188Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside

Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (Eβmax = 2.1 MeV) for the treatment of HCC. The major “milestones” of this development, from the first syntheses to the recent first injection in man, are described

Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization

International audiencePURPOSE: Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. METHODS: Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. RESULTS: Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. CONCLUSION: SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind

EVALUATION DE NOUVEAUX RADIOPHARMACEUTIQUES<br />Synthèse, évaluation, et biodistribution de nouveaux radioligands peptidiques de VCAM-1 et avb3

The development of nuclear medicine implies the search for new isotopes but also for new vectors specific of functions or metabolic pathways. We investigated new radiopharmaceuticals intended for new diagnostic approaches of two physiopathological mechanisms frequently met in our populations: the atherosclerosis vulnerable plaque and the tumor angiogenesis. We studied and optimized the iodine and 99m-technetium radiolabelling, of a series of peptides in order to allow the in vivo use of these tracers for imaging studies in animals and possibly in humans. The radioiodination was carried out by electrophilic substitution, and technetium was linked by a tricarbonyle BFCA (IsoLink). The reaction parameters were defined so that the labelling reaction presents a high radiochemical purity (>95%), and a high specific activity. The reactions are fast and reproducible. Various physicochemical properties: liposolubility, stability of labelling, and pharmacokinetic properties: nonspecific binding, metabolization and organ biodistribution of peptides in animal model, were studied. These results indicate which peptide may be a suitable candidate for targeting trials.Le développement de la médecine nucléaire passe par la recherche de nouveaux isotopes mais aussi de nouveaux vecteurs spécifiques de fonctions ou de voies métaboliques. L'équipe INSERM E0340 développe de nouveaux radiotraceurs destinés à de nouvelles approches diagnostiques de deux mécanismes physio-pathologiques fréquemment rencontrés dans nos populations : la plaque d'athérome vulnérable et la néoangiogenèse tumorale. Nous avons mis au point et optimisé le radiomarquage, à l'iode et au technétium 99m, d'une série de peptides afin de permettre l'utilisation de ces traceurs pour des études d'imagerie in vivo chez l'animal puis chez l'homme. La radioiodation a été effectuée par substitution électrophile, et le technétium a été fixé par l'intermédiaire d'un petit synthon tricarbonyle (IsoLink). Les paramètres de réaction ont été définis afin que la réaction de marquage présente un haut rendement de marquage, et une forte activité spécifique. Les réactions sont rapides et reproductibles et la mise en forme compatible avec une utilisation in vivo. Les différentes propriétés physico-chimiques : liposolubilité, stabilité du marquage, et les propriétés pharmacocinétiques : pourcentage de liaison non spécifique, métabolisation, biodistribution des peptides, ont été mesurés. Les études ont permis de sélectionner le radioligand présentant les meilleurs critères pour une utilisation in vivo en imagerie

Therapy of hepatocellular carcinoma with Rhenium-188 Lipiodol

International audienc

Composition for therapeutic use, including an organic lipid phase and a rare- earth radioisotope complex

The invention relates to a therapeutic compn. including a complex having the following formula (1)​, including a rare-​earth radioisotope in ionic form, said complex being solubilized in an org. lipophilic phase: [M(L)​3] in which: M denotes the rare-​earth radioisotope in ionic form, and L denotes a tropolone ligand or a ligand derived from tropolone

Reduction of β-radiation exposure during preparation of 188Re-labelled Lipiodol for hepatocellular carcinoma treatment.

International audienceRhenium-188 (188Re) is of widespread interest for treating various diseases because of its attractive physical and chemical properties. The routine preparation of therapeutic doses of 188Re-labelled tracers can result in significant radiation exposure to the operator. We studied the impact of automating the preparation of 188Re-Lipiodol on the radiochemist's exposure, as well as the importance of the model of syringe shielding. To monitor radiation exposure continuously readable electronic personal dosimeters were used. Thermoluminescence dosimeters were fixed to the probable most exposed fingers of the radiochemist during preparation of the radiotracer and during the syringing. Dose rates were measured using a Babyline. Automation of the synthesis reduced personal dose equivalents from 2.60±4.35 to 1.61±1.20 µSv/GBq [Hp(10)] and from 38.37±55.28 to 21.84±16.14 µSv/GBq [Hp(0.07)]. Dose to the extremities was also reduced (-80% for the right hand; -58% for the left one). The Lemer-Pax PSWG syringe shield led to a slightly lower dose to the hands compared with the Medisystem (1.1±0.27 vs. 1.34±0.6 mSv/GBq for the right finger). Automation of the synthesis leads to a significant decrease in radiation exposure to the operator. The Lemer-Pax PSWG syringe shield provides better hand protection than the smaller Medisystem Mediclic

Optimization of hepatocarcinoma uptake with radiolabeled lipiodol: development of new lipiodol formulations with increased viscosity.

International audienceThe aim of this study was to develop new Lipiodol formulations with increased viscosities to augment Lipiodol embolic effect and optimize efficiency of radiolabeled Lipiodol in hepatocarcinoma treatments. New Lipiodol formulations consist of Lipiodol mixtures with different stearic acid concentrations (0.8%, 1.3%, and 1.8%). These formulations were fully characterized in vitro (viscosity, rheologic profiles) and labeled with 99mTc. Their viscosities at 20°C are 54, 60, and 67cP respectively, versus 45cP for Lipiodol ultra-fluide. Second, their biodistribution profiles were studied in vivo, at 24 and 72 hours, in hepatoma-bearing rats, and compared to control group (99mTc-Lipiodol). Biodistribution at 24 hours show a Gaussian tumor uptake profile with a maximum obtained with 1.3% stearic acid, and a tumor uptake superior to control group (+67%) (p<0.05). At 72 hours, optimal tumor uptake is reached with the 0.8% formulation, with 89% increase compared with control group (p<0.05). Moreover, we show a tendency to the decrease of pulmonary uptake for the new formulations at 24 hours and 72 hours. These results suggest a correlation between viscosity and Lipiodol tumor uptake. The new 0.8% stearic acid/Lipiodol formulation appears to be the optimized formulation for Lipiodol treatments of hepatocarcinoma, since it leads to a significant increase of tumor uptake at 72 hours and possibly to a decrease of undesirable pulmonary effects

Automation of labelling of Lipiodol with high-activity generator-produced 188Re.

International audienceThis work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52±2.3% and extraction yield was 98.56±1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68±9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ((188)Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07±0.9%)