Conception, realization and qualification of a radioactive clean room lab facility dedicated to the synthesis of radiolabeled API for human ADME studies.

The human absorption, distribution, metabolism and elimination study administering radiolabeled drugs to human volunteers is an important clinical study in the development program of new drug candidates. The manufacture of radiolabeled Active Pharmaceutical Ingredients is covered by national drug laws and may come within the scope of regulatory GMP requirements. Additionally, authorities may request an appropriate environmental zoning to minimize the risk of microbiological contaminations particularly during the synthesis of radiolabeled Active Pharmaceutical Ingredients intended for parenteral application. Thus, a radioactive clean room lab facility in line with both GMP and radiation safety regulations was installed and the environmental zoning validated by appropriate testing of technical parameters and microbial and particle monitoring. The considerations detailed in this paper cover only GMP aspects related to the synthesis of radioactive drug substance. The subsequent, final formulation step in the overall process for manufacturing of radioactive drug product for any kind of administration is not within the scope of this paper. Under these qualified and controlled environmental conditions, we are now in a position to provide radiolabeled drug substances for all kinds of drug administration including both po and iv.

Triantennary GalNAc Molecular Imaging Probes for Monitoring Hepatocyte Function in a Rat Model of Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease that can lead to irreversible liver cirrhosis and cancer. Early diagnosis of NASH is vital to detect disease before it becomes life-threatening, yet noninvasively differentiating NASH from simple steatosis is challenging. Herein, bifunctional probes have been developed that target the hepatocyte-specific asialoglycoprotein receptor (ASGPR), the expression of which decreases during NASH progression. The results show that the probes allow longitudinal, noninvasive monitoring of ASGPR levels by positron emission tomography in the newly developed rat model of NASH. The probes open new possibilities for research into early diagnosis of NASH and development of drugs to slow or reverse its progression.