新型psma靶向放射药物[68Ga]Ga/[177Lu] Lu-NYM032在前列腺癌治疗中的初步评价

IF 8.6 1区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2025-01-02 DOI:10.1007/s00259-024-07046-5

Haitian Fu, Huihui He, Yanjuan Wang, Wenjin Li, Yihui Luo, Liping Chen, Yuanyuan Mi, Chengwen Sun, Yong Mao, Chunjing Yu

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引用次数: 0

摘要

目的研制一种靶向前列腺特异性膜抗原（PSMA）的新型放射药物[68Ga]Ga/[177Lu] Lu-NYM032，并初步评价其在前列腺癌（PCa）治疗中的诊断和治疗潜力。方法首先对PET示踪剂[68Ga] Ga-NYM032在psma阳性异种移植模型（LNCaP模型）中的诊断效果进行评估，然后使用[68Ga] Ga-PSMA617 a比较物对10例PCa患者进行评估。最后，在LNCaP模型中评估[177Lu] Lu-NYM032的治疗潜力。结果[68Ga]Ga/[177Lu] Lu-NYM032耐受性良好，临床前和临床研究均未发现不良事件。[68Ga] Ga-NYM032在LNCaP肿瘤中表现出PSMA特异性和高放射性摄取。[68Ga] Ga-NYM032摄取量（SUVmax）与[68Ga] Ga-PSMA617摄取量在相同的原位病变、相同的p.i.时间点无差异（中位数9.40 vs. 6.85, P = 0.123, n = 8）。与[68Ga] Ga-PSMA617摄取相比，[68Ga] Ga-NYM032在骨转移中的摄取明显更高（中位数5.10 vs. 3.88, P < 0.001, n = 48），在淋巴结转移中的摄取更高（中位数7.81 vs. 5.46, n = 2）。[177Lu] Lu-NYM032在LNCaP模型病变中聚集度高，滞留时间长。[177Lu] Lu-NYM032在LNCaP模型中能抑制肿瘤进展，其治疗效果随着放射剂量的增加而增强（18.5 ~ 74 MBq/小鼠）。高剂量组（74 MBq/只）21 d肿瘤体积明显小于空白对照组（107.14±13.68 mm3 vs. 1351.86±249.98 mm3, P < 0.001, n = 7）。结论[68Ga]Ga/[177Lu]Lu-NYM032作为一种新型有效的前列腺癌治疗放射性药物具有很大的潜力。试验注册本研究的临床评价已于2024年4月29日在Clinicaltrial.gov （NCT06389695）注册。

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Preliminary evaluation of a novel PSMA-targeting radiopharmaceutical [68Ga]Ga/[177Lu]Lu–NYM032 for theranostic use in prostate cancer

Purpose

A novel theranostic radiopharmaceutical targeting prostate-specific membrane antigen (PSMA), [⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu–NYM032, was developed and its diagnostic and therapeutic potential in the treatment of prostate cancer (PCa) was preliminarily evaluated.

Methods

The diagnostic efficacy of the PET tracer [⁶⁸Ga]Ga–NYM032 was first evaluated in PSMA-positive xenograft-bearing models (LNCaP models), followed by evaluation in 10 PCa patients using [⁶⁸Ga]Ga–PSMA617 a comparator. Finally, the therapeutic potential of [¹⁷⁷Lu]Lu–NYM032 was evaluated in LNCaP models.

Results

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu–NYM032 was well-tolerated, and no adverse events were observed in the preclinical and clinical studies. [⁶⁸Ga]Ga–NYM032 demonstrated PSMA specificity and high radioactive uptake in LNCaP tumors. [⁶⁸Ga]Ga–NYM032 uptake (SUV_max) did not differ from [⁶⁸Ga]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 [⁶⁸Ga]Ga–PSMA617 uptake, [⁶⁸Ga]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). [¹⁷⁷Lu]Lu–NYM032 showed high aggregation in the lesions of LNCaP models and long retention times. [¹⁷⁷Lu]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 mm³ vs. 1351.86 ± 249.98 mm³, P < 0.001, n = 7).

Conclusion

[⁶⁸Ga]Ga/[¹⁷⁷Lu]Lu-NYM032 has considerable potential as a novel and powerful theranostic radiopharmaceutical for PCa.

Trial registration

The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT06389695) on 29 Apr, 2024.

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来源期刊

European Journal of Nuclear Medicine and Molecular Imaging 医学-核医学

CiteScore

15.60

自引率

9.90%

发文量

392

审稿时长

3 months

期刊介绍： The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.