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.
Disclosure statement
The authors declare that they have no conflict of interest.
Additional information
Funding
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.