The gastrin-releasing peptide receptor (GRPr) is overexpressed in prostate cancer (PCa) cells, making it an excellent tool for targeted imaging. The ⁶⁸Ga-labeled GRPr antagonist SB3 has shown excellent results in preclinical and clinical studies and was selected for further clinical investigation. The aims of this phase I study were to investigate ⁶⁸Ga-SB3 PET/CT imaging of primary PCa tumors and assess safety. More aims included an investigation of biodistribution and dosimetry and a comparison with pathology and GRPr expression. Methods: Ten therapy-naïve, biopsy-confirmed PCa patients planned for prostatectomy were included. A 3-h extensive PET/CT imaging protocol was performed within 2 wk before prostatectomy. Prostate tissue was evaluated for tumor localization and Gleason score, and in vitro autoradiography was performed to determine GRPr expression. Available MRI scans performed within 3 mo before the study were matched. For dosimetry, residence times were estimated and effective dose to the body as well as absorbed doses to organs were calculated using the IDAC dose model, version 2.1. Results: Administration of ⁶⁸Ga-SB3 (187.4 ± 40.0 MBq, 40 ± 5 μg) was well tolerated; no significant changes in vital signs or laboratory results were observed. ⁶⁸Ga-SB3 PET/CT showed lesions in 8 of 10 patients. Pathologic analysis revealed a total of 16 tumor lesions, of which PET/CT showed 14, resulting in a sensitivity of 88%. ⁶⁸Ga-SB3 PET/CT imaging showed uptake in 2 large prostatic intraepithelial neoplasia foci, considered a precursor to PCa, resulting in an 88% specificity. Autoradiography of tumor lesions revealed heterogeneous GRPr expression and was negative in 4 patients. Both PET/CT-negative patients had a GRPr-negative tumor. In autoradiography-positive tumors, the level of GRPr expression showed a significant correlation to tracer uptake on PET/CT. Dosimetry calculations estimated the effective dose to be 0.0144 mSv/MBq, similar to other ⁶⁸Ga-labeled radiopeptides. The highest absorbed dose was detected in the physiologic GRPr-expressing pancreas (0.198 mGy/MBq), followed by the bladder wall and kidneys. Conclusion: ⁶⁸Ga-SB3 PET/CT is a safe imaging method and a promising tool for early PCa imaging.

胃泌素释放肽受体 (GRPr) 在前列腺癌 (PCa) 细胞中过度表达，使其成为靶向成像的绝佳工具。⁶⁸ Ga标记的GRPr拮抗剂SB3在临床前和临床研究中均显示出优异的效果，并被选中用于进一步的临床研究。这项 I 期研究的目的是调查原发性 PCa 肿瘤的⁶⁸ Ga-SB3 PET/CT 成像并评估安全性。更多目标包括生物分布和剂量学研究以及与病理学和 GRPr 表达的比较。方法：包括 10 名计划进行前列腺切除术的初治、活检证实的 PCa 患者。在前列腺切除术前 2 周内进行了 3 小时的广泛 PET/CT 成像方案。评估前列腺组织的肿瘤定位和 Gleason 评分，并进行体外放射自显影以确定 GRPr 表达。匹配研究前 3 个月内进行的可用 MRI 扫描。对于剂量测定，使用 IDAC 剂量模型 2.1 版估计停留时间并计算对身体的有效剂量以及对器官的吸收剂量。结果：⁶⁸ Ga-SB3 (187.4 ± 40.0 MBq, 40 ± 5 μg) 的给药耐受性良好；没有观察到生命体征或实验室结果的显着变化。⁶⁸Ga-SB3 PET/CT 显示 10 名患者中有 8 名出现病变。病理分析共发现16个肿瘤病灶，其中PET/CT显示14个，敏感性为88%。⁶⁸ Ga-SB3 PET/CT 成像显示在 2 个大的前列腺上皮内瘤变病灶中摄取，被认为是 PCa 的前体，导致 88% 的特异性。肿瘤病变的放射自显影显示 GRPr 表达异质，4 例患者为阴性。两名 PET/CT 阴性患者均患有 GRPr 阴性肿瘤。在放射自显影阳性肿瘤中，GRPr 表达水平与 PET/CT 上的示踪剂摄取显着相关。剂量学计算估计有效剂量为 0.0144 mSv/MBq，与其他⁶⁸Ga 标记的放射性肽。在表达 GRPr 的生理胰腺中检测到最高吸收剂量 (0.198 mGy/MBq)，其次是膀胱壁和肾脏。结论： ⁶⁸ Ga-SB3 PET/CT是一种安全的成像方法，是早期PCa成像的一种很有前景的工具。