AUTHOR=Kunos Charles A. , Howells Rodney , Chauhan Aman , Myint Zin W. , Bernard Mark E. , El Khouli Riham , Capala Jacek 

TITLE=Radiopharmaceutical Validation for Clinical Use

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.630827

DOI=10.3389/fonc.2021.630827

ISSN=2234-943X

ABSTRACT=<p>Radiopharmaceuticals are reemerging as attractive anticancer agents, but there are no universally adopted guidelines or standardized procedures for evaluating agent validity before early-phase trial implementation. To validate a radiopharmaceutical, it is desirous for the radiopharmaceutical to be specific, selective, and deliverable against tumors of a given, molecularly defined cancer for which it is intended to treat. In this article, we discuss four levels of evidence—target antigen immunohistochemistry, <italic>in vitro</italic> and <italic>in vivo</italic> preclinical experiments, animal biodistribution and dosimetry studies, and first-in-human microdose biodistribution studies—that might be used to justify oncology therapeutic radiopharmaceuticals in a drug-development sequence involving early-phase trials. We discuss common practices for validating radiopharmaceuticals for clinical use, everyday pitfalls, and commonplace operationalizing steps for radiopharmaceutical early-phase trials. We anticipate in the near-term that radiopharmaceutical trials will become a larger proportion of the National Cancer Institute Cancer Therapy Evaluation Program (CTEP) portfolio.</p>