Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California
Department of Medicine, University of California, San Francisco, San Francisco, California.
J Nucl Med. 2019 Jul;60(7):910-916. doi: 10.2967/jnumed.118.220715. Epub 2018 Nov 21.
Agents targeting prostate-specific membrane antigen (PSMA) comprise a rapidly emerging class of radiopharmaceuticals for diagnostic imaging of prostate cancer. Unlike most other PSMA agents with a urea backbone, CTT1057 is based on a phosphoramidate scaffold that irreversibly binds to PSMA. We conducted a first-in-humans phase I study of CTT1057 in patients with localized and metastatic prostate cancer. Two patient cohorts were recruited. Cohort A patients had biopsy-proven localized prostate cancer preceding radical prostatectomy, and cohort B patients had metastatic castration-resistant prostate cancer. Cohort A patients were imaged at multiple time points after intravenous injection with 362 ± 8 MBq of CTT1057 to evaluate the kinetics of CTT1057 and estimate radiation dose profiles. Mean organ-absorbed doses and effective doses were calculated. CTT1057 uptake in the prostate gland and regional lymph nodes was correlated with pathology, PSMA staining, and the results of conventional imaging. In cohort B, patients were imaged 60-120 min after injection of CTT1057. PET images were assessed for overall image quality, and areas of abnormal uptake were contrasted with conventional imaging. In cohort A ( = 5), the average total effective dose was 0.023 mSv/MBq. The kidneys exhibited the highest absorbed dose, 0.067 mGy/MBq. The absorbed dose of the salivary glands was 0.015 mGy/MBq. For cohort B ( = 15), CTT1057 PET detected 97 metastatic lesions, and 44 of 56 bone metastases detected on CTT1057 PET (78.5%) were also detectable on bone scanning. Eight of 32 lymph nodes positive on CTT1057 PET (25%) were enlarged by size criteria on CT. CTT1057 is a promising novel phosphoramidate PSMA-targeting F-labeled PET radiopharmaceutical that demonstrates similar biodistribution to urea-based PSMA-targeted agents, with lower exposure to the kidneys and salivary glands. Metastatic lesions are detected with higher sensitivity on CTT1057 imaging than on conventional imaging. Further prospective studies with CTT1057 are warranted to elucidate its role in cancer imaging.
靶向前列腺特异性膜抗原（PSMA）的药物包括一类快速发展的放射性药物，用于前列腺癌的诊断成像。与大多数具有尿素骨架的其他 PSMA 药物不同，CTT1057 基于膦酰胺骨架，可与 PSMA 不可逆结合。我们在局部和转移性前列腺癌患者中进行了 CTT1057 的首次人体 I 期研究。招募了两批患者。队列 A 的患者在根治性前列腺切除术前通过活检证实患有局限性前列腺癌，而队列 B 的患者患有转移性去势抵抗性前列腺癌。队列 A 的患者在静脉注射 362 ± 8 MBq 的 CTT1057 后多个时间点进行成像，以评估 CTT1057 的动力学并估计辐射剂量分布。计算平均器官吸收剂量和有效剂量。前列腺和局部淋巴结的 CTT1057 摄取与病理、PSMA 染色和常规成像结果相关。在队列 B 中，患者在注射 CTT1057 后 60-120 分钟进行成像。评估 PET 图像的整体图像质量，并将异常摄取区域与常规成像进行对比。在队列 A（n = 5）中，平均总有效剂量为 0.023 mSv/MBq。肾脏的吸收剂量最高，为 0.067 mGy/MBq。唾液腺的吸收剂量为 0.015 mGy/MBq。对于队列 B（n = 15），CTT1057 PET 检测到 97 个转移性病变，其中 44 个 CTT1057 PET 检测到的骨转移（78.5%）也可在骨扫描中检测到。CTT1057 PET 阳性的 32 个淋巴结中有 8 个（25%）的淋巴结大小符合标准。CTT1057 是一种有前途的新型膦酰胺 PSMA 靶向 F 标记 PET 放射性药物，其生物分布与基于尿素的 PSMA 靶向药物相似，肾脏和唾液腺的暴露量较低。与常规成像相比，CTT1057 成像可检测到更高灵敏度的转移性病变。需要进一步进行 CTT1057 的前瞻性研究，以阐明其在癌症成像中的作用。
