl-glycine (HSG)-humanized trivalent bispecific antibody (TF2) and the IMP288 bivalent HSG peptide. Patients underwent a pretherapeutic imaging session S1 (44 or 88 nmol/m(2) of TF2 followed by 4.4 nmol/m(2), 185 MBq, of (111)In-labeled IMP288) and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m(2) of TF2 followed by 24 nmol/m(2), 1.1 GBq/m(2), of (177)Lu-labeled IMP288). The pretargeting delay was 24 or 48 h. The dose schedule was defined based on preclinical TF2 pharmacokinetic (PK) studies, on our previous clinical data using the previous anti-CEA-pretargeting system, and on clinical results observed in the first patients injected using the same system in Netherlands.

Results: TF2 PK was represented by a two-compartment model in which the central compartment volume (Vc) was linearly dependent on the patient's surface area. PK was remarkably similar, with a clearance of 0.33 ± 0.03 L/h/m(2). (111)In- and (177)Lu-IMP288 PK was also well represented by a two-compartment model. IMP288 PK was faster (clearance 1.4-3.3 L/h). The Vc was proportional to body surface area, and IMP288 clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modeling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumor activity PK was variable. Organ-absorbed doses were not significantly different in the three cohorts, but the tumor dose was significantly higher with the higher molar doses of TF2 (p < 0.002). S1 imaging predicted absorbed doses calculated in S2.

Conclusion: The best dosing parameters corresponded to the shorter pretargeting delay and to the highest TF2 molar doses. S1 imaging session accurately predicted PK as well as absorbed doses of S2, thus potentially allowing for patient selection and dose optimization.

Trial Registration: ClinicalTrials.gov NCT01221675 (EudractCT 200800603096).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2015.00084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661432PMC
December 2015

TestDose: A nuclear medicine software based on Monte Carlo modeling for generating gamma camera acquisitions and dosimetry.

Med Phys 2015 Dec;42(12):6885-94

UMR 1037 INSERM/UPS, CRCT, 133 Route de Narbonne, Toulouse 31062, France.

Purpose: The TestDose platform was developed to generate scintigraphic imaging protocols and associated dosimetry by Monte Carlo modeling. TestDose is part of a broader project (www.dositest.com) whose aim is to identify the biases induced by different clinical dosimetry protocols.

Methods: The TestDose software allows handling the whole pipeline from virtual patient generation to resulting planar and SPECT images and dosimetry calculations. The originality of their approach relies on the implementation of functional segmentation for the anthropomorphic model representing a virtual patient. Two anthropomorphic models are currently available: 4D XCAT and ICRP 110. A pharmacokinetic model describes the biodistribution of a given radiopharmaceutical in each defined compartment at various time-points. The Monte Carlo simulation toolkit gate offers the possibility to accurately simulate scintigraphic images and absorbed doses in volumes of interest. The TestDose platform relies on gate to reproduce precisely any imaging protocol and to provide reference dosimetry. For image generation, TestDose stores user's imaging requirements and generates automatically command files used as input for gate. Each compartment is simulated only once and the resulting output is weighted using pharmacokinetic data. Resulting compartment projections are aggregated to obtain the final image. For dosimetry computation, emission data are stored in the platform database and relevant gate input files are generated for the virtual patient model and associated pharmacokinetics.

Results: Two samples of software runs are given to demonstrate the potential of TestDose. A clinical imaging protocol for the Octreoscan™ therapeutical treatment was implemented using the 4D XCAT model. Whole-body "step and shoot" acquisitions at different times postinjection and one SPECT acquisition were generated within reasonable computation times. Based on the same Octreoscan™ kinetics, a dosimetry computation performed on the ICRP 110 model is also presented.

Conclusions: The proposed platform offers a generic framework to implement any scintigraphic imaging protocols and voxel/organ-based dosimetry computation. Thanks to the modular nature of TestDose, other imaging modalities could be supported in the future such as positron emission tomography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1118/1.4934828DOI Listing
December 2015

Single-Dose Anti-CD138 Radioimmunotherapy: Bismuth-213 is More Efficient than Lutetium-177 for Treatment of Multiple Myeloma in a Preclinical Model.

Front Med (Lausanne) 2015 4;2:76. Epub 2015 Nov 4.

Centre Régional de Recherche en Cancérologie Nantes/Angers (CRCNA) - UMR 892 INSERM, Université de Nantes , Nantes , France ; CNRS 6299, Université de Nantes , Nantes , France ; Université de Nantes , Nantes , France ; Institut de Cancérologie de l'Ouest , Saint-Herblain , France.

Objectives: Radioimmunotherapy (RIT) has emerged as a potential treatment option for multiple myeloma (MM). In humans, a dosimetry study recently showed the relevance of RIT using an antibody targeting the CD138 antigen. The therapeutic efficacy of RIT using an anti-CD138 antibody coupled to (213)Bi, an α-emitter, was also demonstrated in a preclinical MM model. Since then, RIT with β-emitters has shown efficacy in treating hematologic cancer. In this paper, we investigate the therapeutic efficacy of RIT in the 5T33 murine MM model using a new anti-CD138 monoclonal antibody labeled either with (213)Bi for α-RIT or (177)Lu for β-RIT.

Methods: A new monoclonal anti-CD138 antibody, 9E7.4, was generated by immunizing a rat with a murine CD138-derived peptide. Antibody specificity was validated by flow cytometry, biodistribution, and α-RIT studies. Then, a β-RIT dose-escalation assay with the (177)Lu-radiolabeled 9E7.4 mAb was performed in KalwRij C57/BL6 mice 10 days after i.v. engraftment with 5T33 MM cells. Animal survival and toxicological parameters were assessed to define the optimal activity.

Results: α-RIT performed with 3.7 MBq of (213)Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared to 37 days for the untreated control and effected cure in 45% of animals. β-RIT performed with 18.5 MBq of (177)Lu-labeled 9E7.4 mAb was well tolerated and significantly increased mouse survival (54 vs. 37 days in the control group); however, no mice were cured with this treatment.

Conclusion: This study revealed the advantages of α-RIT in the treatment of MM in a preclinical model where β-RIT shows almost no efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2015.00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631990PMC
November 2015

Assessment of Lymph Nodes and Prostate Status Using Early Dynamic Curves with (18)F-Choline PET/CT in Prostate Cancer.

Front Med (Lausanne) 2015 9;2:67. Epub 2015 Sep 9.

Department of Nuclear Medicine, ICO Cancer Center , Saint Herblain , France ; Centre Régional de Recherche en Cancérologie Nantes/Angers, U892, CNRS UMR 6299, INSERM , Nantes , France.

Introduction: Dynamic image acquisition with (18)F-Choline [fluorocholine (FCH)] PET/CT in prostate cancer is mostly used to overcome the bladder repletion, which could obstruct the loco-regional analysis. The aim of our study was to analyze early dynamic FCH acquisitions to define pelvic lymph node or prostate pathological status.

Material And Methods: Retrospective analysis was performed on 39 patients for initial staging (n = 18), or after initial treatment (n = 21). Patients underwent 10-min dynamic acquisitions centered on the pelvis, after injection of 3-4 MBq/kg of FCH. Whole-body images were acquired about 1 h after injection using a PET/CT GE Discovery LS (GE-LS) or Siemens Biograph mCT (mCT). Maximum and mean SUV according to time were measured on nodal and prostatic lesions. SUVmean was corrected for partial volume effect (PVEC) with suitable recovery coefficients. The status of each lesion was based on histological results or patient follow-up (>6 months). A Mann-Whitney test and ANOVA were used to compare mean and receiver operating characteristic (ROC) curve analysis.

Results: The median PSA was 8.46 ng/mL and the median Gleason score was 3 + 4. Ninety-two lesions (43 lymph nodes and 49 prostate lesions) were analyzed, including 63 malignant lesions. In early dynamic acquisitions, the maximum and mean SUV were significantly higher, respectively, on mCT and GE-LS, in malignant versus benign lesions (p < 0.001, p < 0.001). Mean SUV without PVEC, allowed better discrimination of benign from malignant lesions, in comparison with maximum and mean SUV (with PVEC), for both early and late acquisitions. For patients acquired on mCT, area under the ROC curve showed a trend to better sensitivity and specificity for early acquisitions, compared with late acquisitions (SUVmax AUC 0.92 versus 0.85, respectively).

Conclusion: Assessment of lymph nodes and prostate pathological status with early dynamic imaging using PET/CT FCH allowed prostate cancer detection in situations where proof of malignancy is difficult to obtain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2015.00067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563255PMC
October 2015

Radioimmunoconjugates for the treatment of cancer.

Semin Oncol 2014 Oct 22;41(5):613-22. Epub 2014 Jul 22.

Centre de Recherche en Cancérologie de Nantes-Angers, Inserm, Université de Nantes, Nantes, France; Department of Nuclear Medicine, ICO-René Gauducheau, Saint-Herblain, France.

Radioimmunotherapy (RIT) has been developed for more than 30 years. Two products targeting the CD20 antigen are approved in the treatment of non-Hodgkin B-cell lymphoma (NHBL): iodine 131-tositumomab and yttrium 90-ibritumomab tiuxetan. RIT can be integrated in clinical practice for the treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy. High-dose treatment, RIT in first-line treatment, fractionated RIT, and use of new humanized monoclonal antibodies (MAbs), in particular targeting CD22, showed promising results in NHBL. In other hemopathies, such as multiple myeloma, efficacy has been demonstrated in preclinical studies. In solid tumors, more resistant to radiation and less accessible to large molecules such as MAbs, clinical efficacy remains limited. However, pretargeting methods have shown clinical efficacy. Finally, new beta emitters such as lutetium 177, with better physical properties will further improve the safety of RIT and alpha emitters, such as bismuth 213 or astatine 211, offer the theoretical possibility to eradicate the last microscopic clusters of tumor cells, in the consolidation setting. Personalized treatments, based on quantitative positron emission tomography (PET), pre-therapeutic imaging, and dosimetry procedures, also could be applied to adapt injected activity to each patient.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.seminoncol.2014.07.004DOI Listing
October 2014

Radioimmunotherapy of B-Cell Non-Hodgkin's Lymphoma.

Front Oncol 2013 11;3:177. Epub 2013 Jul 11.

Nuclear Medicine Department, University Hospital , Nantes , France ; CRCNA, INSERM U892, CNRS UMR 7299, Université de Nantes, IRS-UN , Nantes , France.

This manuscript reviews current advances in the use of radioimmunotherapy (RIT) for the treatment of B-cell non-Hodgkin's lymphoma (NHL). RIT has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (MAbs), and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved: (131)I-tositumomab (Bexxar(®)), and (90)Y-ibritumomab tiuxetan (Zevalin(®)). (131)I-tositumomab is available in the United States, and (90)Y-ibritumumab tiuxetan in Europe, the United States, Asia, and Africa. RIT can be integrated in clinical practice using non-ablative activities for treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy in front-line treatment in FL patients. Despite the lack of phase III studies to clearly define the efficacy of RIT in the management of B lymphoma in the era of rituximab-based therapy, RIT efficacy in NHL has been demonstrated. In relapsing refractory FL and transformed NHL, RIT as a monotherapy induces around 30% complete response with a possibility of durable remissions. RIT consolidation after induction therapy significantly improves the quality of the response. Dose-limiting toxicity of RIT is hematological, depending on bone marrow involvement and prior treatment. Non-hematological toxicity is generally low. Different studies have been published assessing innovative protocols of RIT or new indications, in particular treatment in patients with aggressive lymphomas. High-dose treatment, RIT as consolidation after different therapeutic induction modalities, RIT in first-line treatment or fractionated RIT showed promising results. New MAbs, in particular humanized MAbs, or combinations of naked and radiolabeled MAbs, also appear promising. Personalized dosimetry protocols should be developed to determine injected activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2013.00177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708100PMC
July 2013

Calibration test of PET scanners in a multi-centre clinical trial on breast cancer therapy monitoring using 18F-FLT.

PLoS One 2013 13;8(3):e58152. Epub 2013 Mar 13.

Department of Nuclear Medicine, Academic Hospital, Angers, France.

Unlabelled: A multi-centre trial using PET requires the analysis of images acquired on different systems We designed a multi-centre trial to estimate the value of 18F-FLT-PET to predict response to neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. A calibration check of each PET-CT and of its peripheral devices was performed to evaluate the reliability of the results.

Material And Methods: 11 centres were investigated. Dose calibrators were assessed by repeated measurements of a 68Ge certified source. The differences between the clocks associated with the dose calibrators and inherent to the PET systems were registered. The calibration of PET-CT was assessed with an homogeneous cylindrical phantom by comparing the activities per unit of volume calculated from the dose calibrator measurements with that measured on 15 Regions of Interest (ROIs) drawn on 15 consecutive slices of reconstructed filtered back-projection (FBP) images. Both repeatability of activity concentration based upon the 15 ROIs (ANOVA-test) and its accuracy were evaluated.

Results: There was no significant difference for dose calibrator measurements (median of difference -0.04%; min = -4.65%; max = +5.63%). Mismatches between the clocks were less than 2 min in all sites and thus did not require any correction, regarding the half life of 18F. For all the PET systems, ANOVA revealed no significant difference between the activity concentrations estimated from the 15 ROIs (median of difference -0.69%; min = -9.97%; max = +9.60%).

Conclusion: No major difference between the 11 centres with respect to calibration and cross-calibration was observed. The reliability of our 18F-FLT multi-centre clinical trial was therefore confirmed from the physical point of view. This type of procedure may be useful for any clinical trial involving different PET systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058152PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596383PMC
September 2013

Assessment of acquisition protocols for routine imaging of Y-90 using PET/CT.

EJNMMI Res 2013 Feb 17;3(1):11. Epub 2013 Feb 17.

Nuclear Medicine Department, University Hospital of Nantes, Place Alexis Ricordeau, Nantes, 44093, France.

Background: Despite the early theoretical prediction of the 0+-0+ transition of 90Zr, 90Y-PET underwent only recently a growing interest for the development of imaging radioembolization of liver tumors. The aim of this work was to determine the minimum detectable activity (MDA) of 90Y by PET imaging and the impact of time-of-flight (TOF) reconstruction on detectability and quantitative accuracy according to the lesion size.

Methods: The study was conducted using a Siemens Biograph® mCT with a 22 cm large axial field of view. An IEC torso-shaped phantom containing five coplanar spheres was uniformly filled to achieve sphere-to-background ratios of 40:1. The phantom was imaged nine times in 14 days over 30 min. Sinograms were reconstructed with and without TOF information. A contrast-to-noise ratio (CNR) index was calculated using the Rose criterion, taking partial volume effects into account. The impact of reconstruction parameters on quantification accuracy, detectability, and spatial localization of the signal was investigated. Finally, six patients with hepatocellular carcinoma and four patients included in different 90Y-based radioimmunotherapy protocols were enrolled for the evaluation of the imaging parameters in a clinical situation.

Results: The highest CNR was achieved with one iteration for both TOF and non-TOF reconstructions. The MDA, however, was found to be lower with TOF than with non-TOF reconstruction. There was no gain by adding TOF information in terms of CNR for concentrations higher than 2 to 3 MBq mL-1, except for infra-centimetric lesions. Recovered activity was highly underestimated when a single iteration or non-TOF reconstruction was used (10% to 150% less depending on the lesion size). The MDA was estimated at 1 MBq mL-1 for a TOF reconstruction and infra-centimetric lesions. Images from patients treated with microspheres were clinically relevant, unlike those of patients who received systemic injections of 90Y.

Conclusions: Only one iteration and TOF were necessary to achieve an MDA around 1 MBq mL-1 and the most accurate localization of lesions. For precise quantification, at least three iterations gave the best performance, using TOF reconstruction and keeping an MDA of roughly 1 MBq mL-1. One and three iterations were mandatory to prevent false positive results for quantitative analysis of clinical data.

Trial Registration: http://IDRCB 2011-A00043-38 P101103.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/2191-219X-3-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614476PMC
February 2013

Dosimetry results suggest feasibility of radioimmunotherapy using anti-CD138 (B-B4) antibody in multiple myeloma patients.

Tumour Biol 2012 Jun 3;33(3):679-88. Epub 2012 Mar 3.

Nuclear Medicine Department, Comprehensive Cancer Center ICO Gauducheau, IRCNA, Saint Herblain, France.

Syndecan-1 (CD138), a heparan sulfate proteoglycan, is constantly expressed on tumor cells in multiple myeloma (MM). This surface antigen is an attractive candidate for targeted therapy, especially radioimmunotherapy (RAIT). We report preliminary biodistribution and dosimetry results obtained in refractory MM patients in a phase I/II RAIT study using iodine-131-labeled anti-CD138 (B-B4) monoclonal antibody (mAb). Four patients with progressive disease were enrolled after three lines of therapy. They received 370 MBq (20 mg/m(2)) of (131)I-B-B4 for the dosimetry study. Each patient underwent a whole body (WB) CT and four WB emission scans at days D0, D1, and D3-4. Images were corrected for attenuation and scatter to assess doses absorbed by organs and bone marrow (BM). Blood and urine samples were additionally collected. Dosimetry was conducted using the MIRD method. Images obtained 1 h after (131)I-B-B4 injection showed high BM and liver uptake without kidney uptake. The BM uptake confirmed BM involvement as detected by pre-inclusion FDG PET/CT. Absorbed doses were calculated at 2.03 ± 0.3 mGy/MBq for the liver, 1.10 ± 0.9 mGy/MBq for the kidneys, and 0.52 ± 0.20 mGy/MBq for the BM. Grade III thrombocytopenia was documented in two cases (highest BM-absorbed doses), and no grade IV hematological toxicity was observed. Therefore, autologous stem cells were not infused. One patient out of four experienced partial response, with 60% reduction of M-spike on serum electrophoresis, and total relief of pain, lasting for 1 year. This patient was able to go back to work. In this proof of concept study based on dosimetry, we show that MM RAIT is feasible using the anti-CD138 antibody. It would be of great interest to perform a RAIT phase I/II trial with a humanized anti-CD138 mAb with increased doses and systematic autologous stem cell infusions to overcome hematological toxicity and achieve efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13277-012-0362-yDOI Listing
June 2012

FDG PET evaluation of early axillary lymph node response to neoadjuvant chemotherapy in stage II and III breast cancer patients.

Eur J Nucl Med Mol Imaging 2011 Jun 10;38(6):1029-36. Epub 2011 Feb 10.

Nuclear Medicine Department, Comprehensive Cancer Center René Gauducheau, IRCNA, Saint Herblain, France.

Purpose: Regional axillary lymph node status has remained the single most independent variable to predict prognosis both in terms of disease recurrence and survival. This study aimed to prospectively assess sequential [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) findings as early predictors of axillary lymph node response to neoadjuvant chemotherapy in stage II and III breast cancer patients.

Methods: Images were acquired with a PET/CT scanner in 52 patients after administration of FDG (5 MBq/kg) at baseline and after the first, second, third and sixth course of chemotherapy before surgery. Clinical examination and ultrasound (US) were used to assess the size of axillary nodes. Decrease in the standardized uptake value (SUV) with PET corrected or not for partial volume effects was compared to the pathological response.

Results: The sensitivity, specificity and accuracy of axillary node staging was higher with PET (75, 87 and 80%) than with US (50, 83 and 65%), and even more so when PET images were corrected for partial volume effects (86, 83 and 84%). While FDG uptake did not vary much in non-responders, as confirmed by histopathological analysis, it markedly decreased to baseline levels in responders (p < 10(-5)). Fifty per cent of baseline SUV was considered the best cutoff value to distinguish responders from non-responders. The sensitivity, specificity, negative predictive value and accuracy of FDG PET after one course of chemotherapy were, respectively, 96, 75, 95 and 84%.

Conclusion: The pathological status of regional axillary lymph nodes in stage II and III breast cancer patients could be accurately predicted after one course of neoadjuvant chemotherapy based on FDG PET images.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-011-1735-yDOI Listing
June 2011

Three methods assessing red marrow dosimetry in lymphoma patients treated with radioimmunotherapy.

Cancer 2010 Feb;116(4 Suppl):1093-100

Medical Physics Department, CLCC Gauducheau, St Herblain, France.

Background: Maximum injected activity in radioimmunotherapy (RIT) is limited by bone marrow toxicity. Many dosimetric approaches have been proposed, leading to high variability in the results and elusive absorbed dose-effect relations. This study presents the results of red marrow (RM) absorbed dose estimates performed with 3 methods.

Methods: Five patients received 2 co-infusions of (90)Y-labeled (370 MBq/m2) and (111)In- labeled (120 MBq) epratuzumab (1.5 mg/kg) 1 week apart. RM-absorbed dose was estimated by 3 methodologies. The first approach (M1) used L(2)-L(4) lumbar vertebrae imaging. M2 and M3 methods used different red marrow to blood ratios (RMBLR) to assess RM-absorbed dose. RMBLR was set to a fixed value of 0.36 in M2 or assessed according to each patient's hematocrit in M3.

Results: Median RM-absorbed doses were 4.1 (2.9-8.4), 2.3 (2.0-2.7), and 2.3 (1.6-2.5) mGy/MBq for M1, M2, and M3, respectively. No trend could be found between total RM-absorbed dose and toxicity for M2 and M3. Conversely, M1 seemed to provide the best absorbed dose-effect relation. The 4 patients with the highest RM-absorbed doses exhibited grade 4 toxicity. The fifth patient, with the lowest RB absorbed dose, exhibited only a mild (grade 2) toxicity.

Conclusions: Image-based methodology (M1) seems to better predict hematological toxicity as compared with blood-based methods. Only this method provides for bone marrow involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.24797DOI Listing
February 2010

Comparison of electron dose-point kernels in water generated by the Monte Carlo codes, PENELOPE, GEANT4, MCNPX, and ETRAN.

Cancer Biother Radiopharm 2009 Aug;24(4):461-7

Department of Radiation Physics, University of Gothenburg , Göteborg, Sweden.

Point kernels describe the energy deposited at a certain distance from an isotropic point source and are useful for nuclear medicine dosimetry. They can be used for absorbed-dose calculations for sources of various shapes and are also a useful tool when comparing different Monte Carlo (MC) codes. The aim of this study was to compare point kernels calculated by using the mixed MC code, PENELOPE (v. 2006), with point kernels calculated by using the condensed-history MC codes, ETRAN, GEANT4 (v. 8.2), and MCNPX (v. 2.5.0). Point kernels for electrons with initial energies of 10, 100, 500, and 1 MeV were simulated with PENELOPE. Spherical shells were placed around an isotropic point source at distances from 0 to 1.2 times the continuous-slowing-down-approximation range (R(CSDA)). Detailed (event-by-event) simulations were performed for electrons with initial energies of less than 1 MeV. For 1-MeV electrons, multiple scattering was included for energy losses less than 10 keV. Energy losses greater than 10 keV were simulated in a detailed way. The point kernels generated were used to calculate cellular S-values for monoenergetic electron sources. The point kernels obtained by using PENELOPE and ETRAN were also used to calculate cellular S-values for the high-energy beta-emitter, 90Y, the medium-energy beta-emitter, 177Lu, and the low-energy electron emitter, 103mRh. These S-values were also compared with the Medical Internal Radiation Dose (MIRD) cellular S-values. The greatest differences between the point kernels (mean difference calculated for distances, <0.9 r/R(CSDA)), using PENELOPE and those from ETRAN, GEANT4, and MCNPX, were 3.6%, 6.2%, and 14%, respectively. The greatest difference between the cellular S-values for monoenergetic electrons was 1.4%, 2.5%, and 6.9% for ETRAN, GEANT4, and MCNPX, respectively, compared to PENELOPE, if omitting the S-values when the activity was distributed on the cell surface for 10-keV electrons. The largest difference between the cellular S-values for the radionuclides, between PENELOPE and ETRAN, was seen for 177Lu (1.2%). There were large differences between the MIRD cellular S-values and those obtained from PENELOPE: up to 420% for monoenergetic electrons and <22% for the radionuclides, with the largest difference for 103mRh. In conclusion, differences were found between the point kernels generated by different MC codes, but these differences decreased when cellular S-values were calculated, and decreased even further when the energy spectra of the radionuclides were taken into consideration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/cbr.2008.0573DOI Listing
August 2009
-->