Publications by authors named "Florian C Gaertner"

44 Publications

Estimating the Potential of Radiomics Features and Radiomics Signature from Pretherapeutic PSMA-PET-CT Scans and Clinical Data for Prediction of Overall Survival When Treated with Lu-PSMA.

Diagnostics (Basel) 2021 Jan 28;11(2). Epub 2021 Jan 28.

Department of Nuclear Medicine, University Hospital Bonn, 53127 Bonn, Germany.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PSMA-PET/CT) scans can facilitate diagnosis and treatment of prostate disease. Radiomics signature (RS) is widely used for the analysis of overall survival (OS) in cancer diseases. This study aims at investigating the role of radiomics features (RFs) and RS from pretherapeutic gallium-68 (Ga)-PSMA-PET/CT findings and patient-specific clinical parameters to analyze overall survival of prostate cancer (PC) patients when treated with lutethium-177 (Lu)-PSMA. A cohort of 83 patients with advanced PC was retrospectively analyzed. Average values of 73 RFs of 2070 malignant hotspots as well as 22 clinical parameters were analyzed for each patient. From the Cox proportional hazard model, the least absolute shrinkage and selection operator (LASSO) regularization method is used to select most relevant features (standardized uptake value (SUV) and kurtosis with the coefficients of 0.984 and -0.118, respectively) and to calculate the RS from the RFs. Kaplan-Meier (KM) estimator was used to analyze the potential of RFs and conventional clinical parameters, such as metabolic tumor volume (MTV) and standardized uptake value (SUV) for the prediction of survival. As a result, SUV, kurtosis, the calculated RS, SUV, as well as Hemoglobin (Hb)1, C-reactive protein (CRP)1, and ECOG1 (clinical parameters) achieved -values less than 0.05, which suggest the potential of findings from Ga-PSMA-PET/CT scans as well as patient-specific clinical parameters for the prediction of OS for patients with advanced PC treated with Lu-PSMA therapy.
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http://dx.doi.org/10.3390/diagnostics11020186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912143PMC
January 2021

Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status.

J Alzheimers Dis 2021 ;79(2):493-509

German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald.

Background: Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework.

Objective: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.

Methods: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB).

Results: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups).

Conclusion: While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.
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http://dx.doi.org/10.3233/JAD-200472DOI Listing
September 2021

Sialoscintigraphy - Shopworn or Bestselling? A Traditional Procedure with New Prominent Role in Theranostics and Immuno-Oncology.

Nuklearmedizin 2020 Sep 18;59(5):375-380. Epub 2020 May 18.

Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.

Sialoscintigraphy has been used in nuclear imaging for almost sixty years. It allows functional assessment and quantification of all large salivary glands. Physiological function of the salivary glands is essential for the preservation of the oral mucosa, the sense of taste and dental health. Impaired salivary gland function may lead to reduced or even absent salivation resulting in various complaints such as loss of taste reducing quality of life. During the recent years clinical relevance of assessment of salivary gland function has been rising. As novel radiopharmaceuticals such as 225Ac-PSMA or 177Lu-PSMA may cause damage to the salivary glands in a subset of patients, reliable methods for quantification of salivary gland function are vital for therapy planning and follow-up. Standardized protocols for the implementation and interpretation of this procedure are necessary to achieve comparable results from individual theranostic centers and to facilitate multicenter trials. Sialocintigraphy is also of clinical relevance for immunooncology. Treatments with checkpoint inhibitors such as Ipilimumab or Nivulomab frequently cause autoimmune disorders affecting the salivary glands that may lead to reduced production of saliva and finally loss of taste. Therefore, standardized procedure protocols for sialoscintigraphy are also important for general oncology.Here we suggest a protocol for sialoscintigraphy that may be used as standard in centers for theranostics or immunooncology and discuss the potential future role of this traditional procedure.
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http://dx.doi.org/10.1055/a-1152-2279DOI Listing
September 2020

Systemic Therapy of Neuroendocrine Neoplasia: Single Center Experience from a Cohort of 110 Consecutive Cases.

Int J Endocrinol 2020 31;2020:1491475. Epub 2020 Jan 31.

Department of Internal Medicine 3, Center of Integrated Oncology Aachen-Bonn-Cologne-Duesseldorf, University Hospital of Bonn, Bonn, Germany.

Objective: Neuroendocrine neoplasias (NENs) represent a rare and biologically heterogeneous group of malignancies. Treatment of NEN patients remains challenging due to lack of prospective evidence on the choice of ideal therapeutic sequence and therapeutic efficacy in specific individual scenarios.

Methods: Clinical data on 110 consecutive patients suffering from NEN treated at a single German university center were analyzed, therapeutic regimens applied were assessed, and the outcome was evaluated.

Results: Histological grading, Ki67 proliferation index, functional activity, and presence of metastases were identified as prognostic markers. 10-year overall survival rates were 92%, 44%, and 0% for G1, G2, and G3 tumors, and 60%, 39%, 69%, 53%, and 0% for Ki67 <2%, 3-5%, 6-20%, 21-49%, and >50%, respectively. Peptide receptor radionuclide therapy (PRRT) and cytostatic chemotherapy were the second most common options, with PRRT being used more frequently in NET G1 and G2 and chemotherapy in NEC G3. Combination chemotherapy with etoposide plus cisplatin or carboplatin showed disease control rates (DCRs) of overall 74%, with a short median progression-free survival (PFS) of 7 or 5 months, respectively. DCR and PFS for PRRT were 89% and 22 months when administered as monotherapy, versus 100% and 27 months upon combination with somatostatin analog (SSA) therapy. Of note, PRRT also achieved disease control as best response in 5/5 (100%) selected cases of NEC G3.

Conclusion: Further prospective studies are warranted to help stratify available options for therapeutic intervention in NEN patients.
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http://dx.doi.org/10.1155/2020/1491475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013359PMC
January 2020

Biodistribution and post-therapy dosimetric analysis of [Lu]Lu-DOTA in patients with osteoblastic metastases: first results.

EJNMMI Res 2019 Nov 28;9(1):102. Epub 2019 Nov 28.

Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.

Background: Preclinical biodistribution and dosimetric analysis of [Lu]Lu-DOTA suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [Lu]Lu-DOTA in patients with metastatic skeletal disease.

Method: Four patients with metastatic skeletal disease (age range, 64-83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [Lu]Lu-DOTA. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier's dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose.

Results: Qualitative biodistribution analysis revealed early and high uptake of [Lu]Lu-DOTA in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [Lu]Lu-DOTA are consistent with preclinical data.

Conclusion: [Lu]Lu-DOTA shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [Lu]Lu-DOTA in the clinical setting.
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http://dx.doi.org/10.1186/s13550-019-0566-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882969PMC
November 2019

Diagnosis of peri-prosthetic loosening of total hip and knee arthroplasty using F-Fluoride PET/CT.

Oncotarget 2019 Mar 15;10(22):2203-2211. Epub 2019 Mar 15.

Clinic for Nuclear Medicine, University of Bonn, Bonn, Germany.

Periprosthetic loosening, either aseptic or induced by periprosthetic joint infection remains a major long term complication and challenge in orthopedics and trauma surgery. Sensitivity of potential loosening of the material and other causes of a painful prosthesis is essential for choosing the respective treatment option and providing the needed resources. F-Fluoride is a radiopharmaceutical which shows a high affinity to bone and a rapid blood clearance. The objective of this study was to assess F-Fluoride PET/CT´s sensitivity and specificity in diagnosing periprosthetic loosening in total hip and knee arthroplasty. We included 26 patients with 24 hip and 13 knee prostheses in our retrospective study with radiological or clinical suspicion of peri-prosthetic loosening at least one year after implantation. Results of F-Fluoride PET/CT imaging were compared with surgical results or clinical follow-up if surgery was not performed. On the basis of our data we found a sensitivity of 95.00 %, a specificity of 87.04 % and an accuracy of 89.19 % for F-Fluoride PET/CT. The results of our study show that F-Fluoride PET/CT is a useful and promising technique in diagnosing periprosthetic loosening of total hip and knee arthroplasties. Further investigation should focus on different uptake patterns of the isotope in periprosthetic joint infection and therefore distinguishing aseptic from septic loosening and enhancing the diagnostic value of this imaging method.
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http://dx.doi.org/10.18632/oncotarget.26762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481340PMC
March 2019

Peptide Receptor Radionuclide Therapy Combined With Chemotherapy in Patients With Neuroendocrine Tumors.

Clin Nucl Med 2019 May;44(5):e329-e335

From the Departments of Nuclear Medicine and.

Purpose: Combinations of therapies may enhance therapeutic effects without significantly increasing the incidence of adverse events. However, there are few data regarding survival after concomitant chemotherapy and peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-octreotate in patients with neuroendocrine tumors (NETs). Thus, we explored the outcome of this combination of therapies.

Methods: Fifteen patients with somatostatin receptor-positive, rapidly progressive G2/G3 NETs during chemotherapy or PRRT alone from 2 German cancer centers were included in the retrospective analysis. The patients received a combination of PRRT and chemotherapy with temozolomide (n = 3) or temozolomide plus capecitabine (n = 12). To evaluate the effects of the combined treatment, we assessed the responses, survival, and adverse events.

Results: The cumulative administered activity of [Lu]Lu-octreotate had a median of 21.3 GBq after 3 cycles of combination therapy. The patients exhibited a median progression-free survival of 7.1 months and a median overall survival of 25.3 months. The clinical benefit (objective response and stable disease) rates were as follows: 55% of patients according to CT, 38% in [F]F-FDG PET/CT, and 44% in [Ga]Ga-DOTATOC PET/CT. One patient with rapidly progressing liver metastases experienced grade 4 liver failure according to the Common Terminology Criteria for Adverse Events (version 5.0). Four other patients (27%) experienced significantly elevated (grade 3) liver parameters.

Conclusions: According to different imaging modalities, the combination of PRRT and temozolomide +/- capecitabine led to disease control in 38% to 55% of the progressive NETs after PRRT or chemotherapy alone failed. The overall survival in this extensively pretreated group of patients was nearly 25 months. The majority of patients did not experience any serious adverse events.
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http://dx.doi.org/10.1097/RLU.0000000000002532DOI Listing
May 2019

Preliminary results of biodistribution and dosimetric analysis of [Ga]Ga-DOTA: a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases.

Ann Nucl Med 2019 Jun 15;33(6):404-413. Epub 2019 Mar 15.

Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.

Objective: Pre-clinical studies with gallium-68 zoledronate ([Ga]Ga-DOTA) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [Lu]Lu-DOTA and [Ac]Ac-DOTA. This study aims to be the first human biodistribution and dosimetric analysis of [Ga]Ga-DOTA.

Methods: Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190 MBq (4.05-5.14 mCi) of [Ga]Ga-DOTA i.v. Biodistribution of [Ga]Ga-DOTA was studied with PET/CT initial dynamic imaging for 30 min; list mode over abdomen (reconstructed as six images of 300 s) followed by static (skull to mid-thigh) imaging at 45 min and 2.5 h with Siemens Biograph 2 PET/CT camera. Also, blood samples (8 time points) and urine samples (2 time points) were collected over a period of 2.5 h. Total activity (MBq) in source organs was determined using interview fusion software (MEDISO Medical Imaging Systems, Budapest, Hungary). A blood-based method for bone marrow self-dose determination and a trapezoidal method for urinary bladder contents residence time calculation were used. OLINDA/EXM version 2.0 software (Hermes Medical Solutions, Stockholm, Sweden) was used to generate residence times for source organs, organ absorbed doses and effective doses.

Results: High uptake in skeleton as target organ, kidneys and urinary bladder as organs of excretion and faint uptake in liver, spleen and salivary glands were seen. Qualitative and quantitative analysis supported fast blood clearance, high bone to soft tissue and lesion to normal bone uptake with [Ga]Ga-DOTA. Urinary bladder with the highest absorbed dose of 0.368 mSv/MBq presented the critical organ, followed by osteogenic cells, kidneys and red marrow receiving doses of 0.040, 0.031 and 0.027 mSv/MBq, respectively. The mean effective dose was found to be 0.0174 mSv/MBq which results in an effective dose of 2.61 mSv from 150 MBq.

Conclusions: Biodistribution of [Ga]Ga-DOTA was comparable to [F]NaF, [Tc]Tc-MDP and [Ga]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [F]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [Lu]Lu-DOTA and [Ac]Ac-DOTA.
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http://dx.doi.org/10.1007/s12149-019-01348-7DOI Listing
June 2019

Outcome and safety of rechallenge [Lu]Lu-PSMA-617 in patients with metastatic prostate cancer.

Eur J Nucl Med Mol Imaging 2019 May 24;46(5):1073-1080. Epub 2018 Nov 24.

Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.

Background: Data are sparse regarding the feasibility of radioligand therapy (RLT) with [Lu]Lu-PSMA-617 as a retreatment. We aimed to assess the outcome and safety of rechallenge PSMA-RLT in patients with progressive prostatic cancer who previously benefited from this therapy.

Materials And Methods: Patients who received rechallenge therapy at our department from January 2015 to March 2018 were assessed. Non-haematological and haematological adverse events were evaluated from laboratory data and clinical reports and were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Time to prostate-specific-antigen (PSA) progression and the overall survival (OS) rate of the study patients were calculated from the date of the first rechallenge cycle. Furthermore, the OS calculated from the first cycle baseline PSMA-RLT was compared with the survival of patients who received only baseline PSMA-RLT. The response data were determined using [Ga]Ga-PSMA-PET/CT and measurements of the tumour marker PSA.

Results: Included in this retrospective study were 30 patients who were initially treated with a median of 3 cycles (range 1-5) of PSMA-RLT and were eventually retreated after a median of 6 months (range 2-26). Each patient received a median of 3 (range 1-6) rechallenge cycles. None of the patients experienced a disabling or life-threatening grade 4 adverse event according to the Common Toxicity Criteria (CTC). Grade 3 toxicity occurred in 8 patients (27%). Serious adverse events included leucopoenia (n = 2), neutropoenia (n = 1), anaemia (n = 4), thrombopenia (n = 4) and elevated renal parameters (n = 1). Irreversible adverse events occurred in 21 patients (70%). The permanent adverse events were mild/moderate (CTC grade 1/2) in 19 patients and serious (CTC grade 3) in two patients, respectively. According to PSA measurements, 75-90% of patients showed a benefit (response/stable) from the first 4 rechallenge cycles. The median OS was 12 months calculated from the first rechallenge cycle and 25 months calculated from the first cycle baseline PSMA-RLT. For comparison, the median OS in patients who received only baseline PSMA-RLT was 9 months. The difference according to the logrank test was significant: p value <0.001. Patients with a PSA decrease after the first cycle of rechallenge PSMA-RLT survived a median of 19 months, while patients with a PSA increase survived only 6 months.

Conclusion: Rechallenge prostate-specific membrane antigen (PSMA) therapy has an acceptable safety profile. The majority of the retreated patients benefited from the rechallenge therapy. Patients who showed a biochemical response achieved a longer OS compared to patients who did not respond. The median OS was significantly longer in patients after rechallenge PSMA-RLT than in patients who received only baseline PSMA-RLT.
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http://dx.doi.org/10.1007/s00259-018-4222-xDOI Listing
May 2019

Role of textural heterogeneity parameters in patient selection for 177Lu-PSMA therapy via response prediction.

Oncotarget 2018 Sep 7;9(70):33312-33321. Epub 2018 Sep 7.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

Purpose: Prostate cancer is most common tumor in men causing significant patient mortality and morbidity. In newer diagnostic/therapeutic agents PSMA linked ones are specifically important. Analysis of textural heterogeneity parameters is associated with determination of innately aggressive and therapy resistant cell lines thus emphasizing their importance in therapy planning. The objective of current study was to assess predictive ability of tumor textural heterogeneity parameters from baseline Ga-PSMA PET prior to Lu-PSMA therapy.

Results: Entropy showed a negative correlation (r = -0.327, = 0.006, AUC = 0.695) and homogeneity showed a positive correlation (r = 0.315, = 0.008, AUC = 0.683) with change in pre and post therapy PSA levels.

Conclusions: Study showed potential for response prediction through baseline PET scan using textural features. It suggested that increase in heterogeneity of PSMA expression seems to be associated with an increased response to PSMA radionuclide therapy.

Materials And Methods: Retrospective analysis of 70 patients was performed. All patients had metastatic prostate cancer and were planned to undergo Lu-PSMA therapy. Pre-therapeutic Ga- PSMA PET scans were used for analysis. 3D volumes (VOIs) of 3 lesions each in bones and lymph nodes were manually delineated in static PET images. Five PET based textural heterogeneity parameters (COV, entropy, homogeneity, contrast, size variation) were determined. Results obtained were then compared with clinical parameters including pre and post therapy PSA, alkaline phosphate, bone specific alkaline phosphate levels and ECOG criteria. Spearman correlation was used to determine statistical dependence among variables. ROC analysis was performed to estimate the optimal cutoff value and AUC.
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http://dx.doi.org/10.18632/oncotarget.26051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161784PMC
September 2018

Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

Clin Nucl Med 2018 Jul;43(7):486-491

Institute of Nuclear Chemistry, Johannes Gutenberg University Mainz, Mainz, Germany.

In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma.

Methods: Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body.

Results: The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients).

Conclusions: [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum permissible activity in patients scheduled for therapy with [Lu]Lu-PSMA-617.
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http://dx.doi.org/10.1097/RLU.0000000000002102DOI Listing
July 2018

[44Sc]Sc-PSMA-617 Biodistribution and Dosimetry in Patients With Metastatic Castration-Resistant Prostate Carcinoma.

Clin Nucl Med 2018 May;43(5):323-330

Aim: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients.

Methods: Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection. Time-dependent changes in percentage activity in source organs (kidneys, bladder, salivary glands, small intestine, liver, spleen, and whole body) were determined. Bone marrow and urinary bladder contents residence time were also calculated. Source organs residence time, organ-absorbed doses, and effective doses were determined using OLINDA/EXM software.

Results: Physiological tracer uptake was seen in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and in metastases. Kidneys with highest radiation absorbed dose of 3.19E-01 mSv/MBq were the critical organs, followed by urinary bladder wall (2.24E-01 mSv/MBq, spleen [1.85E-01], salivary glands [1.11E-01], and liver [1.07E-01] mSv/MBq). Red marrow dose was found to be 3.31E-02 mSv/MBq. The mean effective dose of 3.89E-02 mSv/MBq and effective dose of 1.95 mSv was estimated from 50 MBq (treatment planning dose) of [Sc]Sc-PSMA-617.

Conclusions: [Sc]Sc-PSMA-617 is found to be a very promising radiopharmaceutical that can be used for pre [Lu]Lu-PSMA-617 therapeutic dosimetric assessment.
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http://dx.doi.org/10.1097/RLU.0000000000002003DOI Listing
May 2018

Ga-PSMA-PET/CT imaging of localized primary prostate cancer patients for intensity modulated radiation therapy treatment planning with integrated boost.

Eur J Nucl Med Mol Imaging 2018 07 21;45(7):1170-1178. Epub 2018 Feb 21.

Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.

Purpose: The purpose of our study was to show the feasibility and potential benefits of using Ga-PSMA-PET/CT imaging for radiation therapy treatment planning of patients with primary prostate cancer using either integrated boost on the PET-positive volume or localized treatment of the PET-positive volume. The potential gain of such an approach, the improvement of tumor control, and reduction of the dose to organs-at-risk at the same time was analyzed using the QUANTEC biological model.

Methods: Twenty-one prostate cancer patients (70 years average) without previous local therapy received Ga-PSMA-PET/CT imaging. Organs-at-risk and standard prostate target volumes were manually defined on the obtained datasets. A PET active volume (PTV_PET) was segmented with a 40% of the maximum activity uptake in the lesion as threshold followed by manual adaption. Five different treatment plan variations were calculated for each patient. Analysis of derived treatment plans was done according to QUANTEC with in-house developed software. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was calculated for all plan variations.

Results: Comparing the conventional plans to the plans with integrated boost and plans just treating the PET-positive tumor volume, we found that TCP increased to (95.2 ± 0.5%) for an integrated boost with 75.6 Gy, (98.1 ± 0.3%) for an integrated boost with 80 Gy, (94.7 ± 0.8%) for treatment of PET-positive volume with 75 Gy, and to (99.4 ± 0.1%) for treating PET-positive volume with 95 Gy (all p < 0.0001). For the integrated boost with 80 Gy, a significant increase of the median NTCP of the rectum was found, for all other plans no statistical significant increase in the NTCP neither of the rectum nor the bladder was found.

Conclusions: Our study demonstrates that the use of Ga-PSMA-PET/CT image information allows for more individualized prostate treatment planning. TCP values of identified active tumor volumes were increased, while rectum and bladder NTCP values either remained the same or were even lower. However, further studies need to clarify the clinical benefit for the patients applying these techniques.
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http://dx.doi.org/10.1007/s00259-018-3954-yDOI Listing
July 2018

Predictors of overall survival in metastatic castration-resistant prostate cancer patients receiving [Lu]Lu-PSMA-617 radioligand therapy.

Oncotarget 2017 Nov 7;8(61):103108-103116. Epub 2017 Oct 7.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis of and therapy for metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to measure overall-survival (OS) in mCRPC patients who received either abiraterone or enzalutamide prior to PSMA therapy. The second aim of this study was to analyse the predictors of OS according to different pre-therapeutic parameters and also the responses to the first cycle of radioligand therapy (RLT) base on PSA level. Patients with mCRPC and a history of therapy with either abiraterone or enzalutamide or both, were included in this study. Different laboratory tests and pre-therapeutic parameters have been included into the analysis. One-hundred patients received a total of 347 cycles of Lu-PSMA (median: three cycles). 69 patients showed a decline in PSA two months after the first cycle, and 38 of those patients showed a PSA decline of = > 50%. The median OS was 60 weeks. In the multivariate analysis, the level of albumin, AST and haemoglobin, existence of liver metastases and a decline of > 14% in PSA level had a significant impact on overall-survival. The median OS is significantly longer in patients without hepatic involvement, with high levels of albumin and Hb and low levels of AST. A decline in PSA levels of more than 14% was the most important response parameter with regard to overall survival.
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http://dx.doi.org/10.18632/oncotarget.21600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732715PMC
November 2017

Cardiovascular magnetic resonance imaging and clinical performance of somatostatin receptor positron emission tomography in cardiac sarcoidosis.

ESC Heart Fail 2018 04 12;5(2):249-261. Epub 2017 Dec 12.

Department of Internal Medicine II, Cardiology, Pneumology and Angiology, University Hospital Bonn, Bonn, Germany.

Aims: Cardiac affection constitutes a major limiting condition in systemic sarcoidosis. The primary objective of this study was to investigate the persistence rate of cardiac sarcoid involvement by cardiovascular magnetic resonance (CMR) imaging in patients diagnosed with cardiac sarcoidosis (CS). Moreover, we examined the additional insights into myocardial damage's characteristics gained by somatostatin receptor scintigraphy.

Methods And Results: In a pilot study, we had previously identified cardiac involvement-diagnosed by CMR imaging-to be present in 29 of 188 patients (15.4%) with histologically proven, extra-CS. Out of these initial 29 CS-positive patients, 27 patients (49.9 ± 11.8 years, 59.3% male) were presently re-examined and underwent a second CMR study and complementary standard clinical testing. Somatostatin receptor scintigraphy using the ligand Ga-DOTATOC was additionally performed when clinically indicated (17 patients). Within a median follow-up period of 2.6 years, none of the initial 29 patients deceased or experienced aborted sudden cardiac death. However, two patients developed third-degree atrioventricular block that required device therapy. Among the 27 re-examined CS patients, pathological CMR findings persisted in 14 of 27 patients (51.9%). CS remission was primarily due to a resolution of acute inflammatory processes. Ga-DOTATOC positron emission tomography/computed tomography (PET/CT) identified one patient with regions of raised tracer uptake that concorded with acute inflammatory changes, as assessed by CMR; this patient received no immunosuppressive medication at the time of PET/CT execution.

Conclusions: Within follow-up, CS persisted in barely half the patients, and the patients were not afflicted with cardiac death. Additional Ga-DOTATOC PET/CT allowed for visualization of acute myocardial inflammation.
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http://dx.doi.org/10.1002/ehf2.12243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880659PMC
April 2018

Radioligand therapy of metastatic prostate cancer using Lu-PSMA-617 after radiation exposure to Ra-dichloride.

Oncotarget 2017 Aug 25;8(33):55567-55574. Epub 2017 Feb 25.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

Radioligand therapy with Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of Lu-PSMA-617 after exposure to more cycles of Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with Ra. Group 1 included 20 patients, who had received therapy with Ra prior to Lu-PSMA-617 therapy. Group 2, which was the control group regarding hematotoxicity, comprised 29 patients without any history of a bone-targeted radionuclide therapy. No CTC 4° hematotoxicity was observed in the entire study population. There was no CTC 3° or CTC 4° leucopenia in either group. One and three patients from group 1 and 2, respectively, showed CTC 3° anemia. In group 1 there was significantly more CTC 2° anemia (50% vs. 6.9%) (p=0.008). One patient from group 1 (5%) showed a CTC 3° thrombocytopenia without any concurrent anemia, and two patients from group 2 (7%) showed a CTC 3° thrombocytopenia, one with CTC 3° anemia and one without any anemia. There were no significant differences between the two groups regarding leucopenia and thrombocytopenia. These results confirmed that performing repeated cycles of Lu-PSMA-617 after Ra seems to be safe with a very small probability of hematotoxicity.
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http://dx.doi.org/10.18632/oncotarget.15698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589682PMC
August 2017

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer.

Oncotarget 2017 Aug 6;8(33):55094-55103. Epub 2017 Jul 6.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

Radioligand therapy (RLT) with Lu-177-labeled PSMA-ligands is a new therapy option for prostate cancer. Biodistribution in normal tissues is of interest for therapy planning. We evaluated if the biodistribution of Ga-68-PSMA-11 is influenced by tumor load.

Results: In patients with high tumor load, SUV was reduced to 61.5% in the lacrimal glands, to 56.6% in the parotid glands, to 63.7% in the submandibular glands, to 61.3% in the sublingual glands and to 55.4% in the kidneys ( < 0.001). Further significant differences were observed for brain, mediastinum, liver, spleen and muscle. Total tracer retention was higher in patients with high tumor load ( < 0.05). SUV in lacrimal, salivary glands and kidneys correlated negatively with PSA.

Materials And Methods: 135 patients were retrospectively evaluated. SUV was measured in the lacrimal and salivary glands, brain, heart, liver, spleen, kidneys, muscle and bone. SUV was correlated with visual tumor load, total tracer retention and PSA.

Conclusions: Patients with high tumor load show a significant reduction of tracer uptake in dose-limiting organs. As similar effects might occur when performing RLT using Lu-177-labeled PSMA-ligands, individual adaptations of therapy protocols based on diagnostic PSMA PET imaging before therapy might help to further increase efficacy and safety of RLT.
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http://dx.doi.org/10.18632/oncotarget.19049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589644PMC
August 2017

F-fluoroethyl-L-tyrosine positron emission tomography-guided diagnosis of a malignant intramedullary spinal cord tumor.

Oncol Lett 2016 Dec 10;12(6):4705-4707. Epub 2016 Oct 10.

Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, 53127 Bonn, Germany; Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, 53127 Bonn, Germany; Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, 53129 Bonn, Germany.

Diagnosis in patients with a suspected malignant intramedullary lesion that requires biopsy for definitive diagnosis may be challenging, as spinal cord surgery carries the risk of irreversible neurological deficits. The current study presents the first case of F-fluoroethyl-L-tyrosine (F-FET) positron emission tomography (PET) imaging in a patient with a spinal cord tumor. The patient was unsuitable for magnetic resonance imaging due to his implanted cardiac defibrillator. F-FET PET indicated a high-grade malignancy of the spinal cord, justifying tumor biopsy. Histological analysis was compatible with a malignant melanoma. This is also the first report demonstrating the FET-PET appearance/metabolic phenotype of a malignant melanoma of the spinal cord.
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http://dx.doi.org/10.3892/ol.2016.5234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228534PMC
December 2016

Matching the reaction-diffusion simulation to dynamic [F]FMISO PET measurements in tumors: extension to a flow-limited oxygen-dependent model.

Physiol Meas 2017 02 5;38(2):188-204. Epub 2017 Jan 5.

Department of Nuclear Medicine, Technische Universität München, Klinikum rechts der Isar, Germany.

Positron-emission tomography (PET) with hypoxia specific tracers provides a noninvasive method to assess the tumor oxygenation status. Reaction-diffusion models have advantages in revealing the quantitative relation between in vivo imaging and the tumor microenvironment. However, there is no quantitative comparison of the simulation results with the real PET measurements yet. The lack of experimental support hampers further applications of computational simulation models. This study aims to compare the simulation results with a preclinical [F]FMISO PET study and to optimize the reaction-diffusion model accordingly. Nude mice with xenografted human squamous cell carcinomas (CAL33) were investigated with a 2 h dynamic [F]FMISO PET followed by immunofluorescence staining using the hypoxia marker pimonidazole and the endothelium marker CD 31. A large data pool of tumor time-activity curves (TAC) was simulated for each mouse by feeding the arterial input function (AIF) extracted from experiments into the model with different configurations of the tumor microenvironment. A measured TAC was considered to match a simulated TAC when the difference metric was below a certain, noise-dependent threshold. As an extension to the well-established Kelly model, a flow-limited oxygen-dependent (FLOD) model was developed to improve the matching between measurements and simulations. The matching rate between the simulated TACs of the Kelly model and the mouse PET data ranged from 0 to 28.1% (on average 9.8%). By modifying the Kelly model to an FLOD model, the matching rate between the simulation and the PET measurements could be improved to 41.2-84.8% (on average 64.4%). Using a simulation data pool and a matching strategy, we were able to compare the simulated temporal course of dynamic PET with in vivo measurements. By modifying the Kelly model to a FLOD model, the computational simulation was able to approach the dynamic [F]FMISO measurements in the investigated tumors.
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http://dx.doi.org/10.1088/1361-6579/aa5071DOI Listing
February 2017

Unsupervised consensus cluster analysis of [18F]-fluoroethyl-L-tyrosine positron emission tomography identified textural features for the diagnosis of pseudoprogression in high-grade glioma.

Oncotarget 2017 Jan;8(5):8294-8304

Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Germany.

Rationale: Timely detection of pseudoprogression (PSP) is crucial for the management of patients with high-grade glioma (HGG) but remains difficult. Textural features of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) mirror tumor uptake heterogeneity; some of them may be associated with tumor progression.

Methods: Fourteen patients with HGG and suspected of PSP underwent FET-PET imaging. A set of 19 conventional and textural FET-PET features were evaluated and subjected to unsupervised consensus clustering. The final diagnosis of true progression vs. PSP was based on follow-up MRI using RANO criteria.

Results: Three robust clusters have been identified based on 10 predominantly textural FET-PET features. None of the patients with PSP fell into cluster 2, which was associated with high values for textural FET-PET markers of uptake heterogeneity. Three out of 4 patients with PSP were assigned to cluster 3 that was largely associated with low values of textural FET-PET features. By comparison, tumor-to-normal brain ratio (TNRmax) at the optimal cutoff 2.1 was less predictive of PSP (negative predictive value 57% for detecting true progression, p=0.07 vs. 75% with cluster 3, p=0.04).

Principal Conclusions: Clustering based on textural O-(2-[18F]fluoroethyl)-L-tyrosine PET features may provide valuable information in assessing the elusive phenomenon of pseudoprogression.
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http://dx.doi.org/10.18632/oncotarget.14166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352401PMC
January 2017

Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with Ra: Proof of Concept.

J Nucl Med 2017 03 22;58(3):438-444. Epub 2016 Sep 22.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

We retrospectively evaluated the utility of Ga-PSMA-11 PET for planning RaCl therapy of patients with metastatic prostate cancer and its impact on the therapeutic response as determined by prostate-specific antigen (PSA) and alkaline phosphatase (ALP), as well as the correlation of PSA changes with the results of prostate-specific membrane antigen (PSMA) PET follow-up scans. Sixty-three patients with a median age of 73 y who underwent 307 cycles of therapy with RaCl were analyzed. In 31 patients, bone scanning and radiologic imaging were performed for pretherapeutic imaging (group 1). In 32 patients, bone scanning and PSMA PET were performed before therapy (group 2). Patients with small lymph node metastases and local recurrence were not excluded from treatment, consistent with current guidelines. PSA and ALP were measured before each treatment cycle and 4 wk after the final cycle. Thirteen patients from group 2, who underwent a second PSMA PET scan as a follow-up, were evaluated to determine the significance of PSA changes as a follow-up marker. In group 1, 4 patients (12.9%) showed a PSA decline, of whom 2 patients and 1 patient showed a PSA decline of more than 30% and more than 50%, respectively. In contrast, in group 2, 14 patients (43.8%) showed a PSA decline, of whom 10 and 8 patients showed a decline of more than 30% and more than 50%, respectively ( = 0.007). Thirty-seven patients had a high ALP level (19 from group 1 and 18 from group 2). Twelve (63.2%) and 16 (88.9%) patients in groups 1 and 2, respectively, showed an ALP decline. This difference was not significant; however, 7 (36%) and 13 (72.2%) patients in groups 1 and 2, respectively, showed an ALP decline of more than 30% ( = 0.04). Considering any ALP decline as a response, no patient with increasing ALP showed a PSA response ( = 0.036). There was a significant correlation between the PSA changes and the therapeutic response according to follow-up PSMA PET. When PSMA PET is used as the gatekeeper in addition to bone scanning, radionuclide therapy with Ra may be more effective and have more success regarding changes in the PSA. An increase in PSA during therapy cycles occurs because of disease progression.
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http://dx.doi.org/10.2967/jnumed.116.178533DOI Listing
March 2017

Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with 177Lu-PSMA-617.

J Nucl Med 2017 02 1;58(2):312-319. Epub 2016 Sep 1.

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany

Radioligand therapy (RLT) with Lu-PSMA-617 (PSMA is prostate-specific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. In this study, we evaluated the effect of different pretherapeutic parameters on the therapeutic response measured by prostate-specific antigen (PSA) 2 mo after RLT.

Methods: RLT was performed in 40 hormone-refractory patients with distant metastases and progressive disease (mean age, 71.4 y). Ga-PSMA-11 PET/CT was performed in all patients 1-2 wk before RLT. All patients were treated with a mean of 6 GBq. The SUV of tumor lesions was determined using region-of-interest analysis. Complete blood counts, renal and liver function assessments, previous therapies, pain medication, and SUVs were included in the analysis. PSA was assessed 2 mo after RLT.

Results: In the univariate analysis, younger age, higher levels of γ-glutamyl transferase, lower pretherapeutic hemoglobin, a higher Gleason score, a higher number of platelets, higher C-reactive protein, regular need for pain medication, and higher lactate dehydrogenase had a negative impact on the therapeutic response; however, the multivariate analysis revealed that the most significant independent factors were the number of platelets and regular need for pain medication. The response was independent of the amount of PSMA uptake as well as previous therapies and other measured factors.

Conclusion: A PSA decline of more than 50% was observed significantly more in patients without a regular need for analgesics.
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http://dx.doi.org/10.2967/jnumed.116.178228DOI Listing
February 2017

Facial movement disorder and dopamine imaging in a patient with amphetamine abuse.

Parkinsonism Relat Disord 2016 10 2;31:153-155. Epub 2016 Aug 2.

Department of Neurology, University of Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2016.07.020DOI Listing
October 2016

Quantitative Analysis of [F]FMISO PET for Tumor Hypoxia: Correlation of Modeling Results with Immunohistochemistry.

Mol Imaging Biol 2017 02;19(1):120-129

Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse. 22, 81675, Munich, Germany.

Purpose: Quantitative evaluation of tumor hypoxia based on H-1-(3-[F]fluoro-2-hydroxypropyl)-2-nitroimidazole ([F]FMISO) positron emission tomography (PET) can deliver important information for treatment planning in radiotherapy. However, the merits and limitations of different analysis methods in revealing the underlying physiological feature are not clear. This study aimed to assess these quantitative analysis methods with the support of immunohistological data.

Procedures: Sixteen nude mice bearing xenografted human squamous cell carcinomas (FaDu or CAL-33) were scanned using 2-h dynamic [F]FMISO PET. Tumors were resected and sliced, and the hypoxia marker pimonidazole was immunostained followed by H&E staining. The pimonidazole signal was segmented using a k-means clustering algorithm, and the hypoxic fraction (HF) was calculated as the hypoxic area/viable tumor-tissue-area ratio pooled over three tissue slices from the apical, center, and basal layers. PET images were analyzed using various methods including static analysis [standard uptake value (SUV), tumor-to-blood ratio (T/B), tumor-to-muscle ratio (T/M)] and kinetic modeling (Casciari αk , irreversible and reversible two-tissue compartment k , Thorwarth w k , Patlak K , Logan V , Cho K), and correlated with HF.

Results: No significant correlation was found for static analysis. A significant correlation between k of the irreversible two-tissue compartment model and HF was observed (r = 0.61, p = 0.01). The correlation between HF and αk of the Casciari model could be improved through reducing local minima by testing more sets of initial values (r = 0.59, p = 0.02) or by reducing the model complexity by fixing three parameters (r = 0.63, p = 0.0008).

Conclusions: With support of immunohistochemistry data, this study shows that various analysis methods for [F]FMISO PET perform differently for assessment of tumor hypoxia. A better fitting quality does not necessarily mean a higher physiological correlation. Hypoxia PET analysis needs to consider both the mathematical stability and physiological fidelity. Based on the results of this study, preference should be given to the irreversible two-tissue compartment model as well as the Casciari model with reduced parameters.
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http://dx.doi.org/10.1007/s11307-016-0975-4DOI Listing
February 2017

F-fluoroethyl-L-tyrosine positron emission tomography for the differential diagnosis of tumefactive multiple sclerosis versus glioma: A case report.

Oncol Lett 2016 Mar 4;11(3):2195-2198. Epub 2016 Feb 4.

Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Bonn 53127, Germany.

Large demyelinating inflammatory central nervous system (CNS) lesions may present with contrast enhancement on magnetic resonance imaging and may mimic CNS tumors such as glioma. In ambiguous cases, new diagnostic tools that may be helpful for distinguishing between demyelinating inflammatory and neoplastic CNS lesions are required. The current study presents the case of a patient with a large contrast-enhanced frontal brain lesion, who was initially diagnosed with tumefactive multiple sclerosis. Following the progression of the brain lesion, an F-fluoroethyl-L-tyrosine positron emission tomography (F-FET PET) was performed, revealing markedly elevated static F-FET uptake parameters along with time activity-curves consistent with glioma. Subsequently, a biopsy was undertaken, which confirmed the presence of anaplastic oligoastrocytoma. This case illustrates that F-FET PET may provide useful diagnostic information in cases where distinction between neoplastic and demyelinating inflammatory CNS lesions is challenging. However, further systematic and prospective analyses are warranted to explore the value of this method in this setting.
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http://dx.doi.org/10.3892/ol.2016.4189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774557PMC
March 2016

FDG PET performed at thyroid remnant ablation has a higher predictive value for long-term survival of high-risk patients with well-differentiated thyroid cancer than radioiodine uptake.

Clin Nucl Med 2015 May;40(5):378-83

From the *Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan; †Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University Munich, Munich; ‡Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany; and §Department of Biostatistics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Purpose: The predictive value of FDG PET at thyroid remnant ablation was evaluated in comparison to radioiodine uptake in high-risk patients with differentiated thyroid cancer.

Patients And Methods: One hundred forty-one patients who underwent radioiodine therapy (RIT) after total thyroidectomy and received at least 1 further RIT due to suspected metastases were retrospectively analyzed. Patients had not received RIT previously. FDG PET was performed before thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg between the first and second RIT, ΔTg).

Results: Biochemical response could be evaluated in 80 patients; survival data could be obtained for 88 patients (maximum, 124 months). Biochemical response was significantly better in patients with radioiodine-positive metastases compared with patients with radioiodine-negative metastases (median ΔTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding survival, deaths occurred later in patients with radioiodine-positive metastases compared with radioiodine-negative patients; however, there was no significant difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05). Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer biochemical response compared with patients with FDG-negative metastases (median ΔTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P < 0.05).

Conclusions: At thyroid remnant ablation, FDG PET is more predictive for long-term survival, whereas radioiodine uptake is more important for short-term response. FDG PET performed at thyroid remnant ablation might represent a useful tool for management of high-risk patients with differentiated thyroid cancer.
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http://dx.doi.org/10.1097/RLU.0000000000000699DOI Listing
May 2015

α-Radioimmunotherapy with ²¹³Bi-anti-CD38 immunoconjugates is effective in a mouse model of human multiple myeloma.

Oncotarget 2015 Mar;6(7):4692-703

Department of Nuclear Medicine, Technische Universität München, Munich, Germany.

In spite of development of molecular therapeutics, multiple myeloma (MM) is fatal in most cases. CD38 is a promising target for selective treatment of MM. We tested radioimmunoconjugates consisting of the α-emitter ²¹³Bi coupled to an anti-CD38 MAb in preclinical treatment of MM. Efficacy of ²¹³Bi-anti-CD38-MAb was assayed towards different MM cell lines with regard to induction of DNA double-strand breaks, induction of apoptosis and initiation of cell cycle arrest. Moreover, mice bearing luciferase-expressing MM xenografts were treated with ²¹³Bi-anti-CD38-MAb. Therapeutic efficacy was monitored by bioluminescence imaging, overall survival and histology. ²¹³Bi-anti-CD38-MAb treatment induced DNA damage which did not result in activation of the G2 DNA-damage-response checkpoint, but instead in mitotic arrest and subsequent mitotic catastrophe. The anti-tumor effect of ²¹³Bi-anti-CD38-MAb correlated with the expression level of CD38 in each MM cell line. In myeloma xenografts, treatment with ²¹³Bi-anti-CD38-MAb suppressed tumor growth via induction of apoptosis in tumor tissue and significantly prolonged survival compared to controls. The major organ systems did not show any signs of ²¹³Bi-induced toxicity. Preclinical treatment of MM with ²¹³Bi-anti-CD38-MAb turned out as an effective therapeutic option.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467108PMC
http://dx.doi.org/10.18632/oncotarget.2986DOI Listing
March 2015

Diffuse renal (18)F-FDG uptake of a patient with fever of unknown origin revealed sarcoidosis.

Clin Nucl Med 2014 Jul;39(7):648-9

From the Departments of *Nuclear Medicine, and †Internal Medicine II, Hokkaido University Graduate School of Medicine; and ‡Department of Pathology, KKR Sapporo Medical Center, Sapporo, Hokkaido, Japan.

We report about the usefulness of F-FDG PET for the detection and therapy response evaluation of renal sarcoidosis. A 55-year-old woman presented with a condition diagnosed with pulmonary and ocular sarcoidosis 2 years before having anemia and acute deterioration of renal function. FDG PET revealed diffuse increased FDG uptake in both kidneys and the spleen. Histopathologic examination of a renal biopsy sample revealed granulomatous interstitial nephritis with sarcoidosis. After methylprednisolone treatment, the abnormal FDG uptake resolved completely with improvement of symptoms. FDG PET is a useful tool to detect active sarcoidosis regions and to monitor treatment efficacy.
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http://dx.doi.org/10.1097/RLU.0000000000000488DOI Listing
July 2014
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