Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R–targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with ⁶⁸Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and ⁶⁸Ga-RM2 (⁶⁸Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm³), ⁶⁸Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and ⁶⁸Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered ⁶⁸Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of ⁶⁸Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for ⁶⁸Ga-RM2. Median ⁶⁸Ga-RM2 SUV_max was significantly higher than median ⁶⁸Ga-PSMA-617 SUV_max in the ISUP-2 subgroup (P = 0.01). Conclusion: ⁶⁸Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and ⁶⁸Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.

考虑到局限性前列腺癌的广泛治疗选择（例如主动监测、放射束治疗、局部治疗和根治性前列腺切除术），准确评估原发性前列腺癌病变的侵袭性和定位对于治疗决策至关重要。国家综合癌症网络指南认可前列腺特异性膜抗原 (PSMA) PET/CT 用于高风险原发性前列腺癌的初始分期。胃泌素释放肽受体（GRP-R）是一种在低风险前列腺癌细胞中过度表达的神经肽受体。我们的目标是在初始分期时对 PSMA 和 GRP-R 靶向成像进行首次（据我们所知）前瞻性头对头比较，以了解如何在临床实践中使用或组合 PSMA PET 和 GRP-R PET。方法：这是一项前瞻性、单中心、诊断性横断面成像研究，对 22 名接受 68 Ga-PSMA-617（一种放射性标记的 PSMA 抑制剂）和 68 Ga 的患者进行配对 PET/CT 研究的匿名、隐蔽^和独立^解释。 -RM2（⁶⁸ Ga-DOTA-4-氨基-1-羧甲基哌啶-d -Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2，放射性标记的 GRP-R 拮抗剂）。我们招募了新诊断且经活检证实的前列腺癌患者。没有人接受新辅助激素治疗或化疗，并且所有人都接受了扩大盆腔淋巴结清扫术。组织学结果作为参考。结果：基于病灶的分析（包括病灶 < 0.1 cm ³），⁶⁸ Ga-PSMA-617 PET/CT 检测到所有肿瘤病灶的 74.3% (26/35)，⁶⁸ Ga-RM2 PET/CT 检测到 78.1%（ 25/32；1 名患者无法接受⁶⁸ Ga-RM2 PET/CT）。配对检查显示，32 个病灶中有 21 个（65.6%）2 种示踪剂呈阳性摄取，32 个病灶中有 5 个（15.6%）呈阴性摄取，32 个病灶中有 6 个（18.8%）摄取不一致。当国际泌尿病理学会 (ISUP) 评分至少为 4 与至少 1 ( P < 0.0001) 或 2 ( P  = 0.0002)时， ⁶⁸ Ga-PSMA-617的摄取较高。⁶⁸ Ga-RM2的 ISUP 分数之间的摄取没有显着差异。ISUP-2 亚组中⁶⁸ Ga-RM2 SUV _max中位数显着高于⁶⁸ Ga-PSMA-617 SUV _{max 中位数（} P  = 0.01）。结论：^{第 68 章}Ga-PSMA-617 PET/CT 可用于描绘更高、更具临床意义的 ISUP 评分病变，第^{68 章} Ga-RM2 PET/CT 对低 ISUP 肿瘤的检出率较高。结合 PSMA PET 和 GRP-R PET 可以更好地对前列腺内病变进行分类。