医学
前列腺癌
体内分布
核医学
谷氨酸羧肽酶Ⅱ
前列腺
免疫组织化学
不利影响
Pet成像
正电子发射断层摄影术
癌症
放射科
标准摄取值
临床试验
内科学
肿瘤科
前瞻性队列研究
衍生工具(金融)
病理
泌尿科
前列腺特异性抗原
功能成像
体内
成像技术
显像剂
染色
作者
Guochang Wang,Yuxin Lai,Dongning Chen,Wenbin Jin,Yang Luo,Yumeng Peng,Hank F. Kung,Lin Zhu,Jie Zang,Ning Xu,Weibing Miao,Guochang Wang,Yuxin Lai,Dongning Chen,Wenbin Jin,Yang Luo,Yumeng Peng,Hank F. Kung,Lin Zhu,Jie Zang
出处
期刊:Journal of nuclear medicine
[Society of Nuclear Medicine and Molecular Imaging]
日期:2025-11-20
卷期号:: jnumed.125.270703-jnumed.125.270703
标识
DOI:10.2967/jnumed.125.270703
摘要
Our team previously reported a preclinical study of 2 novel prostate-specific membrane antigen (PSMA)-targeted compounds that incorporate a hypoxia-sensitive nitroimidazole (NI) moiety-6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid-PSMA-093 (AZ-093) and its hypoxia-responsive derivative 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid-NI-PSMA-093 (AZ-NI-093). This prospective trial aims to evaluate the clinical value of both agents in patients with prostate cancer, specifically exploring the impact of NI on tumor uptake. Methods: Sixty patients were enrolled in this PET/CT imaging study. Thirty patients underwent a head-to-head comparison of [68Ga]Ga-AZ-093 with [68Ga]Ga-PSMA-11 or [68Ga]Ga-PSMA-617, and 30 patients underwent a head-to-head comparison of [68Ga]Ga-AZ-NI-093 with [68Ga]Ga-AZ-093. The number of tumors and SUV for tumors and organs were measured and recorded. SUVmax differences between [68Ga]Ga-AZ-NI-093 and [68Ga]Ga-AZ-093 PET/CT were calculated for further analysis. Immunohistochemical staining for hypoxia-inducible factor 1 was performed on 12 surgical specimens of intraprostatic tumors. Results: All patients tolerated [68Ga]Ga-based PET/CT scans without adverse effects. The initial biodistribution of [68Ga]Ga-AZ-093 and [68Ga]Ga-AZ-NI-093 in humans, as assessed by PET/CT, was comparable to that of other PSMA-targeted radiopharmaceuticals, with respective effective absorbed doses of 0.0128 ± 0.00594 and 0.0160 ± 0.000869 mSv/MBq. [68Ga]Ga-AZ-093 exhibited higher tumor uptake 60 min after injection compared with [68Ga]Ga-PSMA-11 (SUVmax, 22.2 ± 10.8 vs. 20.4 ± 14.8; P = 0.025) and [68Ga]Ga-PSMA-617 (SUVmax, 20.1 ± 12.7 vs. 10.8 ± 8.7; P < 0.001), while maintaining comparable tumor detection rates. [68Ga]Ga-AZ-NI-093 showed further improved tumor uptake relative to [68Ga]Ga-AZ-093 at 60 min (SUVmax, 17.8 ± 14.0 vs. 16.3 ± 11.5; P = 0.009) and 150 min (31.3 ± 18.5 vs. 28.7 ± 17.5; P = 0.003), especially in large-volume, high-grade intraprostatic tumor and metastatic sites. The expression of hypoxia-inducible factor 1 in tumors, as an indicator of hypoxia, demonstrated a significant association with International Society of Urological Pathology grade (r = 0.519; P = 0.038) and difference in SUVmax (r = 0.629; P = 0.023). Conclusion: Both [68Ga]Ga-AZ-093 and [68Ga]Ga-AZ-NI-093 represent promising PSMA-targeted radiopharmaceuticals. [68Ga]Ga-AZ-NI-093 demonstrated potential in targeting hypoxic tumor tissues. Future studies with larger sample sizes are needed to further explore the clinical value of these radiopharmaceuticals.
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