Two experts and a newbie: [18F]PARPi vs [18F]FTT vs [18F]FPyPARP-a comparison of PARP imaging agents

Purpose Imaging of PARP expression has emerged as valuable strategy for prediction of tumor malignancy. While [F-18]PARPi and [F-18]FTT are already in clinical translation, both suffer from mainly hepatobiliary clearance hampering their use for detection of abdominal lesions, e.g., liver metastases. Our novel radiotracer [F-18]FPyPARP aims to bridge this gap with a higher renal clearance and an easily translatable synthesis route for potential clinical application. Methods We developed a less lipophilic variant of [F-18]PARPi by exchange of the fluorobenzoyl residue with a fluoronicotinoyl group and automated the radiosyntheses of the three radiotracers. We then conducted a comparative side-by-side study of [F-18]PARPi, [F-18]FPyPARP, and [F-18]FTT in NOD.CB17-Prkdc(scid)/J mice bearing HCC1937 xenografts to assess xenograft uptake and pharmacokinetics focusing on excretion pathways. Results Together with decent uptake of all three radiotracers in the xenografts (tumor-to-blood ratios 3.41 +/- 0.83, 3.99 +/- 0.99, and 2.46 +/- 0.35, respectively, for [F-18]PARPi, [F-18]FPyPARP, and [F-18]FTT), a partial shift from hepatobiliary to renal clearance of [F-18]FPyPARP was observed, whereas [F-18]PARPi and [F-18]FTT show almost exclusive hepatobiliary clearance. Conclusion These findings imply that [F-18]FPyPARP is an alternative to [F-18]PARPi and [F-18]FTT for PET imaging of PARP enzymes.

Automated summary

The study introduced a novel radiotracer [F-18]FPyPARP with higher renal clearance and an easily translatable synthesis route for potential clinical application, aiming to address the issue of hepatobiliary clearance in [F-18]PARPi and [F-18]FTT for abdominal lesion detection. Comparative study in mice showed [F-18]FPyPARP had a partial shift from hepatobiliary to renal clearance, making it a potential alternative for PET imaging of PARP enzymes compared to [F-18]PARPi and [F-18]FTT.