SNMMI: Theranostic approach may treat PSMA-negative prostate cancer

A novel theranostic approach presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2026 annual meeting could help with prostate cancer treatment. 

In his June 2 presentation, Yongxiang Tang, PhD, from Xiangya Hospital at Central South University in Changsha, Hunan, China, shared results indicating how the approach targets the rearranged during transfection (RET) biomarker in neuroendocrine prostate cancer. This makes way for high-contrast PET imaging and effective, safe treatment, he added. 

“This preclinical work supports translation of the RET-targeted theranostic approach for [prostate-specific membrane antigen]-negative prostate cancer,” Tang said. 

Neuroendocrine prostate cancer is challenging to detect and treat since this form of cancer often expresses low levels of PSMA or is PSMA-negative. It is an aggressive, treatment-resistant subtype that usually appears as an evolution of castration-resistant prostate cancer.  

Tang and fellow researchers sought to find a neuroendocrine prostate cancer biomarker and develop a theranostic pair for PET imaging and radioligand therapy.

The researchers used previous patient-derived studies and named receptor tyrosine kinase RET as a candidate surface marker. They validated RET expression via immunohistochemistry in 134 human prostate specimens, focusing on the RET-L7 peptide. From there, the researchers evaluated 68Ga-DOTA-RET-L7 PET/CT and 177Lu-DOTA-RET-L7 therapy in RET-positive and RET-negative xenografts from rodent models. 

Tang reported that 68Ga-DOTA-RET-L7 showed high, specific uptake in RET-positive tumors versus RET-negative tumors. This also included strong self-blockade and rapid blood clearance.

Tang also said a single dose of 177Lu-DOTA-RET-L7 produced dose-dependent survival benefits with no significant hematologic or organ toxicity. 

Additionally, RET staining was enriched in most neuroendocrine prostate cancer cases (85.7%, 12/14). However, this was rare in adenocarcinoma (6.4%, 5/78), benign hyperplasia (4.5%, 1/22), and normal prostate (0/20). 

RET-targeted PET tracer highlights neuroendocrine prostate cancer tumors. Representative PET imaging shows strong tumor uptake of the RET-binding peptide tracer [⁶⁸Ga]Ga-DOTA-RET-L7 in a neuroendocrine prostate cancer (NEPC) model, supporting highly specific, high-contrast detection.Yongxiang Tang, PhD, and SNMMI

Tang said the team is working on a first-in-human imaging study, adding that broader patient access will need more safety and dosimetry evaluation, larger clinical validation, and regulatory approvals. 

Still, he said that RET-L7 peptide theranostics allows for high-contrast PET imaging and effective, well-tolerated radioligand therapy. The results support translation for PSMA-negative prostate cancer, Tang added. 

Check out AuntMinnie’s full coverage of SNMMI 2026 on our ShowCast.