Conséquences fonctionnelles de la simulation des récepteurs du Neuropeptide FF (étude par imagerie cérébrale au [14C]2-déoxyglucose chez la souris)

Neuropeptide FF (NPFF) is a neuromediator modulating opioid system activity. To determine brain regions involved in pharmacological activities of NPFF, particularly in interaction with opioid system, cerebral activity modifications induced by NPFF analogues were studied in absence or presence of morphine.NPFF receptors stimulation induces cerebral activity decrease, in regions involved in nociception and motor activity control. These effects are inhibited by morphine, suggesting that NPFF system is modulated by opioid system. Comparison of cerebral activity modifications induced by NPFF analogues with different selectivity suggests that NPFF2 receptors are involved in audition and NPFF1 receptors in functions associated with the limbic system.TOULOUSE3-BU Santé-Centrale (315552105) / SudocTOULOUSE3-BU Santé-Allées (315552109) / SudocSudocFranceF

Zirconium 89 and Copper 64 for ImmunoPET: From Antibody Bioconjugation and Radiolabeling to Molecular Imaging

Immunotherapy has transformed cancer treatment. Nevertheless, given the heterogeneity of clinical efficacy, the multiplicity of treatment options available and the possibility of serious adverse effects, selecting the most effective treatment has become the greatest challenge. Molecular imaging offers an attractive way for this purpose. ImmunoPET provides specific imaging with positron emission tomography (PET) using monoclonal antibodies (mAb) or its fragments as vector. By combining the high targeting specificity of mAb and the sensitivity of PET technique, immunoPET could noninvasively and dynamically reveal tumor antigens expression and provide theranostic tools of several types of malignancies. Because of their slow kinetics, mAbs require radioelements defined by a consistent half-life. Zirconium 89 (89Zr) and Copper 64 (64Cu) are radiometals with half-lives suitable for mAb labeling. Radiolabeling with a radiometal requires the prior use of a bifunctional chelate agent (BFCA) to functionalize mAb for radiometal chelation, in a second step. There are a number of BFCA available and much research is focused on antibody functionalization techniques or on developing the optimum chelating agent depending the selected radiometal. In this manuscript, we present a critical account of radiochemical techniques with radionuclides 89Zr and 64Cu and their applications in preclinical and clinical immuno-PET imaging

Hypoxie tumorale (place de l'Imagerie Fonctionnelle au 18FMISO)

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Place de la radio-immunothérapie au 90y-zevalin® dans le traitement des lymphomes non-hodgkiniens (expérience du CHU de Limoges)

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Radiomarquage des immunoglobulines A et G au technetium 99M et étude in vitro

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Les polymères à empreintes moléculaires (théorie et application à un médicament radiopharmaceutique)

LYON1-BU Santé (693882101) / SudocLIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Pharmacologie intégrée et activité cérébrale des récepteurs NPFF1 et NPFF2

TOULOUSE3-BU Sciences (315552104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig) appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc), an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT). Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%). 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C) and in serum (37°C), even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe" and preserves Ig affinity for antigen, as shown by both in vitro and in vivo experiments. This method could easily be used with noncommercial IgG or other antibody isotypes

Adverse Reactions to Radiopharmaceuticals in France

Background: Radiopharmaceuticals are regarded as safe by the nuclear medicine community, but up to now, no survey has been conducted with from the perspective of pharmacovigilance. Objective: To describe the adverse reactions to radiopharmaceuticals (ARRPs) reported to the French Pharmacovigilance Database (FPVD). Methods: We selected and described all reports encompassing at least one radiopharmaceutical in the FPVD. The annual incidence of reported ARRPs used in diagnosis was also estimated. Results: From 1989 to 2013, 304 reports of ARRPs were identified (43.0% serious, 12 deaths) in 54.6% women and 45.4% men; the median age was 58 years. Five therapeutic radiopharmaceuticals (131I-sodium iodide, 131I-lipiodol, 89Sr-chloride, 153Sm-lexidronam, and 90Y-ibritumomab-tiuxetan) were involved in 48 reports (97 adverse reactions: 86.6% serious, 9 deaths). Pulmonary disorders represented 44.3% of ARRPs used for therapy, mainly related to 131I-lipiodol. There were 34 diagnostic radiopharmaceuticals involved in 256 reports (451 adverse reactions: 38.1% serious, 3 deaths); 8 diagnostic products (99mTc-oxidronate, 18F-fluorodeoxyglucose, 99mTc-tin pyrophosphate, 99mTc-tetrofosmin, 99mTc-dimercaptosuccinic acid, 201Tl-chloride, 99mTc-sestamibi, and 111In-pentetate) accounted for two-thirds of ARRPs. The most frequent adverse reactions were skin (34.4%), general (18.2%), nervous (9.0%), and gastrointestinal disorders (7.0%). There were 25 cases of altered images and 10 medication errors. The annual incidence of reported adverse reactions ranged from 1.2 × 10−5 to 3.4 × 10−5 diagnostic administrations. Conclusions: Reported ARRPs occurred rarely and were more serious in the therapeutic than in the diagnostic field. The notification of ARRPs was able to provide new guidance for safe use, as was the case for 131I-lipiodol. Therefore, it is important to report ARRPs to a pharmacovigilance system. </jats:p