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

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

{"title":"Preliminary evaluation of a novel PSMA-targeting radiopharmaceutical [68Ga]Ga/[177Lu]Lu–NYM032 for theranostic use in prostate cancer","authors":"Haitian Fu, Huihui He, Yanjuan Wang, Wenjin Li, Yihui Luo, Liping Chen, Yuanyuan Mi, Chengwen Sun, Yong Mao, Chunjing Yu","doi":"10.1007/s00259-024-07046-5","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3>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.<h3 data-test=\"abstract-sub-heading\">Methods</h3>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.<h3 data-test=\"abstract-sub-heading\">Results</h3>[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 (SUVmax) 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).<h3 data-test=\"abstract-sub-heading\">Conclusion</h3>[68Ga]Ga/[177Lu]Lu-NYM032 has considerable potential as a novel and powerful theranostic radiopharmaceutical for PCa.<h3 data-test=\"abstract-sub-heading\">Trial registration</h3>The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT06389695) on 29 Apr, 2024.","PeriodicalId":11909,"journal":{"name":"European Journal of Nuclear Medicine and Molecular Imaging","volume":"160 1","pages":""},"PeriodicalIF":8.6000,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Nuclear Medicine and Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00259-024-07046-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

求助全文

约1分钟内获得全文去求助

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.