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

Area of Science:

• Oncology
• Nuclear Medicine
• Molecular Imaging

Background:

• Poly(ADP-ribose) polymerase (PARP) inhibitors are effective cancer treatments for tumors with DNA damage response defects.
• Identifying patients who will benefit from PARP inhibitors requires improved methods.
• Noninvasive assessment of PARP activity is crucial for treatment selection.

Purpose of the Study:

• To evaluate 18F-FluorThanatrace (18F-FTT) PET/CT for noninvasive assessment of PARP activity.
• To determine associations between 18F-FTT uptake, tumor mutational status, and prior therapies.

Main Methods:

• Whole-body 18F-FTT PET/CT scans were performed on 52 solid tumor patients before PARP inhibitor treatment.
• Maximum standardized uptake values (SUVmax) were recorded for up to five lesions per patient.
• Lesion-specific analysis included tumor type, mutation status, and prior treatment history.

Main Results:

• 18F-FTT uptake was observed in all patients, with significant variations by primary tumor type.
• Lesions with BRCA2 mutations showed higher 18F-FTT uptake compared to other mutations (6.7 vs. 5.5).
• Prior PARP inhibitor or systemic therapy was associated with lower 18F-FTT SUVmax.

Conclusions:

• 18F-FTT PET/CT offers a noninvasive method for quantifying PARP1 enzyme activity in solid tumors.
• 18F-FTT uptake is influenced by tumor mutational status and prior treatment history.
• This tracer may aid in selecting patients for PARP inhibitor therapy.