Occupational internal monitoring in nuclear medicine service of Sainte-Anne military hospital: previous considerations and results.

The Nuclear Medicine Department of Sainte-Anne military hospital in Toulon uses 99mTc, 123I and 18F unsealed sources to provide therapeutic and diagnostic care. For a few years, only ambient air and surface monitoring were performed to check the absence of internal contamination risk for workers. To verify this risk assessment hypothesis, confirmatory monitoring programme including in vivo and in vitro measurements was performed by the French defence radiation protection service (SPRA, Clamart). Here, due to the short half-life of targeted radionuclides, the analytical sensitivity was determined with estimations of minimal detectable activities and derived recording levels. It was shown that sensitivity was sufficient to detect an internal contamination leading to an effective dose of 0.1 mSv for few days post intake. At the same time, around 20 whole-body countings were performed. Results were below minimal detectable activity and were confirmed by 24-hours urine analysis. So, actual working conditions do not lead to measurable internal contamination for nuclear medicine staff.

MBL-II-141, a chromone derivative, enhances irinotecan (CPT-11) anticancer efficiency in ABCG2-positive xenografts.

ABCG2 is responsible for the multidrug resistance (MDR) phenotype, and strongly modulates cancer outcomes. Its high expression at a number of physiological barriers, including blood-brain and intestinal barriers, impacts on drug pharmacokinetics parameters. We characterized MBL-II-141, a specific and potent ABCG2 inhibitor. Combination of 10 mg/kg MBL-II-141 with the anticancer agent CPT-11 completely blocked the growth of 90% freshly implanted ABCG2-positive tumors. Moreover, the same combination slowed the growth of already established tumors. As required for preclinical development, we defined the main pharmacokinetics parameters of MBL-II-141 and its influence on the kinetics of CPT-11 and its active metabolite SN-38 in mice. MBL-II-141 distribution into the brain occurred at a low, but detectable, level. Interestingly, preliminary data suggested that MBL-II-141 is well tolerated (at 50 mg/kg) and absorbed upon force-feeding. MBL-II-141 induced a potent sensitization of ABCG2-positive xenografts to CPT-11 through in vivo ABCG2 inhibition. MBL-II-141 strongly increased CPT-11 levels in the brain, and therefore would be a valuable agent to improve drug distribution into the brain to efficiently treat aggressive gliomas. Safety and other pharmacological data strongly support the reglementary preclinical development of MBL-II-141.