PET imaging of PARP expression using ⁶⁸Ga-labelled inhibitors

Imaging the PARP expression using ¹⁸F probes has been approved in clinical trials. Nevertheless, hepatobiliary clearance of both ¹⁸F probes hindered their application in monitoring abdominal lesions. Our novel ⁶⁸Ga-labelled probes aim for fewer abdominal signals while ensuring PARP targeting by optimizing the pharmacokinetic properties of radioactive probes.

Three radioactive probes targeted PARP were designed, synthesized, and evaluated based on the PARP inhibitor Olaparib. These ⁶⁸Ga-labelled radiotracers were assessed in vitro and in vivo.

Precursors that did not lose binding affinity for PARP were designed, synthesized, and then labelled with ⁶⁸Ga in high radiochemical purity (> 97%). The ⁶⁸Ga-labelled radiotracers were stable. Due to the increased expression of PARP-1 in SK-OV-3 cells, the uptake of the three radiotracers by SK-OV-3 cells was significantly greater than that by A549 cells. PET/CT imaging of the SK-OV-3 models indicated that the tumor uptake of ⁶⁸Ga-DOTA-Olaparib (0.5 h: 2.83 ± 0.55%ID/g; 1 h: 2.37 ± 0.64%ID/g) was significantly higher than that of the other ⁶⁸Ga-labelled radiotracers. There was a significant difference in the T/M (tumor-to-muscle) ratios between the unblocked and blocked groups as calculated from the PET/CT images (4.07 ± 1.01 vs. 1.79 ± 0.45, P = 0.0238 < 0.05). Tumor autoradiography revealed high accumulation in tumor tissues, further confirming the above data. PARP-1 expression in the tumor was confirmed by immunochemistry.

As the first ⁶⁸Ga-labelled PARP inhibitor, ⁶⁸Ga-DOTA-Olaparib displayed high stability and quick PARP imaging in a tumor model. This compound is thus a promising imaging agent that can be used in a personalized PARP inhibitor treatment regimen.