Real-time diagnosis of sampled lesions in targeted biopsy of prostate Cancer using a novel tracer [64Cu] Cu-DOTA-PSMA-3Q: a pilot preclinical study,European Journal of Nuclear Medicine and Molecular Imaging

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Real-time diagnosis of sampled lesions in targeted biopsy of prostate Cancer using a novel tracer [64Cu] Cu-DOTA-PSMA-3Q: a pilot preclinical study
European Journal of Nuclear Medicine and Molecular Imaging ( IF 8.6 ) Pub Date : 2024-11-30 , DOI: 10.1007/s00259-024-07000-5
Jingfeng Zhang, Shaoxi Niu, Yachao Liu, Xiaojun Zhang, Xiaohui Luan, Huanhuan Liu, Yue Pan, Xiaodan Xu, Shina Wu, Yuan Wang, Zhiqiang Chen, Baojun Wang, Xu Zhang, Ruimin Wang, Jinming Zhang, Baixuan Xu

Purpose

Prostate-specific membrane antigen positron emission tomography (PSMA-PET) guided targeted biopsy has shown potential for detecting more prostate cancer (PCa) cases. However, relying exclusively on imaging may risk missing lesions, an issue that could be addressed by incorporating radiation-guided technology. Accordingly, we aimed to develop a novel PSMA radiotracer with a long half-life, [⁶⁴Cu]Cu-DOTA-PSMA-3Q, and evaluate its targeting accuracy. Additionally, this research explored the practicability of real-time lesion verification during surgical interventions.

Methods

In this study, we synthesized the radiotracer [⁶⁴Cu]Cu-DOTA-PSMA-3Q and verified its PSMA specificity and safety. We prospectively enrolled 18 patients with suspected PCa for PET/CT imaging to assess the efficacy of PCa detection; 10 patients underwent targeted biopsy combined with standard template biopsy at an interval of 24 h after injection. The radioactivity of the biopsy tissue was quantified in counts per minute (CPM) using a gamma spectrometer intraoperatively.

Results

The efficacy and specificity of [⁶⁴Cu]Cu-DOTA-PSMA-3Q were confirmed through preclinical cell and animal studies. In clinical settings, PET/CT imaging performed 2 h after injection visualized all of the PSMA-positive lesions both within and outside the prostate. The assessment of human organ radiation exposure indicated that the kidneys received the highest absorbed dose, followed by the bladder wall, salivary glands, and liver. In 10 patients, a total of 132 biopsy cores were extracted, with 53 cores histologically confirmed as PCa. The median CPM for PCa tissues was significantly greater at 134,148 CPM compared to 18,39 CPM for normal prostate tissues (P < 0.001). Receiver operating characteristic (ROC) curve analysis yielded an AUC of 0.8837, suggesting high diagnostic accuracy. The optimal diagnostic cut-off was established at 66 CPM, achieving a sensitivity of 77.36%.

Conclusions

Radiation-guided technology using [⁶⁴Cu]Cu-DOTA-PSMA-3Q improves the reliability of PSMA-PET image-guided biopsy, enables instant confirmation of sample lesions during surgical procedures, and holds potential for achieving optimized puncture outcomes.