Marie-Dominique Desruet

Periaortic Brown Adipose Tissue as a Major Determinant of [18F]-Fluorodeoxyglucose Vascular Uptake in Atherosclerosis-Prone, ApoE−/− Mice

Background [18F]-fluorodeoxyglucose (FDG) has been suggested for the clinical and experimental imaging of inflammatory atherosclerotic lesions. Significant FDG uptake in brown adipose tissue (BAT) has been observed both in humans and mice. The objective of the present study was to investigate the influence of periaortic BAT on apolipoprotein E-deficient (apoE−/−) mouse atherosclerotic lesion imaging with FDG. Methods ApoE−/− mice (36±2 weeks-old) were injected with FDG (12±2 MBq). Control animals (Group A, n = 7) were injected conscious and kept awake at room temperature (24°C) throughout the accumulation period. In order to minimize tracer activity in periaortic BAT, Group B (n = 7) and C (n = 6) animals were injected under anaesthesia at 37°C and Group C animals were additionally pre-treated with propranolol. PET/CT acquisitions were performed prior to animal euthanasia and ex vivo analysis of FDG biodistribution. Results Autoradiographic imaging indicated higher FDG uptake in atherosclerotic lesions than in the normal aortic wall (all groups, P<0.05) and the blood (all groups, P<0.01) which correlated with macrophage infiltration (R = 0.47; P<0.001). However, periaortic BAT uptake was either significantly higher (Group A, P<0.05) or similar (Group B and C, P = NS) to that observed in atherosclerotic lesions and was shown to correlate with in vivo quantified aortic FDG activity. Conclusion Periaortic BAT FDG uptake was identified as a confounding factor while using FDG for the non-invasive imaging of mouse atherosclerotic lesions.

Optimal treatment of painful bone metastases with Samarium EDTMP in a haemodialysis patient: effectiveness and safety of internal radiotherapy

One of the current therapeutic approaches in the treatment of osteoblastic bone metastases uses the affinity of Samarium ((153)Sm) ethylene-diamine-tetramethylene phosphonic acid (EDTMP) for bone areas of bone turnover. As Samarium EDTMP is a beta-emitter, the radiotherapy contributes to osteoblastic bone lesion control over time. To date, the safety and effectiveness of Samarium therapy have not been established in patients with renal impairment. In this first report, we describe our experience of use of Samarium EDTMP in conjunction with biphosphonates in a haemodialysis patient for treatment of painful bone metastasis. Encouraging results were obtained in achieving pain control. The use of this radioisotope could be more widely applied to treat haemodialysis patients.

Selective mono-radioiodination and characterization of a Cell-Penetrating Peptide: L-Tyr-Maurocalcine

Abstract Mono-and poly- iodinated peptides form frequently during radioiodination procedures. However, the formation of a single species in its mono-iodinated form is essential for quantitative studies such as determination of tissue concentration or image quantification. Therefore, the aim of the present study was to define the optimal experimental conditions in order to exclusively obtain the mono-iodinated form of L-maurocalcine (L-MCa). L-MCa is an animal venom toxin which was shown to act as a cell-penetrating peptide. In order to apply the current direct radioiodination technique using oxidative agents including chloramine T, Iodo-Gen® or lactoperoxidase, an analogue of this peptide containing a tyrosine residue (Tyr-L-MCa) was synthesized and was shown to fold/oxidize properly. The enzymatic approach using lactoperoxidase/H2O2 was found to be the best method for radioiodination of Tyr-L-MCa. MALDI-TOF mass spectrometry analyses were then used for identification of the chromatographic eluting components of the reaction mixtures. We observed that the production of different radioiodinated species depended upon the reaction conditions. Our results successfully described the experimental conditions of peptide radioiodination allowing the exclusive production of the mono-iodinated form with high radiochemical purity and without the need for a purification step. Mono-radioiodination of L-Tyr-MCa will be crucial for future quantitative studies, investigating the mechanism of cell penetration and in vivo biodistribution.

Evaluation of a human anti-mouse antibody rapid test for patients requiring radio-immunodiagnostic

Monoclonal antibodies (mAbs) play a significant part in the diagnostic and therapeutic arsenal. They are used in many fields of medicine, ranging from in vitro diagnosis to the treatment of multiple pathologies in such diverse areas as infectious diseases, immunology and oncology. The first mention of the use of radiolabeled antibodies dates from the 1950s. However, from the first tests, several problems with the use of radiolabeled antibodies appeared. One of these involved the use itself of the antibodies because they caused an immune response and the production of human anti-mouse antibodies (HAMAs) [1]. Complications related to this immunization are very rare and have a high inter-individual variability [2–4]. It is widely accepted that the presence of these heterophilic antibodies could influence the effectiveness of the immunotherapy and immunoscintigraphy, and could also be considered as responsible for analytical interference in immunoassays [5, 6]. Indeed, HAMAs bind to the newly administered mAbs, leading to the formation of immune complexes (HAMA-mAb) that may decrease the therapeutic efficacy and diagnostic value of the new mAb conjugates. Similarly, allergic reactions could occur, motivating the search for HAMAs before any reintroduction of mAbs [7]. Current tests for HAMA detection do not allow one to quickly obtain the status of patients. To develop a simple, rapid and reliable test for monitoring the presence of HAMA in some patients, Milenia GmbH (Hamburg, Germany) has recently proposed a new qualitative test based on the principle of a rapid lateral flow test on a strip. We proposed to evaluate this Quicktest on our cohort of patients who had tested positive for HAMAs using the quantitative Medac HAMA-ELISA test. Serum samples from patients positive for HAMA were obtained from a serum bank collected between 1992 and 1999 in the Nuclear Medicine Department of Grenoble University Hospital. The patients had received radioimmunotherapy and subsequently developed HAMAs demonstrated using the quantitative Medac test. Sera were estimated again in 2014 using the same test to verify the persistence of expression of HAMA. This test is a one-step enzyme immunoassay for the quantitative determination of HAMA in serum realized in 1 h. The test is calibrated against anti-mouse IgG antibodies. The measuring range is from 40 to 2000 ng/mL. Samples and peroxidase-labeled mouse IgG conjugate are added together to the plate that is pre-coated with mouse IgG (antigen). The HAMAs bind to the solid phase and to peroxidase-labeled mouse IgG. Then, there is an incubation step with a tetra-methyl benzidine substrate. The reaction is stopped by the addition of sulfuric acid, and the absorption is read photometrically at 450 nm. According to the manufacturer, the limit *Corresponding author: Marie-Dominique Desruet, PhD, PharmD, Radiopharmacy/ Nuclear Medicine Department, Grenoble University Hospital, CS 10217 38043 GRENOBLE cedex 9, France, Phone: + (0)33 476 769 410, Fax: + (0)33 476 767 108, E-mail: mddesruet@chu-grenoble.fr; and Pharmacy Department, Grenoble University Hospital, Grenoble, France Chloé Lamesa: Pharmacy Department, Grenoble University Hospital, Grenoble, France; and UMR-S INSERM 1039 Bioclinical Radiopharmaceutical Unit, Grenoble, France Anne-Sophie Gauchez: UMR-S INSERM 1039 Bioclinical Radiopharmaceutical Unit, Grenoble, France; and Radioactivity Platform, Biology Department, Grenoble University Hospital, Grenoble, France Roseline Mazet and Luc Foroni: Pharmacy Department, Grenoble University Hospital, Grenoble, France Daniel Fagret: UMR-S INSERM 1039 Bioclinical Radiopharmaceutical Unit, Grenoble, France; and Nuclear Medicine Unit, Imaging Department, Grenoble University Hospital, Grenoble, France