Preclinical and first-in-human-brain-cancer applications of [18F]poly-(ADP-ribose) polymerase inhibitor PET/MR.

We report pre-clinical and first-in-human-brain-cancer data using a targeted poly(ADP-ribose)polymerase1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment related changes. In a pre-clinical mouse model, we illustrated that [18F]PARPi crosses the blood-brain barrier and specifically binds to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment related changes, independent of blood brain-barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancers than non-cancers. Specificity was also corroborated by blocking fluorescent tracer uptake with excess of unlabeled PARP inhibitor in fresh cancer tissue derived from a patient. Although larger studies are necessary to confirm and further explore this tracer, we describe an encouraging role for the use of [18F]PARPi as a diagnostic tool in evaluating patients with brain cancers and possible treatment related changes.