CHANGSHA — Researchers at Xiangya Hospital in Changsha presented a novel theranostic approach targeting RET, a newly identified biomarker for neuroendocrine prostate cancer, at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting. The approach enables high-contrast PET imaging and effective, safe treatment for this aggressive malignancy.
Neuroendocrine prostate cancer is an aggressive, treatment-resistant subtype that frequently develops as an evolution of castration-resistant prostate cancer. It often expresses low levels of PSMA or is PSMA negative, making it difficult to detect with current PSMA-based imaging and leading to less effective treatment outcomes.
The research team identified RET as a candidate surface marker for neuroendocrine prostate cancer based on previous studies. RET expression was validated by immunohistochemistry in 134 human prostate specimens. Researchers then selected RET-L7 as a binding peptide for theranostic development.
In preclinical evaluations, 68Ga-DOTA-RET-L7 PET/CT and 177Lu-DOTA-RET-L7 therapy were tested in both RET-positive and RET-negative xenografts. The team conducted blocking, biodistribution, survival, and toxicity studies as part of their assessment. 68Ga-DOTA-RET-L7 demonstrated high, specific uptake in RET-positive tumors compared to RET-negative tumors, along with strong self-blockade and rapid blood clearance.
A single dose of 177Lu-DOTA-RET-L7 produced a dose-dependent survival benefit without hematologic or organ toxicity. "RET is a clinically relevant neuroendocrine prostate cancer-selective surface target," said Yongxiang Tang, associate professor and deputy director, Department of Nuclear Medicine, Xiangya Hospital, Central South University. "This preclinical work supports translation of the RET-targeted theranostic approach for PSMA-negative prostate cancer." Tang said.
First-in-human imaging is currently being conducted as part of an investigator-initiated clinical study. Broader patient access to the RET-targeted theranostic approach will require additional safety and dosimetry evaluation, larger clinical validation, and regulatory approvals.