Optimizing the performance of 68Ga labeled FSHR ligand in prostate cancer model by Co-Administration of aprotinin
Optimizing the performance of 68Ga labeled FSHR ligand in prostate cancer model by Co-Administration of aprotinin
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DOI：
10.1080/09553002.2022.2063431
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发表时间：
2022-04-13
影响因子：
2.6
通讯作者：
Yang，Min
中科院分区：
文献类型：
--
作者：
Pan，Donghui;Wang，Lizhen;Yang，Min
目的放射性标记的FSH1多肽是一种潜在的FSHR成像特异性探针。然而，肿瘤的适度摄取和快速洗脱可能会限制其广泛使用。本研究制备了68Ga标记的修饰FSH1类似物，并在有无抑肽酶的前列腺癌模型中测定了其成像特性。结果成功制备了68Ga-NOTA-MAL-FSH4。68Ga-NOTA-MAL-FSH4与FSH1的IC50值为139.4 ± 1.16 NM。使用68Ga标记的示踪剂后，PC-3前列腺癌可见。体外反相高效液相分析表明，血浆、肝脏和肿瘤组织中完整多肽的平均百分含量分别为8.30%、9.57%和7.06%。在抑肽酶存在下，完整多肽的含量分别增加到34.32%、20.63%和15.39%。MicroPET图像显示，联合应用100 μg、200 μg和400 μg酶抑制剂60min后，PC-3肿瘤的摄取分别为2.91 ± 0.21%ID/g、3.89 ± 0.16%ID/g和9.21 ± 0.22%ID/g。结论在丝氨酸蛋白酶抑制剂的辅助下，68Ga标记多肽的性能得到优化，为进一步临床应用奠定了基础。
PurposeRadiolabeled 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.MethodsNOTA-MAL-FSH4 was synthesized and labeled with68Ga. The pharmacokinetic profile of the peptide after co-administration with aprotinin was determined through metabolism analyses and microPET imaging.Results68Ga-NOTA-MAL-FSH4 was successfully prepared. The IC50 value of displacement68Ga-NOTA-MAL-FSH4 with FSH1 was 139.4 ± 1.16 nM. The PC-3 prostate tumor was visible after administration of the68Ga 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.ConclusionWith the aid of a serine protease inhibitor, the performance of the68Ga labeled peptide was optimized, which may benefit further clinical application.