The Development of <sup>18</sup>F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1
Hsiaoju Lee, Sally W. Schwarz, Erin K. Schubert, Delphine L. Chen, Robert K. Doot, Mehran Makvandi, Lilie L. Lin, Elizabeth S. McDonald, David A. Mankoff, Robert H. Mach
Abstract
Fluorine 18 (18F) fluorthanatrace (18F-FTT) is a PET radiotracer for imaging poly (adenosine diphosphate–ribose) polymerase-1 (PARP-1), an important target for a class of drugs known as PARP inhibitors, or PARPi. This article describes the stepwise development of this radiotracer from its design and preclinical evaluation to the first-in-human imaging studies and the initial validation of 18F-FTT as an imaging-based biomarker for measuring PARP-1 expression levels in patients with breast and ovarian cancer. A detailed discussion on the preparation and submission of an exploratory investigational new drug application to the Food and Drug Administration is also provided. Additionally, this review highlights the need and future plans for identifying a commercialization strategy to overcome the major financial barriers that exist when conducting the multicenter clinical trials needed for approval in the new drug application process. The goal of this article is to provide a road map that scientists and clinicians can follow for the successful clinical translation of a PET radiotracer developed in an academic setting. Keywords: Molecular Imaging-Cancer, PET, Breast, Genital/Reproductive, Chemistry, Radiotracer Development, PARPi, 18F-FTT, Investigational New Drug © RSNA, 2022