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Introduction Dual phase 18 FDG brain PET is helpful to assess brain metastases (BM) as tracer will build up in metastases or tumor recurrences while its retention remains stable within normal tissue or inflammatory processes. This is useful when MRI can’t discriminate brain tumor recurrence (TR) rom radionecrosis (RN) after stereotaxic radiosurgery (SRS) for BM. Many studies have sought to improve diagnostic performance by associating FDG-PET and MRI with interesting results but many biases, mostly within image post-processing. Coregistered MRI and dual phase FDG-PET images could alleviate these biases and be used to extract prognostic biomarkers. Materials and methods We retrospectively evaluated patients treated with SRS for BM which developed a contrast-enhanced MRI lesion with non-conclusive diagnosis for TR or RN. All patients underwent MRI and FDG-PET at least 3 months after their last SRS session. Dual FDG-PET consisted in an “early” and “delayed” acquisition, respectively 30 minutes and 4 h after injection. MRI included permeability and perfusion sequences. PET and MRI data were all coregistered on the contrast enhanced T1 MRI images. Semi-automated Volumes of Interest (VOI) of the tumor were drawn on the BM and a reference contralateral white-matter ROI (WM) was drawn for standardization; every metric was calculated inside these ROIs, in particular the tumor SUVmax and its variation in time. A 20% increase in the tumor SUVmax was in favor of TR while a modification of less than 100% was in favor of RN. Imaging metrics were then evaluated for their association with TR or RN based on histological, radiological and clinical criteria after at least 6 months follow-up. Results Nine patients were ruled out as TR and 6 as RN. After standardization, there was a significant difference between groups for VP (P = 0.042), Washin (P = 0.035), Peak Enhancement (P = 0.037), standardized delayed SUVmax (P = 0.008) and RI (P = 0.016). Semi-quantitative analysis found respectively for PET and MRI a Sensitivity of 100% and 87.5% and a Specificity of 100% and 85.71%. Conclusion Coregistered PET-MRI images accurately discriminate between TR and RN. With FDG being the most commonly used PET radiotracer, this protocol remains easily transposable and should be encouraged to obtain non-invasive prognostic and clinically relevant biomarkers.

18F-FDG PET is recommended for the initial staging of locally advanced breast cancer. Studies have shown the prognostic value of 18F-FDG PET for staging, but its ability to predict pathological complete response remains uncertain. Our objective was to determine the predictive value of early therapeutic evaluation by 18F-FDG PET for HER2-positive breast cancer patients. We studied a subpopulation of the prospective and multicentric French NeoTOP trial, at interim analysis. All patients were eligible for neoadjuvant chemotherapy. A 18F-FDG PET was performed at baseline and then after one cycle of neoadjuvant treatment. 18F-FDG PET were studied by three conventional methods (two visuals and one quantitative) and by textural analysis. Complete pathological response on surgical samples corresponded to grades 1/2 of Chevallier's classification and no responders corresponded to grades 3/4 of Chevallier. Pathological results were available for 21 patients. SUVmax decreased by 55% after one cycle of chemotherapy. No difference between groups was found with visuals, conventional quantitative and textural analysis of tumour uptake evaluations. Early therapeutic evaluation by 18F-FDG PET for HER2-positive breast cancer was not predictive of pathological therapeutic response after neoadjuvant treatment, with conventional study or textural analyses in this interim analysis.

Since the beginning of the year 2020, the coronavirus-19 disease (COVID-19) pandemic has undoubtedly posed significant challenges to healthcare systems worldwide. It has also affected, in a way previously unimaginable, our lifestyle and the way we relate to each other, not only at work, but also in the community and in the family setting. Healthcare systems worldwide have been forced to make huge alterations to be able to handle the different stages of the pandemic. [...]

Introduction Dual phase 18[F]-FDG brain PET (dual-PET) is useful to distinguish tumor recurrence (TR) from radionecrosis (RN) after stereotaxic radiosurgery (SRS) of brain metastases, when contrast-enhanced MRI is inconclusive. We aimed to compare six different visual and quantitative interpretation criteria to enhance diagnostic performances. Materials and methods In this retrospective french multicentric study (Clermont-Ferrand, Montpellier, Rennes), we evaluated 45 patients previously treated with SRS for BM, addressed for a dual-PET by the local neuro-oncological committees for an evolving lesion on MRI inconclusive between TR and RN, at least 3 months after the last SRS session. Dual-PET included both an “early” and a “delayed” acquisition, respectively 30 to 60 minutes and 4 to 5 hours after 18[F]-FDG injection. After measuring SUVmax values of both lesion (L) and mirror contralateral grey matter (GM) at early (1) and delayed (2) acquisitions, three quantitative metrics were calculated: ratios of L SUVmax to GM SUVmax at “early” (L1/GM1) and “delayed” (L2/GM2) acquisitions and the retention index which is the variation over time of the standardized SUVmax ratio (RI = [(Delayed-Early)/Early]). Visual analysis was also conducted using a subjective 6 points visual scale of the lesion uptake at both acquisitions. The five interpretation criteria were compared according to their area under the ROC curve (AUC), and to their diagnostic accuracy applying the best cut off value (maximizing the Youden's index) by the Cochran Q test. The final diagnosis was based on pathology, or by default radiological and clinical follow-up criteria after at least 6 months. Results Final diagnoses were TR for 24 patients and RN for 21 patients. There was no statistically significant difference regarding AUC between the different interpretation methods. AUC ranged from 0,78 [95 %CI 0,63; 0,89] with the L1/GM1 Ratio, to 0.85 [95 %CI 0.72; 0.94] with the L2/GM2 ratio. Visual analyses AUC were excellent at both early (0.835 [95 %CI 0.7; 0.93]) and delayed acquisitions (0.83 [95 %CI 0.69; 0.92]). There was no statistically significant difference between accuracies (p = 0.87) ranging from 0.71 with the RI ratio to 0.80 with both the “delayed” visual and quantitative analyses. Conclusion Dual-PET protocol distinguishes RN and TR after SRS with robust diagnostic performances in case of doubtful MR, with an accuracy up to 80 %.

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 Federation 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 Societe francaise de medecine nucleaire, 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.

International audience; 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.

Introduction: 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.Methods: This retrospective study included 140 patients who underwent [18F]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.Results: 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.Conclusion: 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.

PURPOSE This study aims to perform dosimetry for [99m 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. [99m 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 [99m 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.

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.

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 [18F]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. [18F]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, [18F]ML-10 was rapidly cleared from the nontarget organs and mainly eliminated by the kidneys. Comparison of the in vivo [18F]FDG, [18F]FMISO, and [18F]ML-10 uptakes revealed that the tumor accumulation of [18F]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 [18F]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 [18F]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.

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.

Purpose: The objective of this study was to evaluate periarticular FDG uptake scores from 18F-FDG-PET/CT to identify polymyalgia rheumatica (PMR) within a population presenting rheumatic diseases. Methods: A French retrospective study from 2011 to 2015 was conducted. Patients who underwent 18F-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. Results: Among 222 18F-FDG PET/CT selected for 215 patients, 161 18F-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]). Conclusions: This study suggests that 18F-FDG PET/CT had good performances to identify PMR within a population presenting rheumatic diseases.

International audience; 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.

Purpose For differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([18F]FDG) dual time point PET could be helpful. Albeit [18F]FLT is more specific for tumors than [18F]FDG; we explored the role of dual time point [18F]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 [18F]FLT injection. Semiquantitative analyses of [18F]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 [18F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.

International audience; Introduction: 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. Patients and Methods: 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. Results: 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]; p < 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 (p = 0.54), confirming the limited value of ad-RAI. Conclusion: 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.

Objectives Dual phase 18 FDG-PET has been proven helpful to assess FDG-avid cerebral tumors as tracer will build up in metastases or tumor recurrences while its retention remains stable within normal tissue or inflammatory process. This is useful when MRI can’t discriminate brain tumor recurrence (TR) from radionecrosis (RN) after stereotaxic radiosurgery (SRS) for brain metastases (BM). Many studies sought to improve diagnostic performance by associating FDG-PET and MRI with interesting results but many bias, mostly within image post-processing. Coregistered MRI and dual phase FDG-PET images could alleviate these biases and be used to extract prognostic biomarkers. Methods We retrospectively evaluated patients treated with SRS for BM which developed a contrast-enhanced MRI lesion with non-conclusive diagnosis for TR or RN. All patients underwent MRI and FDG-PET at least 3 months after their last SRS session. Dual FDG-PET comprised a one hour “based image” (H1) followed by a 4 hours “delayed image” (H4). MRI included contrast enhanced T1 (T1), FLAIR, ASL (BAT,CBF), T1 Perfusion (ktrans, SER) and T2* Permeability (k2, rBF, rBV). PET and MRI data were all coregistered on the T1 images. Semi-automated Regions of Interest (ROI) of the tumor were drawn on the T1 MRI, H1 and H4 FDG-PET images; a reference contralateral white-matter ROI (WM) was drawn for standardization. Imaging metrics were then evaluated for their association with TR or RN based on histological, radiological and clinical criteria after at least 6 months follow-up. Results Eleven patients matched the inclusion criteria; 7 with TR and 4 with RN; no additional treatment was introduced. On visual analysis, FDG-PET and MRI respectively obtained 100% and 83% Sensitivity and 100% and 80% Specificity. The two MRI-false negative diagnoses were subsequently identified on follow-up (1 patient, RN) and histology (1 patient, TR). When standardized on WM, PET SUVmax values were significantly different across groups at H1 (P Conclusion Coregistered PET-MRI images accurately discriminates between TR and RN. With FDG being the most commonly used PET radiotracer, this protocol remains easily transposable and should be encouraged to obtain non-invasive prognostic and clinically relevant biomarkers.

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. 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. 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)]. QGS and MX were the two best-performing softwares to evaluate LVEF after recent STEMI.

Purpose Dosimetry for melanoma-targeted radionuclide therapy (TRT) with [131 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 [131 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 [131 I]ICF01012 as a good candidate for melanoma TRT and open perspectives for personalized dosimetry calculation during phase I clinical transfer.

This study determined, using the intraarticular complete Freund adjuvant arthritis mice model, whether the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-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 99mTc-NTP 15-5 scintigraphy, bone damages by 99mTc-hydroxymethylene diphosphonate imaging, inflammation by 18F-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:99mTc-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. 18F-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 99mTc-NTP 15-5 and 18F-FDG uptake ratios versus saline-treated animals. 99mTc-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 99mTc-NTP 15-5 radiotracer for assessing, in vivo, cartilage remodeling in RA that could be used to monitor therapy.

In an article published in the Annals of the Rheumatic Diseases , Schonau et al suggested that positron emitted tomography (PET)/CT is useful in determining the cause of unexplained fever/inflammation.1 In this letter, we wish to add further data to support the conclusions of this article. More and more, PET/CT is used to determine the cause of fever, systemic inflammation or atypical or resistant rheumatic disease. However, the utility of PET/CT in these diagnoses is not clear. Thus, we performed a meta-analysis to investigate the utility of PET/CT in the diagnosis of inflammatory rheumatic diseases. We searched MEDLINE to identify all reports of interest published prior to June 2016 using the search terms: ‘(PET scan OR …

We report the case of a 70-year-old man who underwent an 18[F]-Fluorocholine ([18F]-FCH) positron emission tomography combined with computed tomography (PET/CT) after biochemical recurrence of prostate cancer previously treated by prostatectomy in 2012 (Gleason score 5 [2 + 3], PSA value before prostatectomy 19 ng/mL). Early acquisitions centered on the pelvis following the injection of 258 MBq of [18F]-FCH showed a rectal focused and intense uptake. The imaging performed 60 minutes after injection from the base of the skull to the upper third of the femur confirmed the presence of this focal uptake related on CT slices to a thickening of the rectal wall. Biopsies of the corresponding lesion allowed the diagnosis of well-differentiated rectal adenocarcinoma. The patient was directed to surgical resection, which was effective in September 2014. Pathology analysis was in favor of a well-differentiated rectal adenocarcinoma invaded the totality of the rectal wall. Fifteen lymph nodes were dissected and were benign. The tumor was classified as T3N0 (UICC 2010 classification). A contrast enhancement CT scan did not show any lesion compatible with rectal cancer metastasis. More and more incidental findings will occur in clinical PET/CT practice. If there are suspicious lesions of a different etiology than that announced in the request, nuclear medicine physicians must be aware of such issues in order to help clinicians to pursue further investigations like endoscopic biopsy for colorectal uptake. Finally, further studies must be performed to confirm the usefulness of [18F]-FCH PET/CT in colorectal cancer compared to [18F]-FDG PET/CT.

Emmanuel Deshayes,1,2 Mathieu Roumiguie,3 Constance Thibault,4 Philippe Beuzeboc,5 Florent Cachin,6 Christophe Hennequin,7 Damien Huglo,8 François Rozet,9 Diana Kassab-Chahmi,10 Xavier Rebillard,11 Nadine Houédé1,12 1Radiobiology Unit, INSERM U1194, Institut du Cancer de Montpellier (ICM), 2Department of Nuclear Medicine, Institut du Cancer de Montpellier (ICM), Montpellier, 3Urology Department, Andrology and Renal Transplantation, CHU Rangueil, Toulouse, 4Medical Oncology Department, Hôpital Européen Georges Pompidou, 5Oncology Department, Institut Curie, 6Department of Nuclear Medicine, CHU, Clermont-Ferrand, 7Radiotherapy Department, Hôpital Saint Louis, Paris, 8Department of Nuclear Medicine, CHRU, Lille, 9Urology Department, Institut Mutualiste Montsouris, 10Intergroupe coopérateur francophone de recherche en onco-urologie, Paris, 11Urology Department, Clinique BeauSoleil, Montpellier, 12Medical Oncology Department, Institut de Cancérologie du Gard – CHU Caremeau, Nîmes, France Abstract: 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 acalcium-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. Keywords: bone metastasis, mCRPC, mechanism, drug, agents, development&nbsp

A PET/CT performed for a 70-year-old patient initially addressed for lung cancer staging demonstrated an unexpected moderate intensity 18F-FDG uptake in front of bilateral soft tissue masses localized between the inferior tips of the scapulae and the chest. CT imaging was diagnostic with typical features of elastofibroma dorsi (ED). ED is a rare fibroelastic benign tumor however of interest to diagnose on PET/CT to avoid unnecessary biopsy or other investigation.

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.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).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 (P0.001). 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.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).

Purpose Here, we report a new and rapid radiosynthesis of 18F-N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([18F]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.

Following the article of Alberti et al., we would like to provide our own experience with two more cases in evaluation of POEMS syndrome using morphological and functional imaging modalities, including plain X-rays, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy and positrons emission tomography with computed tomography (PET/CT). Among them, 18-FDG PET/CT proved its usefulness allowing extensive screening of the bony lesions involved.

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.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.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.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.

Resume La medecine nucleaire a connu ces dix dernieres annees de profondes evolutions avec l’arrivee des tomographes par emission de positons et des tomographes monophotoniques couples au scanner. L’utilisation recente dans notre service de la camera a semi-conducteurs D-Spect (Spectrum Dynamics, Israel) devrait constituer un nouveau tournant dans notre pratique clinique. Cette nouvelle technologie permet en effet une amelioration de la resolution des images et grâce a une augmentation de la sensibilite de detection, des acquisitions plus rapides et une diminution des activites injectees. Cette camera actuellement dediee a la cardiologie nucleaire presente, par ailleurs, un systeme original de collimation et de reconstruction des images. Nous relatons dans cet article notre experience clinique de l’utilisation de la D-Spect, dans le cadre d’une etude preliminaire dont l’objectif est la comparaison des resultats avec ceux obtenus sur une camera conventionnelle.

Intraoperative imprint cytology (IC) is one of several accurate, proven methods to detect tumor cells in sentinel lymph nodes (SLN) from patients with operable breast cancer. In patients treated with neoadjuvant chemotherapy (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy procedure. We evaluated the validity of IC for SLN testing in patients after NAC. Patients with infiltrating breast carcinoma receiving NAC (n = 132) were studied prospectively. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. SLN were evaluated using IC in 80 of 132 patients (60%). The results of IC in the adjuvant setting (100 patients) were used for comparison. SLN metastases were correctly identified using IC in 58 of 80 (72%) patients. False negative results were observed in 21 patients. The sensitivity of IC testing was 38.2% and specificity 97.8%. The positive and negative predictive values (PPV and NPV) were 92.9% and 68.2%, respectively. In univariate analysis and multivariate logistic regression analysis, patients with micrometastases or isolated tumor cells in SLN have 2.3 times higher risk of a false negative IC result than patients with macrometastases in SLN (P = .00021; relative risk [RR] = 2.3; 95% confidence interval, 1.37–3.85). The non-NAC group, which contained fewer micrometastatic cases, showed better sensitivity (47.4%) and NPV (88.9%). NAC does not seem to influence the accuracy and sensitivity of IC. Variations in sensitivity are related to the proportion of cases with micrometastases and ITC, as it was also shown in chemonaive patients.

The particular status of radiopharmaceuticals, together with the positioning of nuclear medicine in multidisciplinary approach of oncology, lead to real difficulties for conception, validation and granting of clinical trials which are necessary for demonstrating clinical interest of new compounds, for diagnosis as well as for therapeutic use. This article is a presentation of some recent clinical trials conducted in nuclear medicine in France, showing its dynamism but also pointing out some encountered difficulties. These experiences could lead to reflexion in order to improve the clinical research performances, taking into account a scientific and regulatory context more and more constraining.

La plupart des programmes de recherche sur les nouveaux radiopharmaceutiques portent actuellement sur les traceurs utilises en tomographie par emission de positons (TEP). Seules quelques equipes continuent a travailler sur des nouveaux traceurs non fluores. Toutefois, l'arrivee des gammas cameras TEMP/TDM et le fremissement des cameras a semi-conducteur, pourraient donner un nouvel elan au developpement des traceurs non TEP. Nous exposons dans cet article l'experience acquise par notre laboratoire dans la conception et l'etude de deux nouvelles familles de molecules non fluorees. Le 99m Tc-NTP 15-5 se lie sur les proteoglycanes et pourrait ainsi etre utilise pour le diagnostic ou suivi de l'arthrose et du chondrosarcome. Les iodobenzamides, traceurs de la melanine, sont actuellement compares au 18 F-fluorodeoxyglucose dans un essai de phase III pour le suivi et le diagnostic de metastases de melanome. Nos derniers travaux portent sur de nouveaux analogues heterocycliques utilisables pour le traitement du melanome.

Resume But . – Evaluer l’interet de la TEP-TDM au 18 F-fluoro-2-desoxyglucose (FDG) et de la mesure du standardized uptake value maximal (SUV max ) de la tumeur primitive au stade diagnostique pour la determination du statut ganglionnaire des patientes atteintes de cancer du col uterin. Materiel et methodes . – Il s’agit d’une etude retrospective portant sur 18 patientes ayant beneficie d’une TEP-TDM et d’une IRM au stade pretherapeutique pour une tumeur du col uterin de stade superieur ou egal a IB selon Figo. Le SUV max tumoral de chaque patiente a ete mesure retrospectivement. Tous les sujets ont beneficie d’une radiochimiotherapie premiere ; une preuve histologique du statut ganglionnaire a ete obtenue dans 12 des 18 cas. Resultats . – La sensibilite et la specificite de la TEP-TDM pour la determination du statut ganglionnaire ont ete evaluees respectivement a 80 et 86 %, en considerant les patientes globalement les sensibilite et specificite de l’IRM etant dans ces conditions de 80 et 71 %. Dans 16,6 % des cas, la TEP-TDM a detecte des lesions sus-diaphragmatiques meconnues. Le SUV max tumoral des patientes du groupe N+ en TEP-TDM etait de 15,6 ± 1,6 contre 8,5 ± 3,9 pour celui du groupe N− ( p max a ete determine au-dela duquel la probabilite d’avoir une atteinte ganglionnaire en TEP-TDM est nettement superieure. Conclusion . – Au stade diagnostique, le SUV max d’une tumeur primitive du col uterin semble predictif du statut ganglionnaire en TEP-TDM. Une etude prospective permettrait de determiner si la valeur predictive de cette quantification est suffisante pour motiver une intensification du traitement chez les patientes dont le SUV max tumoral est superieur au seuil 10,8 identifie comme le plus discriminant au cours de cette etude.

In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC.Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method.The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 successfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; P = 0.045) and positive clinical nodal status (N0 versus N1-N2; P = 0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy.Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation.

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. A clear assessment of both tumor melanin status and dosimetry are therefore prerequisites for internal radiotherapy of disseminated melanoma. The melanin tracer ICF01012 was labelled with iodine-123 for melanoma imaging in pigmented murine B16F0 and human SK-Mel 3 melanomas. In vivo imaging showed that the uptake of [123I]ICF01012 to melanomas correlated significantly with melanin content. Schedule treatment of 3 × 25 MBq [131I]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. Radio-iodinated ICF01012 is a good candidate for both imaging and therapeutic purposes for patients with metastatic pigmented melanomas.

The aim of this study was to evaluate an automatic method based on a computed tomography (CT) derived region of interest (ROI) to quantify the mean standardized uptake value (SUVm) of 18 F-fluoro-deoxy-glucose (FDG) in pulmonary lesions detected by positron emission tomography (PET). A total of 164 pairs of slices were selected in a series of PET/CT studies performed in 26 patients presenting lung tumours of various forms and complexities. On each matched CT slice, a ROI was obtained by growth-region segmentation starting from a pixel contained in the tumour. The obtained ROI was then applied to the PET image to calculate SUVm. Results were compared with the conventional manual method using a geometric ROI positioned directly on the PET lesion. The automatic delineation of the tumour from the CT image was successful in 136 sections (83%). The SUVm calculated by the manual and automatic method were respectively (mean±standard deviation) 5.05±2.39 and 6.70±3.18 ( p p

Purpose This study examines the use of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the evaluation of the therapeutic response for patients treated with high-dose chemotherapy (HDC) with autologous stem cell transplantation for metastatic breast cancer (MBC) focusing on prognostic stratification. Patients and Methods Forty-seven patients with MBC were treated with a maximum of three cycles of HDC. Therapeutic response was assessed with conventional imaging (CImg; including a computed tomography in all cases and ultrasound, mammography, and bone scanning as clinically indicated) and by FDG-PET study performed after the last cycle of HDC. Parameters analyzed for predicting survival were FDG-PET and CImg results, pattern of disease, prior treatment, and HDC regimen. Results Complete responses were observed in 16 patients (37%) with CImg and 34 patients (72%) with FDG-PET. The FDG-PET result was the most powerful and independent predictor of survival; patients with a negative post-treatment FDG-PET had a longer median survival than patients with a positive FDG-PET (24 months v 10 months; P < .001). By multivariate analysis the relative risk (RR) of death was higher in patients with FDG-PET-positive disease (RR, 5.3), prior anthracycline treatment (RR, 3.3), or with visceral metastasis (RR, 2.4). Conclusion A single FDG-PET study performed after completion of HDC for MBC can powerfully stratify for survival. This may have implications for how we should assess outcome after conventional-dose therapy for MBC and warrants additional study.

The purpose of this study was to assess the value of technetium 99m sestamibi gated single photon emission computed tomography (SPECT) in predicting the evolution of left ventricular volumes in patients treated successfully in the acute phase of a myocardial infarction (MI).Twenty-nine patients with acute MI and early percutaneous transluminal coronary angioplasty (PTCA) were included in this study. A rest Tc-99m sestamibi electrocardiography (ECG)-gated SPECT study was performed 21 +/- 5 days after PTCA. The myocardial perfusion index was calculated by use of a semiautomatic sectorial analysis. All patients had contrast ventriculography performed during the acute phase and 6 months later. The patients were separated into two groups according to the absence (group I, n = 21) or presence (group II, n = 8) of end-systolic enlargement. The perfusion index in the infarct sectors was -2.29 +/- 2.90 SD in group I and -6.40 +/- 2.85 SD in group II ( P.01). With a cutoff value of -2.46 SD, the sensitivity and specificity of Tc-99m sestamibi SPECT for the prediction of end-systolic volume enlargement were 100% and 62%, respectively. When the functional data from ECG-gated acquisitions were added, specificity increased to 86%.Despite successful PTCA in the acute phase of MI, an increase in end-systolic volume was observed at 6 months in 28% of patients. Tc-99m sestamibi ECG-gated SPECT performed 3 weeks after the acute phase could predict this enlargement with a high accuracy.

In a search for new antineoplastic agents the lead compound N-(4-tert-butylphenyl)-N'-(2-chloroethyl)urea (CEU-22) of a series of 1-aryl-3-(2-chloroethyl)ureas and its iodinated bioisostere CEU-98, were previously selected on the basis of their cytotoxicity and the potent tropism for the intestinal tract (evidenced for CEU-22). In this study, we investigated the antitumour profile of these two drugs for the indication of colon cancer. In vitro, we found that micromolar concentrations of both CEU-22 and CEU-98 inhibited proliferation of DLD-1, Caco-2, HT-29, SW-948 and CT-26 lines. In vivo, a high inhibition of tumour growth and a life span increase were observed when BALB/c mice grafted subcutaneously with CT-26 cells received 5 daily intratumoural injections of each drug. When administered by the intraperitoneal route according to an intermittent schedule starting Day 1 or Day 7 post-implant, only CEU-98 demonstrated antitumour activity ( T / C = 29% for the Day-1,5,9-treatment versus 40% for the Day-7,11,15-treatment) and a life span increase around 40% for the two protocols. These results make CEU-98 a candidate for further investigations with a view to developing an efficacious treatment of colorectal cancer.

Aim : Peroperative detection is usually performed with a gamma probe equipped with a single-hole collimator (SHC). The aim of this study was to compare SHC with a new highly resolutive multi-hole collimator (MHC) in situations simulating the in vivo detection of two radioactive sources. Materials and Methods : The probe was composed of a SHC or a MHC, a CsI(Tl) crystal, a photomultiplier tube and a count rate unit. Sensitivity response curves were experimentally obtained with a 57 Co source. From these values, the response curve in front of two small sources was simulated with an Excel software. A 30 MBq source (A) was placed at 1 cm depth and a 300 kBq source (B) was placed, successively, at 1, 3 and 5 cm. B was then moved towards A by 1 mm steps. A threshold background/signal of 50% was used to determine the minimal distance between the sources ( D min ) to remain separately detectable. Results : At 1, 3 and 5 cm depth, D min was, respectively, 35, 45 and 53 mm for SHC and 14, 17 and 20 mm for MHC and the count rate in front of B was, respectively, 3060, 480 and 210 cps with the SHC and 900, 360 and 150 cps with the MHC. Conclusion : When compared with SHC, the loss in sensitivity with the MHC is only moderate for long source–probe distances while the gain in resolution remains important at any distance. MHC is an interesting option for peroperative detection.

Aim : Radioguided Occult Lesion Localization (ROLL) is a method for guiding the excision of occult breast lesions. A radiotracer is injected preoperatively in the tumor. The surgeon can locate the lesion with a gamma probe. It has been recommended that the tissue is resected where the activity falls rapidly. But this cut-off level can fluctuate depending on the user. The aim of this study was to compare the accuracy of two different types of collimation. Materials and methods : To simulate the detection of a radioactive “lesion”, 0.2 ml of a solution of 99mTc labeled colloids (4 MBq) were deposited at 3 cm depth in a chunk of cow muscle. Detection was performed with a gamma probe (GammaSup, Clerad, F) equipped either with a regular or with an additional high-resolution collimator. The response curve was drawn moving laterally the probe on the chunk of cow by 5 mm steps. Edges of resection were determined with different cut-off levels (from 5 to 50% of maximum counts by 5% steps). Results : Without additional collimator, the mean distance between injection point and resection edge was 18 mm, standard deviation 7.8 mm with a range between 11 and 18 mm. With additional collimator, the mean distance decreased to 10 mm (−44%), standard deviation 4.2 mm (−46%) with a range between 6 and 10 mm. Conclusion : The results demonstrate that the additional collimator provides more precise and reproductive delineation of the injection site. It should be optimal for the ROLL technique.

International audience; The GATE Monte Carlo simulation platform based on the Geant4 toolkit is under constant improvement for dosimetric calculations. In this study, we explore its use for the dosimetry of the preclinical targeted radiotherapy of melanoma using a new specific melanin-targeting radiotracer labeled with iodine 131. Calculated absorbed fractions and S values for spheres and murine models (digital and CT-scan-based mouse phantoms) are compared between GATE and EGSnrc Monte Carlo codes considering monoenergetic electrons and the detailed energy spectrum of iodine 131. The behavior of Geant4 standard and low energy models is also tested. Following the different authors' guidelines concerning the parameterization of electron physics models, this study demonstrates an agreement of 1.2% and 1.5% with EGSnrc, respectively, for the calculation of S values for small spheres and mouse phantoms. S values calculated with GATE are then used to compute the dose distribution in organs of interest using the activity distribution in mouse phantoms. This study gives the dosimetric data required for the translation of the new treatment to the clinic.

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.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.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 (P0.05). 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%, P0.05). The specificity of (18)F-FDG was lower than that of (123)I-BZA2 (54% vs. 86%, P0.05). 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.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.

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.

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.

A rabbit model of osteochondral defects (OD) and spontaneous healing was longitudinally followed over 12 weeks, by in vivo joint scintigraphy using 99mTc-NTP 15-5, and histology. We used two models, one with one OD (OD1 group) in the femoral condyle of one knee and the other with two ODs (OD2 group) in the femoral condyle of one knee, with the contralateral knees serving as the reference. A serial longitudinal imaging study was performed with the scintigraphic ratio (SR, operated knee uptake/contralateral knee uptake) determined at each time-point. ODs were imaged as radioactive defects. The SR was decreased with respective to controls, with values of 0.73 ± 0.08 and 0.65 ± 0.07 in the OD1 and OD2 groups, respectively, at 4 weeks after surgery. Histology of both OD groups revealed the presence of repair tissue characterized by a small amount of sulphated glycosaminoglycans and collagen. 99mTc-NTP 15-5 imaging provided quantitative criteria useful for in vivo evaluation of cartilage trauma and healing.

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

Paillard C, Salmon A, Curtillet C, David A, Halle P, Cachin F, Bordigoni P, Michel G, Rousseau R, Dore E, Isfan F, Merlin E, Rochette E, Demeocq F, Kanold J. Evidence of a clinical response at one yr after reduced-intensity allogeneic hematopoietic stem cell transplantation in heavily pretreated adolescents with aggressive refractory Hodgkin’s lymphoma. Pediatr Transplantation 2010: 14: 109–114. © 2009 John Wiley & Sons A/S. Abstract: We report results of RIC AHSCT in four adolescents with aggressive refractory HL. They all received three or four lines of therapy prior to RIC-AHSCT including autografts. At the time of RIC, they were in partial response except for one patient who had progressive chemoresistant disease. The conditioning regimen consisted of fludarabin, busulfan and ATG. They all had a matched related donor. The median follow-up was 12–16-month post-allograft. All patient transplants engrafted rapidly. The median time of hospitalization was 35 days. The median time to neutrophil recovery (≥500/μL) was 19 days. All the patients were in complete donor chimerism at day 60. Four patients developed skin (grade ≤ II) acute GvHD. All responded and all are alive. Two patients are in CR, one in PR and one relapsed six months after grafting after a PR. Each of the patients in PR received two DLI. These observations, together with the responses after DLI, suggest the presence of a graft vs. lymphoma effect in patients with advanced active HL. Prospective studies are needed to identify the patients likely to benefit most from this treatment approach.

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.