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.
Haitian Fu  #  1 ,  Huihui He  #  1 ,  Yanjuan Wang  1 ,  Wenjin Li  2 ,  Yihui Luo  2 ,  Liping Chen  1 ,  Yuanyuan Mi  3 ,  Chengwen Sun  3 ,  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. [email protected].
  • 5. Department of Oncology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China. [email protected].
  • 6. Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, Jiangsu Province, 214000, China. [email protected].
  • 7. Wuxi School of Medicine, Jiangnan University, Wuxi, China. [email protected].
  • # 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 (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).

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.
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