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

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

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

Eur J Nucl Med Mol Imaging. 2025 Jan 2. doi: 10.1007/s00259-024-07046-5. Online ahead of print.

Authors

Haitian Fu^#¹, Huihui He^#¹, Yanjuan Wang¹, Wenjin Li², Yihui Luo², Liping Chen¹, Yuanyuan Mi³, Chengwen Sun³, Yong Mao^{4

5}, Chunjing Yu^{6

7}

Affiliations

¹ Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China.
² Wuxi School of Medicine, Jiangnan University, Wuxi, China.
³ Department of Urological Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China.
⁴ Wuxi School of Medicine, Jiangnan University, Wuxi, China. mydoctorwx@aliyun.com.
⁵ Department of Oncology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China. mydoctorwx@aliyun.com.
⁶ Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China. ycjwxd1978@jiangnan.edu.cn.
⁷ Wuxi School of Medicine, Jiangnan University, Wuxi, China. ycjwxd1978@jiangnan.edu.cn.

^# Contributed equally.

PMID: 39745526
DOI: 10.1007/s00259-024-07046-5

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.

Keywords: NYM032; PSMA; Prostate cancer; Radiopharmaceuticals; Theranostics.

Associated data

ClinicalTrials.gov/NCT06389695