Abstract
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, in vitro and in vivo 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.
Highlights
New radiopharmaceuticals intended for clinical use typically follow complex drug-development sequences that expend considerable resources and time
While additional research is needed, the demonstration that a radiopharmaceutical is specific, selective, and deliverable against tumors in a patient subgroup likely to benefit from its administration remains essential in the critical evaluation of oncology therapeutic radiopharmaceuticals intended for clinical use
We argue that a conventional microdose study informs the evaluation of oncology therapeutic radiopharmaceuticals by providing more data on human i) biological effects, ii) starting doses, and iii) schedules
Summary
Kunos 1*, Rodney Howells 1, Aman Chauhan 2, Zin W. Bernard 3, Riham El Khouli 4 and Jacek Capala 5. Specialty section: This article was submitted to Radiation Oncology, a section of the journal
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