# Baseline PARP-1 PET imaging in patients with advanced solid tumors with DNA damage response mutations

## TL;DR

This study shows that a new PET imaging technique can noninvasively measure PARP activity in tumors, with higher uptake in BRCA2-mutated tumors and lower uptake in those previously treated with PARP inhibitors.

## Contribution

The study introduces and validates [18F]-FTT PET/CT as a novel noninvasive method to assess PARP1 activity in tumors with DNA damage response mutations.

## Key findings

- Higher [18F]-FTT uptake was observed in lesions with BRCA2 mutations compared to other mutations.
- Prior PARP inhibitor therapy was associated with significantly lower SUVmax values in [18F]-FTT PET/CT scans.
- Uptake varied significantly by primary tumor type, suggesting potential for tumor-specific imaging applications.

## Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before beginning PARP inhibitor treatment. The maximum standardized uptake value (SUVmax) was recorded for up to five lesions per patient. All recorded lesions were included in the analysis.

Uptake of [18F]-FTT was confirmed in all 52 patients regardless of primary tumor type (20 breast, 12 ovarian, 7 prostate, 3 pancreas, and 10 other). Lesion-by-lesion analysis revealed significant differences in [18F]-FTT uptake by primary tumor type (P < 0.001) and higher uptake in lesions with BRCA2 mutations (n = 65) than in lesions with other genetic mutations (n = 26) (6.7 vs. 5.5, P = 0.03). Prior receipt of PARP inhibitor was associated with lower SUVmax (4.7 vs. 6.4, P = 0.001), and prior receipt of systemic therapy was also associated with lower SUVmax (4.0 vs. 6.0, P = 0.01).

[18F]-FTT PET/CT may be useful as a noninvasive quantitative assessment of PARP1 enzyme activity in patients with solid tumors; uptake of [18F]-FTT varies based on tumor mutational status and receipt of prior PARP inhihbitor therapy and/or systemic therapy.