Fu Haitian, He Huihui, Wang Yanjuan, Li Wenjin, Luo Yihui, Chen Liping, Mi Yuanyuan, Sun Chengwen, Mao Yong, Yu Chunjing
Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China.
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Eur J Nucl Med Mol Imaging. 2025 Apr;52(5):1671-1684. doi: 10.1007/s00259-024-07046-5. Epub 2025 Jan 2.
A novel theranostic radiopharmaceutical targeting prostate-specific membrane antigen (PSMA), [Ga]Ga/[Lu]Lu-NYM032, was developed and its diagnostic and therapeutic potential in the treatment of prostate cancer (PCa) was preliminarily evaluated.
The diagnostic efficacy of the PET tracer [Ga]Ga-NYM032 was first evaluated in PSMA-positive xenograft-bearing models (LNCaP models), followed by evaluation in 10 PCa patients using [Ga]Ga-PSMA617 a comparator. Finally, the therapeutic potential of [Lu]Lu-NYM032 was evaluated in LNCaP models.
[Ga]Ga/[Lu]Lu-NYM032 was well-tolerated, and no adverse events were observed in the preclinical and clinical studies. [Ga]Ga-NYM032 demonstrated PSMA specificity and high radioactive uptake in LNCaP tumors. [Ga]Ga-NYM032 uptake (SUV) did not differ from [Ga]Ga-PSMA617 uptake in the same in situ lesions at the same p.i. time point (median 9.40 vs. 6.85, P = 0.123, n = 8). Compared with [Ga]Ga-PSMA617 uptake, [Ga]Ga-NYM032 uptake was significantly higher in osseous metastases (median 5.10 vs. 3.88, P < 0.001, n = 48), and higher in lymph node metastases (median 7.81 vs. 5.46, n = 2). [Lu]Lu-NYM032 showed high aggregation in the lesions of LNCaP models and long retention times. [Lu]Lu-NYM032 could inhibit tumor progression in LNCaP models, and its therapeutic efficiency strengthened with increasing radio-dosage (18.5-74 MBq/mouse). The tumor volume in the high radio-dosage treatment group (74 MBq/mouse) was significantly smaller than that in the blank control group at 21 days p.i. (107.14 ± 13.68 mm vs. 1351.86 ± 249.98 mm, P < 0.001, n = 7).
[Ga]Ga/[Lu]Lu-NYM032 has considerable potential as a novel and powerful theranostic radiopharmaceutical for PCa.
The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT06389695) on 29 Apr, 2024.
研发一种新型的靶向前列腺特异性膜抗原（PSMA）的诊疗放射性药物[Ga]Ga/[Lu]Lu-NYM032，并初步评估其在前列腺癌（PCa）治疗中的诊断和治疗潜力。
首先在PSMA阳性异种移植模型（LNCaP模型）中评估PET示踪剂[Ga]Ga-NYM032的诊断效果，随后使用[Ga]Ga-PSMA617作为对照在10例PCa患者中进行评估。最后，在LNCaP模型中评估[Lu]Lu-NYM032的治疗潜力。
[Ga]Ga/[Lu]Lu-NYM032耐受性良好，在临床前和临床研究中均未观察到不良事件。[Ga]Ga-NYM032在LNCaP肿瘤中表现出PSMA特异性和高放射性摄取。在相同的注射后时间点，相同原位病变中[Ga]Ga-NYM032的摄取（SUV）与[Ga]Ga-PSMA617的摄取无差异（中位数9.40对6.85，P = 0.123，n = 8）。与[Ga]Ga-PSMA617摄取相比，[Ga]Ga-NYM032在骨转移中的摄取显著更高（中位数5.10对3.88，P < 0.001，n = 48），在淋巴结转移中也更高（中位数7.81对5.46，n = 2）。[Lu]Lu-NYM032在LNCaP模型的病变中显示出高聚集性和长滞留时间。[Lu]Lu-NYM032可抑制LNCaP模型中的肿瘤进展，其治疗效果随放射剂量增加（18.5 - 74 MBq/小鼠）而增强。在注射后21天，高放射剂量治疗组（74 MBq/小鼠）的肿瘤体积显著小于空白对照组（107.14 ± 13.68 mm对1351.86 ± 249.98 mm，P < 0.001，n = 7）。
[Ga]Ga/[Lu]Lu-NYM032作为一种新型且强大的PCa诊疗放射性药物具有相当大的潜力。
本研究的临床评估于2024年4月29日在Clinicaltrial.gov（NCT06389695）注册。
