Abstract:
Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with
inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand
deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA
damage, forming a non-functional “PARP enzyme–inhibitor complex” leading to cell cytotoxicity.
The effect is more pronounced in the presence of PARP upregulation and homologous recombination
(HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies
by genomic analysis—for instance, BRCA1/2 used in triple-negative breast cancer—should be a part of
the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations
do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors
beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in
PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing
factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive,
and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor
pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review,
we discuss [18F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP
expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible
causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a
tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.
