PURPOSE

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

METHODS

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

RESULTS

Precursors that did not lose binding affinity for PARP were designed, synthesized, and then labelled with Ga in high radiochemical purity (> 97%). The Ga-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 Ga-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 Ga-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.

CONCLUSION

As the first Ga-labelled PARP inhibitor, Ga-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.