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

2021; Springer Science+Business Media; Volume: 49; Issue: 3 Linguagem: Inglês

10.1007/s00259-021-05436-7

1619-7089

Sophie Stotz, Johannes Kinzler, Anne T. Nies, Matthias Schwab, Andreas Maurer,

Advanced Electron Microscopy Techniques and Applications

Abstract Purpose Imaging of PARP expression has emerged as valuable strategy for prediction of tumor malignancy. While [ 18 F]PARPi and [ 18 F]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 [ 18 F]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 [ 18 F]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 [ 18 F]PARPi, [ 18 F]FPyPARP, and [ 18 F]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 [ 18 F]PARPi, [ 18 F]FPyPARP, and [ 18 F]FTT), a partial shift from hepatobiliary to renal clearance of [ 18 F]FPyPARP was observed, whereas [ 18 F]PARPi and [ 18 F]FTT show almost exclusive hepatobiliary clearance. Conclusion These findings imply that [ 18 F]FPyPARP is an alternative to [ 18 F]PARPi and [ 18 F]FTT for PET imaging of PARP enzymes.