Optimizing the performance of ⁶⁸Ga labeled FSHR ligand in prostate cancer model by co-administration of aprotinin

Abstract

Purpose

Radiolabeled FSH1 peptides are potential specific probes for FSHR imaging. However, moderate uptakes and fast washout from the tumors may limit its widespread use. In this study, ⁶⁸Ga labeled modified FSH1 analogs was prepared and the imaging properties were determined in the prostate cancer model with or without aprotinin.

Methods

NOTA-MAL-FSH4 was synthesized and labeled with ⁶⁸Ga. The pharmacokinetic profile of the peptide after co-administration with aprotinin was determined through metabolism analyses and microPET imaging.

Results

⁶⁸Ga-NOTA-MAL-FSH4 was successfully prepared. The IC50 value of displacement ⁶⁸Ga-NOTA-MAL-FSH4 with FSH1 was 139.4 ± 1.16 nM. The PC-3 prostate tumor was visible after administration of the ⁶⁸Ga labeled tracer. In vitro RP-HPLC analysis revealed that the average percentage of intact peptide in the plasma, liver and tumor was 8.30, 9.57 and 7.06% respectively. In presence of aprotinin, the amounts of intact peptide increased to 34.32%, 20.63% and 15.39% in the counterparts respectively. MicroPET imaging showed that the uptakes of PC-3 tumors at 60mins after co-administration of 100 μg, 200 μg or 400 μg enzyme inhibitors were 2.91 ± 0.21%ID/g, 3.89 ± 0.16%ID/g and 9.21 ± 0.22%ID/g respectively.

Conclusion

With the aid of a serine protease inhibitor, the performance of the ⁶⁸Ga labeled peptide was optimized, which may benefit further clinical application.

Keywords:

• FSHR
• cancer
• PET
• 68Ga
• aprotinin

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was partially supported by National Natural Science Foundation [22075114, 31971316], Jiangsu Provincial Natural Science Foundation [BK20192005, BRA2019105], Jiangsu talent projects [LGY2017088, WSN-082], Jiangsu Provincial Commission of Health and Family Planning Foundation [QNRC2016628] and Wuxi Science Foundation [N20192014].

Notes on contributors

Donghui Pan

Donghui Pan, PhD, Associate professor. He is experienced in the synthesis of radiolabeled compounds.

Lizhen Wang

Lizhen Wang, Master, Research associate. He is experienced in microPET imaging and animal experiments.

Xinyu Wang

Xinyu Wang, PhD, Associate professor. He is experienced in data analysis and animal experiments.

Junjie Yan

Junjie Yan, PhD, Associate professor. He is experienced in organic synthesis.

Yuping Xu

Yuping Xu, PhD, Professor. He is experienced in designing tracers for tumor diagnosis.

Min Yang

Min Yang, PhD, Professor, Vice president of Jiangsu Institute of Nuclear Medicine. She is experienced in developing molecular imaging agents.