Development and clinical evaluation of ⁶⁴Cu-RAX301: A next-generation PSMA PET tracer for enhanced detection of metastatic prostate cancer
Presenter: Guangzhou Han, PhD Session: Molecular Imaging, Radiomics, and Theranostics Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Fei Chen 1 , Min Hong 2 , Xupeng Hu 2 , Yang Cao 2 , Jie Li 1 , Zhao Li 1 , Shuanglong Liu 2 , Guangzhou Han 2 , Suping Li 1 , Gang Chen 2 1 Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, China, 2 RadAlliance Therapeutics Inc., San Diego, CA
Abstract
Prostate-specific membrane antigen (PSMA) PET imaging is widely used for diagnosing and staging prostate cancer, yet the currently approved ⁶⁸Ga- and ¹⁸F-labeled tracers are limited by short half-lives and high urinary excretion, which can obscure small pelvic lesions. To overcome these challenges, ⁶⁴Cu-RAX301 was developed as a high-affinity PSMA PET tracer designed for improved biochemical stability and extended imaging flexibility. The RAX301 precursor and its nat Cu-RAX301 analog were synthesized with high purity, and radiolabeling with ⁶⁴Cu was optimized to achieve high molar activity (≥2000 mCi/μmol) and radiochemical purity (>95%), and remaining stable for over 48 hours post-formulation. Surface plasmon resonance revealed sub-picomolar binding affinity (Kd nat Cu-RAX301, markedly stronger than PSMA-617 (22 pM). Consistent with this, cell-based assays showed two-fold higher affinity, 1.5-fold greater uptake, and four-fold higher internalization compared with ⁶⁴Cu-PSMA-617 (≈80% vs. ≈20%). In LNCaP xenograft mice, ⁶⁴Cu-RAX301 demonstrated intense and persistent tumor uptake, with tumor-to-muscle ratios exceeding one hundred at 4 hours post-injection. PET imaging in Macaca fascicularis revealed primarily renal clearance with minimal uptake in other organs. In a first-in-human study of ten patients with metastatic castration-resistant prostate cancer (mCRPC), sequential PET/CT scans were performed first with ⁶⁸Ga-PSMA-11 (5 mCi; imaging at 1 hour post-injection) and then with ⁶⁴Cu-RAX301 (5 mCi; imaging at 4 and 24 hours post-injection), separated by 1-7 days. ⁶⁴Cu-RAX301 detected all lesions identified by ⁶⁸Ga-PSMA-11 while providing higher lesion uptake and superior tumor-to-background contrast. Notably, ⁶⁴Cu-RAX301 revealed numerous additional small lesions at various sites, including pelvic lymph node metastases that were frequently missed by ⁶⁸Ga-PSMA-11 due to early bladder activity. The tracer exhibited an excellent safety profile with no significant adverse events. Collectively, these preclinical and early clinical findings demonstrate that ⁶⁴Cu-RAX301 possesses ultra-high PSMA affinity, favorable pharmacokinetics, and enhanced lesion visualization compared with ⁶⁸Ga-PSMA-11, supporting its potential as a next-generation PSMA PET imaging agent with improved sensitivity and diagnostic performance in metastatic prostate cancer. Ongoing clinical studies aim to further define its diagnostic impact and broader clinical utility.
Disclosure
F. Chen, None.. M. Hong, None.. X. Hu, None.. Y. Cao, None.. J. Li, None.. Z. Li, None.. S. Liu, None.. G. Han, None.. S. Li, None.. G. Chen, None.
Cited in
Control: 2075 · Presentation Id: 8589 · Meeting 21436