Publications by authors named "Florent Cachin"

41 Publications

Decision Tree With Only Two Musculoskeletal Sites to Diagnose Polymyalgia Rheumatica Using [F]FDG PET-CT.

Front Med (Lausanne) 2021 17;8:646974. Epub 2021 Feb 17.

Department of Nuclear Medicine, Jean Perrin Oncology Institute of Clermont-Ferrand, Clermont-Ferrand, France.

The aim of this study was to find the best ordered combination of two FDG positive musculoskeletal sites with a machine learning algorithm to diagnose polymyalgia rheumatica (PMR) vs. other rheumatisms in a cohort of patients with inflammatory rheumatisms. This retrospective study included 140 patients who underwent [F]FDG PET-CT and whose final diagnosis was inflammatory rheumatism. The cohort was randomized, stratified on the final diagnosis into a training and a validation cohort. FDG uptake of 17 musculoskeletal sites was evaluated visually and set positive if uptake was at least equal to that of the liver. A decision tree classifier was trained and validated to find the best combination of two positives sites to diagnose PMR. Diagnosis performances were measured first, for each musculoskeletal site, secondly for combination of two positive sites and thirdly using the decision tree created with machine learning. 55 patients with PMR and 85 patients with other inflammatory rheumatisms were included. Musculoskeletal sites, used either individually or in combination of two, were highly imbalanced to diagnose PMR with a high specificity and a low sensitivity. The machine learning algorithm identified an optimal ordered combination of two sites to diagnose PMR. This required a positive interspinous bursa or, if negative, a positive trochanteric bursa. Following the decision tree, sensitivity and specificity to diagnose PMR were respectively 73.2 and 87.5% in the training cohort and 78.6 and 80.1% in the validation cohort. Ordered combination of two visually positive sites leads to PMR diagnosis with an accurate sensitivity and specificity vs. other rheumatisms in a large cohort of patients with inflammatory rheumatisms.
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http://dx.doi.org/10.3389/fmed.2021.646974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928279PMC
February 2021

Benzamide derivative radiotracers targeting melanin for melanoma imaging and therapy: Preclinical/clinical development and combination with other treatments.

Pharmacol Ther 2021 Mar 1;224:107829. Epub 2021 Mar 1.

Université Clermont Auvergne, INSERM, Imagerie Moléculaire et Stratégies Théranostiques, UMR1240, 58 Rue Montalembert, 63005 Clermont-Ferrand, Cedex, France. Electronic address:

Cutaneous melanoma arises from proliferating melanocytes, cells specialized in the production of melanin. This property means melanin can be considered as a target for monitoring melanoma patients using nuclear imaging or targeted radionuclide therapy (TRT). Since the 1970s, many researchers have shown that specific molecules can interfere with melanin. This paper reviews some such molecules: benzamide structures improved to increase their pharmacokinetics for imaging or TRT. We first describe the characteristics and biosynthesis of melanin, and the main features of melanin tracers. The second part summarizes the preclinical and corresponding clinical studies on imaging. The last section presents TRT results from ongoing protocols and discusses combinations with other therapies as an opportunity for melanoma non-responders or patients resistant to treatments.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107829DOI Listing
March 2021

Internal dosimetry of [ Tc]NTP15-5 radiotracer for cartilage imaging in preclinical and clinical models using the GATE Monte Carlo platform.

Med Phys 2021 Jan 7;48(1):477-487. Epub 2020 Dec 7.

Université Clermont Auvergne, CNRS/IN2P3, Laboratoire de Physique de Clermont, UMR6533, 4 avenue Blaise Pascal TSA 60026 CS, Clermont-Ferrand, Aubière cedex, 60026 63178, France.

Purpose: This study aims to perform dosimetry for [ Tc]NTP15-5 radiotracer used in imaging of articular cartilage in rabbits and humans. The radiotracer (covered by a world patent WO 01/00621 A1) has been proposed in the previous years for the study of cartilage in osteoarthritis diseases. A sensitive imaging approach is essential to quantify osteoarthritis progression and monitor response to new therapies. [ Tc]NTP15-5 binds to cartilage proteoglycans whose decreased content is associated to a loss of biomedical function of cartilage. We have implemented the whole dosimetry study concerning this new radiotracer for rabbits and humans using the GATE Monte Carlo platform.

Materials And Methods: Absorbed doses to critical organs are determined using the MIRD formalism. Biodistribution data are obtained by organ sampling, measuring the activity in organs for three rabbits sacrificed at various times postadministration, and by SPECT/CT imaging at different times after injection. Most important sources are cartilages (in knees and intervertebral discs), due to localization together with the liver and kidneys due to excretion of the agent. S-values are calculated from rabbit's CT scan and human CT scan using the GATE v8.0 Monte Carlo platform. Cumulated activity in humans is extrapolated from animals using the %kg-dose/g method. Particular attention is given to dose calculation in bones, bone marrow and organs at risk.

Results: The dosimetry performed in rabbits shows highest absorbed doses for liver and kidneys with respectively 22.5 and 43.8 µGy per MBq of injected activity. In humans, we found absorbed doses for a maximum injected activity of 15 MBq/kg, that is, 1050 MBq for an adult of 70 kgs of 9.03 mGy for kidneys and 4.16 mGy for knee cartilages. Effective dose is 2.69 µSv/MBq.

Conclusions: The dosimetry profile of [ Tc]NTP15-5 in the context of preclinical trials is of major importance in order to make sure that organs at risk are not overexposed. GATE provides all the capability needed to calculate dose profiles for internal dosimetry. The extrapolation of the dose for a human model is a first step towards clinical trials.
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http://dx.doi.org/10.1002/mp.14603DOI Listing
January 2021

Comparison of 18FDG-PET/CT and conventional follow-up methods in colorectal cancer: A randomised prospective study.

Dig Liver Dis 2021 Feb 2;53(2):231-237. Epub 2020 Nov 2.

Department of Medical Oncology, University Hospital, Limoges, France.

Background: A surveillance program was performed in colorectal cancer (CRC) patients after surgery, to diagnose asymptomatic recurrence.

Aims: To assess whether 18-FDG positron emission tomography/CT (PET/CT) improved the detection of recurrence during a 3-year follow-up.

Methods: A multicentre, two-arm randomised prospective trial comparing different 36-month follow-up strategies. Complete colonoscopy was performed at baseline and after 3 years and clinical exams with imaging every 3 months. The conventional arm (A) received carcinoembryonic antigen, liver echography, and alternated between lung radiography and computed tomography (CT) scans. The experimental arm (B) received PET/CT.

Results: A total of 365 patients with colon (79.4%) or rectal cancer (20.6%), stages II (48.2%) or III (50.8%), were enroled in this study. At 36 months, intention-to-treat analysis revealed recurrence in 31 (17.2%) patients in arm A and 47 (25.4%) in arm B (p = 0.063). At 3 years, 7 of 31 relapses (22.5%) in arm A were surgically treated with curative intent, compared to 17 of 47 (36.2%) in arm B (p = 0.25). The rates of recurrence and new cancers were higher in arm B than arm A (p = 0.038).

Conclusions: PET/CT follow-up every 6 months did not increase the rate of recurrence at 3 years or the rate of surgically treated recurrence compared with conventional follow-up.
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http://dx.doi.org/10.1016/j.dld.2020.10.012DOI Listing
February 2021

Utility of F-Fluorodeoxyglucose Positron Emission Tomography in Inflammatory Rheumatism, Particularly Polymyalgia Rheumatica: A Retrospective Study of 222 PET/CT.

Front Med (Lausanne) 2020 13;7:394. Epub 2020 Aug 13.

Jean Perrin Oncology Institute, Department of Nuclear Medicine, Clermont-Ferrand, France.

The objective of this study was to evaluate periarticular FDG uptake scores from F-FDG-PET/CT to identify polymyalgia rheumatica (PMR) within a population presenting rheumatic diseases. A French retrospective study from 2011 to 2015 was conducted. Patients who underwent F-FDG-PET/CT for diagnosis or follow-up of a rheumatism or an unexplained biological inflammatory syndrome were included. Clinical data and final diagnosis were reviewed. Seventeen periarticular sites were sorted by a visual reading enabling us to calculate two scores: mean FDG visual uptake score, number of sites with significant uptake same as that or higher than liver uptake intensity and by a semi-quantitative analysis using mean maximum standardized uptake value (SUVmax). Optimal cutoffs of visual score and SUVmax to diagnose PMR were determined using receiver operating characteristics curves. Among 222 F-FDG PET/CT selected for 215 patients, 161 F-FDG PET/CT were performed in patients who presented inflammatory rheumatism as a final diagnosis (of whom 57 PMR). The presence of at least three sites with significant uptake identified PMR with a sensitivity of 86% and a specificity of 85.5% (AUC 0.872, 95% CI [0.81-0.93]). The mean FDG visual score cutoff to diagnose a PMR was 0.765 with a sensitivity of 82.5% and a specificity of 75.8% (AUC 0.854; 95% CI [0.80-0.91]). The mean SUVmax cutoff to diagnose PMR was 2.168 with a sensitivity of 77.2% and a specificity of 77.6% (AUC 0.842; 95% CI [0.79-0.89]). This study suggests that F-FDG PET/CT had good performances to identify PMR within a population presenting rheumatic diseases.
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http://dx.doi.org/10.3389/fmed.2020.00394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456960PMC
August 2020

[F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer.

EJNMMI Res 2020 Jan 6;10(1). Epub 2020 Jan 6.

Service de Médecine Nucléaire, Centre Jean Perrin, Clermont-Ferrand, France.

Purpose: Pathological complete response to the neoadjuvant therapy (NAT) for triple negative breast cancer (TNBC) is predictive of prolonged patient survival. Methods for early evaluation of NAT efficiency are still needed, in order to rapidly adjust the therapeutic strategy in case of initial non-response. One option for this is molecular imaging of apoptosis induced by chemotherapy. Therefore, we investigated the capacity of [F]ML-10 PET imaging, an apoptosis radiotracer, to detect tumor cell apoptosis and early predict the therapeutic response of human TNBC.

Results: Initially, the induction of apoptosis by different therapies was quantified. We confirmed, in vitro, that paclitaxel or epirubicin, the fundamental cytotoxic drugs for breast cancer, induce apoptosis in TNBC cell lines. Exposure of TNBC models MDA-MB-231 and MDA-MB-468 to these drugs induced a significant increase (p < 0.01) of the apoptotic hallmarks: DNA fragmentation, membrane phospholipid scrambling, and PARP activation. Secondarily, apoptotic fraction was compared to the intracellular accumulation of the radiotracer. [F]ML-10 accumulated in the apoptotic cells after 72 h of treatment by paclitaxel in vitro; this accumulation positively correlated with the apoptotic fraction. In vivo, [F]ML-10 was rapidly cleared from the nontarget organs and mainly eliminated by the kidneys. Comparison of the in vivo [F]FDG, [F]FMISO, and [F]ML-10 uptakes revealed that the tumor accumulation of [F]ML-10 was directly related to the tumor hypoxia level. Finally, after the in vivo treatment of TNBC murine xenografts by paclitaxel, apoptosis was well induced, as demonstrated by the cleaved caspase-3 levels; however, no significant increase of [F]ML-10 accumulation in the tumors was observed, either on day 3 or day 6 after the end of the treatment.

Conclusions: These results highlighted that PET imaging using [F]ML-10 allows the visualization of apoptotic cells in TNBC models. Nevertheless, the increase of the chemotherapy-induced apoptotic response when using paclitaxel could not be assessed using this radiotracer in our mouse model.
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http://dx.doi.org/10.1186/s13550-019-0587-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944726PMC
January 2020

Dual time point [F]FLT-PET for differentiating proliferating tissues vs non-proliferating tissues.

EJNMMI Res 2019 Dec 12;9(1):109. Epub 2019 Dec 12.

Nuclear Medicine Department and Inserm UMR_S 1066 MINT, University of Angers, Angers, France.

Purpose: For differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([F]FDG) dual time point PET could be helpful. Albeit [F]FLT is more specific for tumors than [F]FDG; we explored the role of dual time point [F]FLT-PET for discriminating benign from malignant tissues.

Methods: Before any treatment, 85 womens with de novo unifocal breast cancer underwent three PET acquisitions at 33.94 ± 8.01 min (PET30), 61.45 ± 8.30 min (PET60), and 81.06 ± 12.12 min (PET80) after [F]FLT injection. Semiquantitative analyses of [F]FLT uptake (SUV) were carried out on tumors, liver, bone marrow (4th thoracic vertebra (T4) and humeral head), descending thoracic aorta, muscle (deltoid), and contralateral normal breast. Repeated measures ANOVA tests and Tukey's posttests were used to compare SUVmax of each site at the three time points.

Results: There was a significant increase in SUVmax over time for breast lesions (5.58 ± 3.80; 5.97 ± 4.56; 6.19 ± 4.42; p < 0.0001) (m ± SD for PET30, PET60, and PET80, respectively), and bone marrow (for T4, 8.21 ± 3.17, 9.64 ± 3.66, 10.85 ± 3.63, p < 0.0001; for humeral head, 3.36 ± 1.79, 3.87 ± 1.89, 4.39 ± 2.00, p < 0.0001). A significant decrease in SUVmax over time was observed for liver (6.79 ± 2.03; 6.24 ± 1.99; 5.57 ± 1.74; p < 0.0001), muscle (0.95 ± 0.28; 0.93 ± 0.29; 0.86 ± 0.20; p < 0.027), and aorta (1.18 ± 0.34; 1.01 ± 0.32; 0.97 ± 0.30; p < 0.0001). No significant difference was observed for SUVmax in contralateral breast (0.8364 ± 0.40; 0.78 ± 0.38; 0.80 ± 0.35).

Conclusion: [F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.
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http://dx.doi.org/10.1186/s13550-019-0579-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908533PMC
December 2019

Good clinical practice recommendations for the use of PET/CT in oncology.

Eur J Nucl Med Mol Imaging 2020 01 21;47(1):28-50. Epub 2019 Oct 21.

Nuclear Medicine, Jean Perrin Cancer Institute, Clermont-Ferrand, France.

Positron emission tomography/computed tomography (PET/CT) is a nuclear medicine functional imaging technique with proven clinical value in oncology. PET/CT indications are continually evolving with fresh advances made through research. French practice on the use of PET in oncology was framed in recommendations based on Standards-Options-Recommendations methodology and coordinated by the French federation of Comprehensive Cancer Centres (FNLCC). The recommendations were originally issued in 2002 followed by an update in 2003, but since then, a huge number of scientific papers have been published and new tracers have been licenced for market release. The aim of this work is to bring the 2003 version recommendations up to date. For this purpose, a focus group was set up in collaboration with the French Society for Nuclear Medicine (SFMN) to work on developing good clinical practice recommendations. These good clinical practice recommendations have been awarded joint French National Heath Authority (HAS) and French Cancer Institute (INCa) label status-the stamp of methodological approval. The present document is the outcome of comprehensive literature review and rigorous appraisal by a panel of experts, organ specialists, clinical oncologists, surgeons and imaging specialists. These data were also used for the EANM referral guidelines.
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http://dx.doi.org/10.1007/s00259-019-04553-8DOI Listing
January 2020

Re-treatment With Adjuvant Radioactive Iodine Does Not Improve Recurrence-Free Survival of Patients With Differentiated Thyroid Cancer.

Front Endocrinol (Lausanne) 2019 27;10:671. Epub 2019 Sep 27.

Université Clermont Auvergne, Faculté de Médecine, Clermont-Ferrand, France.

Loco regional persistence or recurrence of differentiated thyroid cancer (DTC) is frequent despite initial thyroidectomy and radioactive iodine therapy (RAI). The aim of this study was to analyze the impact of a complementary adjuvant RAI (Ad-RAI) on disease recurrence following re-operation on patients with locally persistent or recurrent DTC. A retrospective study of 85 patients with DTC was conducted. All patients were initially treated with total thyroidectomy and RAI, and re-operated for a locally persistent or recurrent disease. Propensity score was calculated to predict the impact of Ad-RAI on survival after reoperation, and to reduce the bias of the limited sample size and the prognostic tests. 49 (58%) patients were re-treated with Ad-RAI after re-operation while 36 (42%) were only followed up. Disease recurrence after re-treatment (re-operation ± Ad-RAI) was detected in 31 patients (36.5%). In multivariate analysis, age >55 years (HR: 3.9 [1.6; 9.5]; < 0.00001) was the main poor prognostic factor for recurrence-free survival. Three parameters independently influenced the decision to administer ad-RAI: low number of previous RAI administrations, Nx before re-operation, and pTg > 30 μg/l. These parameters were incorporated in the Propensity score calculation. If ad-RAI tended to improve recurrence-free survival (median survival 17.4 vs. 10.9 months), adjustment using the Propensity score removed any difference between the groups ( = 0.54), confirming the limited value of ad-RAI. In patients with locally persistent or recurrent DTC, age is the main independent prognostic factor. Adjuvant RAI does not improve recurrence-free survival of DTC patients.
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http://dx.doi.org/10.3389/fendo.2019.00671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776597PMC
September 2019

Age, thyroglobulin levels and ATA risk stratification predict 10-year survival rate of differentiated thyroid cancer patients.

PLoS One 2019 19;14(8):e0221298. Epub 2019 Aug 19.

CHU Clermont-Ferrand, Service d'endocrinologie, diabétologie et maladies métaboliques, Clermont-Ferrand, France.

Introduction: Differentiated thyroid cancer (DTC) is the most common of endocrine cancers. Many studies have focused on recurrence-free survival of DTC patients, however, few studies have addressed overall survival rates. Given its very good prognosis, estimating overall or long-term survival in patients with DTC seems rational. So far, neither the impact of pre- and post-ablation thyroglobulin, nor that of initial American Thyroid Association (ATA) risk stratification on long-term disease-specific survival, have been sufficiently studied.

Objective: The aim of this study was to determine the factors that influence long-term disease-specific survival and thyroglobulin levels in patients with DTC who have been previously treated with thyroidectomy and radioactive iodine (RAI) remnant ablation.

Patients And Methods: This observational retrospective study included 1093 patients who were treated for DTC between 1995 and 2010 and are still monitored in our tertiary center. Only patients who needed RAI ablation after thyroidectomy were included in this study. Patients who were treated with RAI following rhTSH stimulation, patients who presented positive anti-thyroglobulin antibodies, and patients who had micro-cancers were excluded. Pre-ablation stimulated thyroglobulin (Pre-ablation sTg) was measured after thyroid hormone withdrawal (THW), just before RAI.

Results: According to ATA standards, 29 patients (2.7%) were classified as high-risk patients. Initial ATA high-recurrence risk rating (HR 21.9; 95% CI: 8.5-56.3), age>55 years (HR 23.8; 95%-CI: 7.5-75.3) and pre-ablation sTg≥30 μg/l (HR 8.4; 95% CI: 4.6-15.3) significantly impacted ten-year survival. Moreover, age over 45 years, ATA moderate-risk and follicular DTC were also significant. Ten-year survival was lower in ATA high-risk patients (51% vs 95% and 93% for the low and intermediate risk; p<10-7), patients older than 55 years (82% vs 98%; p<10-7), and in patients with pre-ablation sTg≥30 (78% vs 95%; p<10-7). Three rates of long-term survival were distinguished: excellent (survival rate of 99% in patients<55 years with pre-ablation sTg <30μg/l) representing 59% of the cohort, moderate (survival rate of 94.5% in patients <55 years with pre-ablation sTg ≥30μg/l or ≥55 years with pre-ablation sTg <30 μg/l) representing 38% of the cohort, and low (survival rate of 49% in patients ≥55 years with pre-ablation sTg ≥30μg/l) representing 3% of the cohort.

Conclusion: Initial ATA high-risk classification, age over 55 years old and pre-ablation sTg ≥30 μg/l are the main negative factors that influence the ten-year survival in DTC. We suggest three categories of overall survival rates. Patients older than 55 years with pre-ablation sTg ≥30 μg/l have the worst survival rate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221298PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699685PMC
April 2020

Homoharringtonine, an approved anti-leukemia drug, suppresses triple negative breast cancer growth through a rapid reduction of anti-apoptotic protein abundance.

Am J Cancer Res 2019 1;9(5):1043-1060. Epub 2019 May 1.

University Clermont Auvergne, INSERM U1240 Centre Jean Perrin, 58 Rue Montalembert, 63011 Clermont-Ferrand, France.

Triple negative breast cancers (TNBC) without gene mutation or BRCAness are nowadays the breast malignancies most difficult to treat. Improvement of their treatment, for all phases of the disease, is an important unmet medical need. We analyzed the effect of homoharringtonine (HHT), a natural protein synthesis inhibitor approved for treatment of chronic myeloid leukemia, on four cell lines representing aggressive, non-mutated, TNBC genomic categories. We show that HHT inhibits in vitro growth of all cell lines for more than 80%, after 48-72 h exposure to 20-100 ng/mL, the concentrations achievable in human plasma after subcutaneous administration of the drug. HHT, at 100 ng/mL, strongly reduced levels of a major TNBC survival factor, anti-apoptotic protein Mcl-1, after only 2 h of exposure, in all cell lines except MDA-MB-231. Other anti-apoptotic proteins, Bcl-2, survivin and XIAP, were also strongly downregulated. Moreover, in vivo growth of the least sensitive cell line to HHT in vitro, MDA-MB-231, was inhibited for 36.5% in mice, by 1 mg/kg of the drug, given subcutaneously, bi-daily, over 7 days. These results demonstrate marked antineoplastic activity of homoharringtonine in TNBC, making further development of the drug in this disease highly warranted.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556597PMC
May 2019

Stimulated Thyroglobulin and Thyroglobulin Reduction Index Predict Excellent Response in Differentiated Thyroid Cancers.

J Clin Endocrinol Metab 2019 08;104(8):3462-3472

CHU Clermont-Ferrand, Service d'Endocrinologie, Diabétologie et Maladies Métaboliques, Clermont-Ferrand, France.

Context: Despite its good prognosis, differentiated thyroid cancer (DTC) is characterized by high rates of disease persistence and recurrence. Estimation of long-term remission (excellent response) thanks to specific parameters could help to individualize the active surveillance schedule.

Objective: Evaluation of the ability of stimulated thyroglobulin (Tg) and Tg reduction index (TRI) to predict long-term remission in patients with DTC managed by thyroidectomy and radioactive iodine (RAI) remnant ablation.

Patients And Interventions: Observational retrospective study of 1093 patients treated for DTC between 1995 and 2010. Preablation stimulated thyroglobulin (presTg) was measured under thyroid hormone withdrawal just before RAI. Recombinant human TSH-stimulated thyroglobulin (sTg) was measured at first evaluation of the initial management 6 to 12 months after RAI. TRI was calculated based on pre-Tg and sTg.

Results: After univariate and multivariate analyses, lymph node invasion (N1, OR = 2.08; 95% CI, 1.19 to 3.64), presTg (OR = 4.04; 95% CI, 2.56 to 6.38), sTg (OR = 2.62; 95% CI, 2.05 to 3.34), and TRI (OR = 0.43; 95% CI, 0.21 to 0.88) were identified as independent prognostic factors influencing the rate of disease persistence or recurrence after the initial management. Receiver operating characteristic analysis identified presTg cutoff (<10 µg/L) to predict excellent response, with a negative predictive value of 94%, and validated for higher stages (T3/T4, N1). Furthermore, sTg <1 µg/L predicts excellent response. TRI >60% for the entire cohort and 62.5% for locally advanced disease (T3/T4, N1) was sensitive predictor for excellent response.

Conclusion: This study identifies presTg, sTg, and TRI as highly sensitive predictors of excellent response in patients with DTC and subsequently disease-free status. The cutoff of such parameters is also adapted for patients with higher tumor stages (T3/T4, N1).
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http://dx.doi.org/10.1210/jc.2018-02680DOI Listing
August 2019

[Update of the recommendations of good clinical practice for the use of PET in oncology].

Bull Cancer 2019 Mar 23;106(3):262-274. Epub 2019 Jan 23.

Jean-Perrin Comprehensive Cancer Center, service de médecin nucléaire, 58, rue Montalembert, 63100 Clermont-Ferrand, France. Electronic address:

Positron Emission Tomography (PET) is a functional nuclear medicine imaging technique which clinical value in oncology has been demonstrated. PET indications are constantly evolving, thanks to the contribution of research. The use of PET in oncology has been the subject of recommendations according to the Standard-Options-Recommendations methodology from the Fédération Nationale des Centres de Lutte Contre le Cancer in 2002, updated in 2003. However, many scientific works have been published since 2003 and new tracers have also obtained a marketing authorization in France. The objective of this work was therefore to update the recommendations established in 2003. In this context, in collaboration with the Société française de médecine nucléaire, a working group was set up for the development of good clinical practice recommendations under the HAS-INCA methodological label. The present document is issued from a comprehensive review of the literature and rigorous appraisal by a panel of national experts, organ specialists, clinical oncologists, surgeons, and imaging specialists. It is intended to be used as a guide to decision-making for those oncology teams that are able to manage patients in various situations in which the AMM label is not sufficiently precise.
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http://dx.doi.org/10.1016/j.bulcan.2019.01.002DOI Listing
March 2019

Assessment of four different cardiac softwares for evaluation of LVEF with CZT-SPECT vs CMR in 48 patients with recent STEMI.

J Nucl Cardiol 2020 12 13;27(6):2017-2026. Epub 2018 Nov 13.

Department of Radiology, CHU Gabriel Montpied, Clermont-Ferrand, France.

Purpose: To compare, vs CMR, four softwares: quantitative gated SPECT (QGS), myometrix (MX), corridor 4DM (4DM), and Emory toolbox (ECTb) to evaluate left ventricular ejection fraction (LVEF), end-systolic (ESV), and end-diastolic volumes (EDVs) by gated MPI CZT-SPECT.

Methods: 48 patients underwent MPI CZT-SPECT and CMR 6 weeks after STEMI, LV parameters were measured with four softwares at MPI CZT-SPECT vs CMR. We evaluated (i) concordance and correlation between MPI CZT-SPECT and CMR, (ii) concordance MPI CZT-SPECT/CMR for the categorical evaluation of the left ventricular dysfunction, and (iii) impacts of perfusion defects > 3 segments on concordance.

Results: LVEF: LCC QGS/CMR = 0.81 [+ 2.2% (± 18%)], LCC MX/CMR = 0.83 [+ 1% (± 17.5%)], LCC 4DM/CMR = 0.73 [+ 3.9% (± 21%)], LCC ECTb/CMR = 0.69 [+ 6.6% (± 21.1%)]. ESV: LCC QGS/CMR = 0.90 [- 8 mL (± 40 mL)], LCC MX/CMR = 0.90 [- 9 mL (± 36 mL)], LCC 4DM/CMR = 0.89 [+ 4 mL (± 45 mL)], LCC ECTb/CMR = 0.87 [- 3 mL (± 45 mL)]. EDV: LCC QGS/CMR = 0.70 [- 16 mL (± 67 mL)], LCC MX/CMR = 0.68 [- 21 mL (± 63 mL], LCC 4DM/CMR = 0.72 [+ 9 mL (± 73 mL)], LCC ECTb/CMR = 0.69 [+ 10 mL (± 70 mL)].

Conclusion: QGS and MX were the two best-performing softwares to evaluate LVEF after recent STEMI.
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http://dx.doi.org/10.1007/s12350-018-01493-yDOI Listing
December 2020

Radiation dosimetry of [ I]ICF01012 in rabbits: Application to targeted radionuclide therapy for human melanoma treatment.

Med Phys 2018 Nov 24;45(11):5251-5262. Epub 2018 Sep 24.

Université Clermont Auvergne, CNRS/IN2P3, Laboratoire de Physique de Clermont, UMR6533, 4 Avenue Blaise Pascal TSA 60026, CS 60026 63178, Aubière Cedex, France.

Purpose: Dosimetry for melanoma-targeted radionuclide therapy (TRT) with [ I]ICF01012, a melanin ligand, has been previously evaluated in mice bearing melanomas. In this study, activity distribution and dosimetry are performed on healthy rabbits (Fauve de Bourgogne) using SPECT-CT imaging and ex vivo measurements.

Material And Methods: Ex vivo biodistribution (i.v. injection: 370 kBq/kg, n = 2 per point) is performed on blood, eyes, brain, lung, liver, kidneys, heart, stomach, and spleen. Dosimetry calculations follow the MIRD formalism: S values are calculated from CT images using the GATE Monte Carlo platform and activity distributions are obtained from SPECT-CT imaging (i.v. injection: 37 MBq/kg n = 3 per point). A specific study is presented to assess dose to human retina.

Results: Time-integrated activities based on SPECT-CT are in accordance with ex vivo measurements except for spleen. Doses to liver and eyes are the most significant, with respectively, 6.38 ± 0.50 Gy/GBq (evaluated through SPECT-CT imaging) and 45.8 ± 7.9 Gy/GBq (evaluated through ex vivo measurements). Characterization of ocular [ I]ICF01012 biodistribution in rabbits and quantification of melanin allowed to assess a dose of 3.07 ± 0.70 Gy/GBq to human retina.

Conclusion: This study sustains [ I]ICF01012 as a good candidate for melanoma TRT and open perspectives for personalized dosimetry calculation during phase I clinical transfer.
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http://dx.doi.org/10.1002/mp.13165DOI Listing
November 2018

Utility of PET/CT in the diagnosis of inflammatory rheumatic diseases: a systematic review and meta-analysis.

Ann Rheum Dis 2018 11 16;77(11):e81. Epub 2017 Nov 16.

Rheumatology Department, Gabriel Montpied Teaching Hospital, Clermont University, Clermont-Ferrand, France.

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http://dx.doi.org/10.1136/annrheumdis-2017-212660DOI Listing
November 2018

Radium 223 dichloride for prostate cancer treatment.

Drug Des Devel Ther 2017 6;11:2643-2651. Epub 2017 Sep 6.

Radiobiology Unit, INSERM U1194, Institut du Cancer de Montpellier (ICM).

Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases. In this review, first we summarize the interplay between prostate tumor cells and bone microenvironment; then, we discuss radium-223 dichloride mechanism of action and present the results of the available clinical trials and future developments for this new drug.
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http://dx.doi.org/10.2147/DDDT.S122417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593411PMC
June 2018

Low-dose dual-isotope procedure planed for myocardial perfusion CZT-SPECT and assessed through a head-to-head comparison with a conventional single-isotope protocol.

J Nucl Cardiol 2018 12 16;25(6):2016-2023. Epub 2017 May 16.

CHRU-Nancy, Université de Lorraine, Department of Nuclear Medicine, 54000, Nancy, France.

Purpose Of The Report: This study aimed at assessing an original low-dose dual-isotope procedure in which the abnormal stress Tc-99m Sestamibi SPECT is followed by rest Tl-201 SPECT, along with a head-to-head comparison with a single-isotope procedure.

Methods And Results: One hundred two patients, referred for a low-dose stress-SPECT with Sestamibi (123 ± 20 MBq) on a CZT camera and for whom a rest Sestamibi SPECT was warranted, had an additional Tl-201 rest-SPECT (52 ± 5 MBq) between stress and rest Sestamibi SPECT recordings. Tl-201 images were processed for spill-over and scatter corrections, and uptake differences with stress Sestamibi SPECT were analyzed: (1) for rest acquisitions from Tl-201 (dual-isotope procedure) and from Sestamibi (single-isotope procedure) and (2) in segments for which a diagnosis of ischemia, infarct, or normal perfusion was achieved. Mean effective dose was 8.3 mSv for dual-isotope but would decrease to 5.7 mSv for an expected rate of 37% of patients for whom rest-SPECT is not warranted. After a further background correction of Tl-201 images, the rest-stress difference in myocardial uptake was equivalent between dual- and single-procedures for identifying ischemic segments (respective areas-under-curves: 0.83 ± 0.03 and 0.81 ± 0.03).

Conclusion: This original dual-isotope procedure provides acceptable radiation doses and consistent results, as compared with conventional single-isotope.
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http://dx.doi.org/10.1007/s12350-017-0914-zDOI Listing
December 2018

99mTc-NTP 15-5 Imaging for Cartilage Involvement in Experimental Rheumatoid Arthritis: Comparison with Routinely Used Molecular Imaging Methods and Sensitivity to Chronic Nonsteroidal Antiinflammatory Drug Treatment.

J Nucl Med 2015 May 3;56(5):798-804. Epub 2015 Apr 3.

Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Clermont-Ferrand, France INSERM, U 990, Clermont-Ferrand, France

Unlabelled: This study determined, using the intraarticular complete Freund adjuvant arthritis mice model, whether the radiotracer (99m)Tc-N-(triethylammonium)-3-propyl-[15]ane-N5 ((99m)Tc-NTP 15-5) targeting proteoglycans has a pathophysiologic validity for in vivo imaging of rheumatoid arthritis (RA) and its response to chronic nonsteroidal antiinflammatory drugs.

Methods: We investigated the time course of cartilage remodeling by (99m)Tc-NTP 15-5 scintigraphy, bone damages by (99m)Tc-hydroxymethylene diphosphonate imaging, inflammation by (18)F-FDG PET, and joint proteoglycan content and pain behavior in animals, without and with meloxicam treatment. Paw circumference, thermal pain behavior, and histology as well as proteoglycan content of the whole joint were determined.

Results: (99m)Tc-NTP 15-5 showed specific tracer accumulation within RA joints, with a significant increase in scintigraphic ratio observed in RA versus shams from day 3 to day 28. (18)F-FDG evidenced uptake in RA joints from day 15 to day 29. Animals treated with meloxicam (5 mg/kg) exhibited a dose-dependent decrease in both (99m)Tc-NTP 15-5 and (18)F-FDG uptake ratios versus saline-treated animals. (99m)Tc-hydroxymethylene diphosphonate bone scans were only positive at day 14 in RA versus shams, with a significant effect of meloxicam. An increase in proteoglycans of RA joint and thermal pain behavior were observed and were dose-dependently reduced by meloxicam.

Conclusion: These experimental results bring data in favor of the (99m)Tc-NTP 15-5 radiotracer for assessing, in vivo, cartilage remodeling in RA that could be used to monitor therapy.
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http://dx.doi.org/10.2967/jnumed.114.151415DOI Listing
May 2015

[¹²³I]ICF01012 melanoma imaging and [¹³¹I]ICF01012 dosimetry allow adapted internal targeted radiotherapy in preclinical melanoma models.

Eur J Dermatol 2015 Jan-Feb;25(1):29-35

Clermont Université, Université d'Auvergne, Imagerie Moléculaire et Thérapie Vectorisée, BP 10448, Inserm, U 990, F-63000 Clermont-Ferrand, France.

Background: Melanin-targeting radiotracers are interesting tools for imaging and treatment of pigmented melanoma metastases. However, variation of the pigment concentration may alter the efficiency of such targeting.

Objectives: A clear assessment of both tumor melanin status and dosimetry are therefore prerequisites for internal radiotherapy of disseminated melanoma.

Materials & Methods: The melanin tracer ICF01012 was labelled with iodine-123 for melanoma imaging in pigmented murine B16F0 and human SK-Mel 3 melanomas.

Results: In vivo imaging showed that the uptake of [(123)I]ICF01012 to melanomas correlated significantly with melanin content. Schedule treatment of 3 × 25 MBq [(131)I]ICF01012 significantly reduced SK-Mel 3 tumor growth and significantly increased the median survival in treated mice. For this protocol, the calculated delivered dose was 53.2 Gy.

Conclusion: Radio-iodinated ICF01012 is a good candidate for both imaging and therapeutic purposes for patients with metastatic pigmented melanomas.
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http://dx.doi.org/10.1684/ejd.2014.2481DOI Listing
January 2016

(123)I-BZA2 as a melanin-targeted radiotracer for the identification of melanoma metastases: results and perspectives of a multicenter phase III clinical trial.

J Nucl Med 2014 Jan 21;55(1):15-22. Epub 2013 Nov 21.

Nuclear Medicine, Jean Perrin Cancer Center, Clermont-Ferrand, France.

Unlabelled: Our group has developed a new radiopharmaceutical, (123)I - N-(2-diethylaminoethyl)-2-iodobenzamide ((123)I-BZA2), a benzamide derivative able to bind to melanin pigment in melanoma cells. In a prospective and multicentric phase III clinical study, the value of (18)F-FDG PET/CT and (123)I-BZA2 scintigraphy was compared for melanoma staging.

Methods: Patients with a past history of cutaneous or ocular melanoma were included from 8 hospitals. (18)F-FDG imaging was performed according to a standard PET protocol. Whole-body, static planar, and SPECT/CT (if available) images were acquired 4 h after injection of a 2 MBq/kg dose of (123)I-BZA2. (18)F-FDG and (123)I-BZA2 sensitivity and specificity for the diagnosis of melanoma metastasis were calculated and compared on both a lesion basis and a patient basis. True-positive and true-negative lesion status was determined after 6 mo of clinical follow-up or according to lesion biopsies (if available). Melanin content in biopsies was evaluated with the standard Fontana-Masson silver method and was correlated with (123)I-BZA2 uptake. Based on statistical analysis, the number of inclusions was estimated at 186.

Results: In all, 87 patients were enrolled from 2008 to 2010. Of these, 45 (52%) had metastases. A total of 338 imaging abnormalities were analyzed; 86 lesions were considered metastases, and 20 of 25 lesion biopsies found melanoma metastases. In a patient-based analysis, the sensitivity of (18)F-FDG for diagnosis of melanoma metastases was higher than that of (123)I-BZA2, at 87% and 39%, respectively (P < 0.05). For specificity, (18)F-FDG and (123)I-BZA2 were not statistically different, at 78% and 94%, respectively. In a lesion-based analysis, the sensitivity of (18)F-FDG was statistically higher than that of (123)I-BZA2 (80% vs. 23%, P < 0.05). The specificity of (18)F-FDG was lower than that of (123)I-BZA2 (54% vs. 86%, P < 0.05). According to biopsy analysis, only 9 of 20 metastatic lesions (45%) were pigmented with high melanin content. (123)I-BZA2 imaging was positive for 6 of 8 melanin-positive lesions, fairly positive for 3 of 10 melanin-negative lesions, and negative for 7 of 10 melanin-negative lesions. The sensitivity and specificity of (123)I-BZA2 for the diagnosis of melanin-positive lesions were 75% and 70%, respectively. Because of a low (123)I-BZA2 sensitivity, this clinical trial was prematurely closed after 87 patients had been included.

Conclusion: This study confirms the value of (18)F-FDG PET/CT for melanoma staging and strengthens the high accuracy of (123)I-BZA2 for diagnosis of melanin-positive metastatic melanoma. Moreover, benzamide derivatives radiolabeled with therapeutic radionuclide may offer a new strategy for the treatment of metastatic melanoma patients harboring melanin-positive metastases.
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http://dx.doi.org/10.2967/jnumed.113.123554DOI Listing
January 2014

Differential diagnosis of trampoline fracture from osteomyelitis by bone scan with pinhole collimator.

Ann Nucl Med 2014 Feb 18;28(2):163-6. Epub 2013 Sep 18.

Department of Nuclear Medicine, Institut Curie, 35 rue Dailly, 92210, Saint-Cloud, France,

A 2-year-old girl with recent history of trampoline fall presented to the A&E Department for complete functional impairment of the left lower extremity and fever. Blood examination revealed an inflammatory syndrome, while plain radiographs were normal. As magnetic resonance imaging was unavailable, a bone scintigraphy was performed. While standard acquisition found an intense uptake focused on the left proximal tibial metaphysis whose appearance was suggestive of acute hematogenous osteomyelitis, complementary acquisition with the pinhole collimator demonstrated that this abnormal uptake was clearly distinct from the cartilage growth plate. One month follow-up radiographs showed a fracture that confirmed the diagnosis of trampoline fracture.
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http://dx.doi.org/10.1007/s12149-013-0770-0DOI Listing
February 2014

Interobserver agreement of qualitative analysis and tumor delineation of 18F-fluoromisonidazole and 3'-deoxy-3'-18F-fluorothymidine PET images in lung cancer.

J Nucl Med 2013 Sep 5;54(9):1543-50. Epub 2013 Aug 5.

Nuclear Medicine and Radiotherapy, Henri Becquerel Cancer Center and Rouen University Hospital, and QuantIF-LITIS (EA [Equipe d'Accueil] 4108), Faculty of Medicine, University of Rouen, Rouen, France.

Unlabelled: As the preparation phase of a multicenter clinical trial using (18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), (18)F-fluoromisonidazole ((18)F-FMISO), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods.

Methods: Ten (18)F-FDG, ten (18)F-FMISO, and ten (18)F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and κ. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV).

Results: For uptake intensity, the κ values between centers were, respectively, 0.59 for (18)F-FDG, 0.43 for (18)F-FMISO, and 0.44 for (18)F-FLT using the 5-level scale; the values were 0.81 for (18)F-FDG and 0.77 for both (18)F-FMISO and (18)F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for (18)F-FMISO and 0.2 and 0.3, respectively, for (18)F-FLT. The segmentation methods yielded significantly different volumes for (18)F-FMISO and (18)F-FLT (P < 0.001). In comparison with physicians, the best method found was 1.5 × maximum SUV (SUVmax) of the aorta for (18)F-FMISO and 1.3 × SUVmax of the muscle for (18)F-FLT. The methods using the SUV of 1.4 and the method using 1.5 × the SUVmax of the aorta could be used for (18)F-FMISO and (18)F-FLT. Moreover, for (18)F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6 × muscle SUVmax) could be used.

Conclusion: The reproducibility of the visual analyses of (18)F-FMISO and (18)F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the (18)F-FMISO and (18)F-FLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased (18)F-FMISO or (18)F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4).
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http://dx.doi.org/10.2967/jnumed.112.118083DOI Listing
September 2013

Case of thyroid involvement by multiple myeloma.

J Clin Oncol 2013 Jul 10;31(21):e380-2. Epub 2013 Jun 10.

Department of Nuclear Medicine, Cancer Center Jean Perrin, 58 rue Montalembert, 63011 Clermont-Ferrand, France.

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http://dx.doi.org/10.1200/JCO.2012.44.1907DOI Listing
July 2013

Incidental scintigraphic finding of ovarian teratoma containing normal thyroid tissue on post-radioactive iodine therapy for papillary thyroid cancer.

Clin Nucl Med 2013 Jun;38(6):467-8

Nuclear Medicine Department, Jean Perrin Center, 58 rue Montalambert, 63000 Clermont-Ferrand, France.

Abnormal focal uptakes are often visualized on I post-treatment scintigraphy in case of differentiated thyroid carcinoma. For some of these, especially on atypical localization, it can be difficult to affirm the benign or malignant nature. A high serum thyroglubulin value after surgery may suggest the presence of metastatic disease. We report a case of an abnormal ovarian uptake on post-treatment scintigraphy associated with an elevated thyroglobulin value revealing finally an ovarian mature cystic teratoma containing normal thyroid tissue.
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http://dx.doi.org/10.1097/RLU.0b013e318286bdbcDOI Listing
June 2013

Early detection and longitudinal monitoring of experimental primary and disseminated melanoma using [¹⁰F]ICF01006, a highly promising melanoma PET tracer.

Eur J Nucl Med Mol Imaging 2012 Sep 16;39(9):1449-61. Epub 2012 Jun 16.

Imagerie Moléculaire et Thérapie Vectorisée, Clermont Université, Université d'Auvergne, BP 10448, 63000 Clermont-Ferrand, France,

Purpose: Here, we report a new and rapid radiosynthesis of (18)F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([(18)F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma.

Methods: [(18)F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous (lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [(18)F]ICF01006 were evaluated at different stages of tumoural growth and compared to (18)F-fluorodeoxyglucose ([(18)F]FDG).

Results: The fully automated radiosynthesis of [(18)F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [(18)F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [(18)F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [(18)F]FDG showed that both radiotracers were able to detect melanoma lesions, but [(18)F]ICF01006 was superior in terms of contrast and specificity.

Conclusion: Our promising results provide further preclinical data, reinforcing the excellent potential of [(18)F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma.
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http://dx.doi.org/10.1007/s00259-012-2168-yDOI Listing
September 2012

First ex vivo study demonstrating that 99mTc-NTP 15-5 radiotracer binds to human articular cartilage.

Eur J Nucl Med Mol Imaging 2011 Nov 4;38(11):2077-82. Epub 2011 Aug 4.

Nuclear Medicine Department, Jean Perrin Cancer Centre, Clermont-Ferrand, France.

Purpose: Preclinical data pointed to (99m)Tc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify (99m)Tc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone (99m)Tc-hydroxymethylene diphosphonate (HMDP) radiotracer.

Methods: Three osteoarthritic human tibial plateaux and four tibiofemoral joints were incubated with (99m)Tc-NTP 15-5 and (99m)Tc-HMDP for 2 h. Affinity of tracers for cartilage was determined by visual analysis of SPECT/CT acquisitions and measurement of cartilage to cortical bone uptake ratios.

Results: Cartilage to cortical bone uptake ratios were 3.90 ± 2.35 and 0.76 ± 0.24, respectively, for (99m)Tc-NTP 15-5 and (99m)Tc-HMDP radiotracers. Visual analysis of fused SPECT/CT slices showed selective, intense (99m)Tc-NTP 15-5 accumulation in articular cartilage, whereas (99m)Tc-HMDP binding was low. Interestingly, a cartilage defect visualized on CT was clearly associated with focal decreased uptake of (99m)Tc-NTP 15-5.

Conclusion: The tracer (99m)Tc-NTP 15-5 is of major interest for human cartilage molecular imaging and could find clinical applications in osteoarthritis staging and monitoring.
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http://dx.doi.org/10.1007/s00259-011-1890-1DOI Listing
November 2011

Rest and low-dose dobutamine Tc-99m-mibi gated-SPECT for early prediction of left ventricular remodeling after a first reperfused myocardial infarction.

J Nucl Cardiol 2009 Jul-Aug;16(4):597-604. Epub 2009 May 29.

Department of Cardiology, Gabriel Montpied University Hospital, Clermont-Ferrand, France.

Background: Left ventricular (LV) remodeling after myocardial infarction (MI) occurs frequently despite successful percutaneaous coronary intervention (PCI) but cannot be predicted by simple clinical parameters.

Methods And Results: This prospective study tested the value of rest and low-dose dobutamine (LDD) Tc-99m-mibi gated-SPECT for early prediction of LV remodeling in patients treated by PCI in the acute phase of a first MI. Infarct size, infarct severity, regional wall motion abnormality (RWMA), and wall thickening score (WTs) were assessed at rest and on LDD by SPECT 6 +/- 2 days after MI in 40 patients. LV remodeling was defined as 20% increase at 6 months in LV end-diastolic volume assessed by MRI. Infarct severity at rest showed the best predictive values for left remodeling (PPV: 86%, NPV: 88%, accuracy: 88%; AUC: 0.750). Functional parameters at neither rest nor LDD study further improved predictive values of the SPECT imaging.

Conclusions: Infarct severity assessed by Tc-99m-sestamibi gated-SPECT performed in the subacute phase of a first STEMI predicts LV remodeling with high accuracy without incremental value nor of functional parameters nor of LDD. Therefore, our results suggest that LDD should not be used in this setting.
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http://dx.doi.org/10.1007/s12350-009-9098-5DOI Listing
December 2009

Effect of thrombus aspiration on infarct size and left ventricular function in high-risk patients with acute myocardial infarction treated by percutaneous coronary intervention. Results of a prospective controlled pilot study.

Am Heart J 2009 Mar 4;157(3):583.e1-7. Epub 2009 Feb 4.

Department of Cardiology, G. Montpied University Hospital, Clermont-Ferrand, France.

Background: Thrombus aspiration devices have been shown to improve reperfusion criteria and to reduce distal embolization in patients treated by percutaneous coronary interventions (PCI) in the acute phase of ST-elevation myocardial infarction (STEMI). There are, however, little data about their efficacy in the reduction of infarct size.

Methods: We sought to assess in a prospective randomized trial the impact of thrombus aspiration on infarct size and severity and on left ventricular function in high-risk patients with a first STEMI. The primary end point was scintigraphic infarct size, and secondary end points were infarct severity and regional and global left ventricular function. Forty-four patients with completely occluded (Thrombolysis in Myocardial Infarction flow 0-1) proximal segments of infarct-related artery were randomly assigned to thrombus aspiration group with the Export catheter (n = 20) (Medtronic, Inc, Minneapolis, MN) or PCI-only group. A rest Tc-99-mibi gated single-photon emission computed tomographic and contrast-enhanced magnetic resonance imaging were performed 6 +/- 2 days later.

Results: Infarct size was comparable in patients in the thrombus aspiration group and PCI-only group (30.6% +/- 15.8% vs 28.5% +/- 17.9% of the left ventricle, P = .7) as was infarct severity in infarct-related artery territory (55% +/- 12% vs 55% +/- 14%, P = .9). Transmurality score as assessed by magnetic resonance imaging was similar in both groups (2.03 +/- 1.05 vs 2.16 +/- 1.21, P = .7). There was no impact of thrombus aspiration on other secondary end points.

Conclusion: In our study, thrombus aspiration with the Export catheter performed as adjunctive therapy in high-risk patients with total occlusion of the proximal part of major coronary arteries does not decrease infarct size or severity and has no effect on left ventricular regional and global function.
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http://dx.doi.org/10.1016/j.ahj.2008.11.017DOI Listing
March 2009