简介：α-5 β-3 (αVβ3) 整合素的表达在各种正在进行血管生成的恶性肿瘤中上调。整合素拮抗剂作为诊断探针的发展使得αVβ3整合素成为靶向肿瘤血管生成的合适候选者。本研究的目的是优化放射性标记并评估缀合整联蛋白拮抗剂氨基甲酸酯（IAC）（一种肽模拟物）作为靶向肿瘤血管生成的治疗诊断放射性药物的潜力。方法：DOTAGA [2,2',2" -{10-(2,6-二氧四氢-2H-吡喃-3-基)-1,4,7,10-四氮杂环十二烷-1,4,7-三基的放射性标记} 三乙酸]-IAC 与 [68Ga]Ga、[177Lu]Lu 和 [225Ac]Ac 进行了优化 DOTAGA-IAC 对 αVβ3 受体和癌细胞系的结合亲和力 (Kd) 进行了生物分布研究。对健康 Wistar 大鼠进行了 [177Lu]Lu-DOTAGA-IAC 分布数据的剂量测定分析 [68Ga]Ga-DOTAGA-IAC 和 [18F]FDG 正电子发射断层扫描 (PET/CT) 成像的初步研究。对 5 名经组织病理学证实的乳腺癌患者进行了 PET/CT 结果比较，这些患者的 [68Ga]Ga-DOTAGA-IAC 和 [18F]FDG 结果：制备的放射性药物具有高放射化学纯度 (>99.9%)。 αVβ3 受体蛋白的 Bmax 测量值为 15.02 nM 和 417 fmol：C6 神经胶质瘤细胞的 Bmax 测量值为 115.7 nM 和 295.3 fmol。大鼠生物分布研究表明通过肾脏排泄，部分通过肝胆途径排泄。发现[177Lu]Lu-DOTAGA-IAC的有效剂量为0.17mSv/MBq。对患者的动态研究表明，最佳成像时间为给药后 30-35 分钟。在队列中，[68Ga]Ga-DOTAGA-IAC 检测到所有 5 名患者的主要病变，平均标准摄取值 (SUVmax) 为 3.94 ± 0.58，与 [18F]FDG (SUVmax 13.8 ± 6.53) 相比。结论：该研究表明，DOTAGA-IAC 与 αVβ3 整合素具有很强的结合力，使其成为评估原发性和转移性癌症的有前景的 PET 试剂。试点研究的结果表明 [68Ga]Ga-DOTAGA-IAC PET/CT 在乳腺癌诊断中的潜力。在认识到 DOTAGA-IAC 对于表达 αVβ3 整合素的肿瘤的治疗诊断潜力的同时，需要进一步的临床研究以全面评估治疗效果。

Introduction: The expression of alpha-five beta-three (αVβ3) integrins is upregulated in various malignancies undergoing angiogenesis. The development of integrin antagonists as diagnostic probes makes the αVβ3 integrin a suitable candidate for targeting tumor angiogenesis. The goal of this study was to optimize the radiolabeling and evaluate the potential of conjugated integrin antagonist carbamate (IAC), a peptidomimetic, as a theranostic radiopharmaceutical for targeting tumor angiogenesis. Methodology: Radiolabeling of DOTAGA [2,2',2" -{10-(2,6-dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl} triacetic-acid]-IAC with [68Ga]Ga, [177Lu]Lu, and [225Ac]Ac was optimized. The binding affinity (Kd) of DOTAGA-IAC for the αVβ3 receptor and cancer cell lines was quantified. The biodistribution studies were conducted in healthy Wistar rats. Dosimetry analysis was performed on [177Lu]Lu-DOTAGA-IAC distribution data. A pilot study of [68Ga]Ga-DOTAGA-IAC and [18F]FDG Positron Emission Tomography (PET/CT) imaging was performed in five patients with histopathologically confirmed breast cancer. PET/CT findings were compared between [68Ga]Ga-DOTAGA-IAC and [18F]FDG in these patients. Results: Radiopharmaceuticals were prepared with high radiochemical purity (>99.9%). Kd and Bmax measurements were 15.02 nM and 417 fmol for αVβ3 receptor protein: 115.7 nM and 295.3 fmol for C6 glioma cells. Biodistribution studies in rats suggested the excretion via kidneys and partially through the hepatobiliary route. The effective dose of [177Lu]Lu-DOTAGA-IAC was found to be 0.17 mSv/MBq. The dynamic study in patients revealed the optimal imaging time to be 30-35 mins postadministration. Out of the cohort, [68Ga]Ga-DOTAGA-IAC detected the primary lesions in all five patients with a mean standard uptake value (SUVmax) of 3.94 ± 0.58 compared with [18F]FDG (SUVmax 13.8 ± 6.53). Conclusion: The study demonstrates that DOTAGA-IAC exhibits strong binding to αVβ3 integrin, positioning it as a promising PET agent for assessing primary and metastatic cancers. The outcomes from the pilot study suggest the potential of [68Ga]Ga-DOTAGA-IAC PET/CT in breast carcinoma diagnosis. While recognizing the theranostic potential of DOTAGA-IAC for αVβ3 integrin-expressing tumors, further clinical investigations are warranted to comprehensively assess therapeutic efficacy.