A newly identified biomarker called RET is showing promise as both an imaging target and a treatment pathway for one of the most aggressive and hard-to-detect forms of prostate cancer. Researchers say the approach could help patients who don’t respond to conventional molecular imaging.
A research team from Xiangya Hospital, Central South University in Changsha, China, has developed a dual-purpose strategy — capable of both detecting and treating neuroendocrine prostate cancer — by zeroing in on a protein called RET that standard imaging tools often miss entirely. The findings were presented at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting, drawing significant attention for their potential to change how physicians manage one of prostate cancer’s most stubborn subtypes.
Why Standard Imaging Falls Short
Neuroendocrine prostate cancer is a particularly aggressive form of the disease that frequently emerges as castration-resistant prostate cancer progresses over time. Unlike the more common prostate cancer subtypes, it tends to produce very low levels of prostate-specific membrane antigen — or PSMA — or none at all. That’s a problem because the most widely used modern imaging techniques and targeted therapies are built around PSMA as a marker. When PSMA is absent, the cancer can essentially fly under the radar.
Lead author Yongxiang Tang, an associate professor and deputy director in the Department of Nuclear Medicine at Xiangya Hospital at Central South University, framed the clinical stakes clearly.
“Patients with neuroendocrine prostate cancer face a major challenge because this cancer can hide from PSMA-based scans and therapies,” Tang said in a news release. “In our study, we aimed to identify a neuroendocrine prostate cancer biomarker and develop a theranostic pair for PET imaging and radioligand therapy.”
Identifying RET as a Target
Drawing on earlier research, the team identified RET — a cell-surface receptor protein — as a strong candidate marker for this cancer subtype. To confirm its relevance, researchers validated RET expression using immunohistochemistry across 134 human prostate tissue specimens, establishing that the protein is genuinely present and clinically meaningful in neuroendocrine prostate cancer cases.
From there, the team selected a binding peptide called RET-L7 and built two companion agents around it: one for imaging, known as ⁶⁸Ga-DOTA-RET-L7, and one for therapy, known as ¹⁷⁷Lu-DOTA-RET-L7. These agents are the core of what researchers call a theranostic pair — a matched set of tools that use the same molecular target for both diagnosis and treatment, a concept that has gained momentum in precision oncology over the past decade.
What the Experiments Showed
The imaging agent, ⁶⁸Ga-DOTA-RET-L7, was tested in both RET-positive and RET-negative tumor models using PET/CT scanning. It demonstrated high, specific uptake in RET-positive tumors while showing much weaker signal in RET-negative tumors — an important distinction that confirms the agent is homing in on the right target rather than lighting up indiscriminately. Researchers also observed strong self-blockade effects and rapid clearance from the bloodstream, both of which are desirable properties for a clinical imaging agent because they reduce background noise and limit unnecessary radiation exposure.
On the treatment side, a single dose of ¹⁷⁷Lu-DOTA-RET-L7 produced measurable, dose-dependent improvements in survival in the animal models. Equally important, the therapy did not cause significant damage to blood cells or major organs — a finding that matters enormously when translating a new radioligand therapy to human patients, where toxicity is a primary safety concern.
“RET is a clinically relevant neuroendocrine prostate cancer-selective surface target,” Tang added. “This preclinical work supports translation of the RET-targeted theranostic approach for PSMA-negative prostate cancer.”
Why It Matters for Patients and Researchers
For patients whose cancer has evolved into the neuroendocrine subtype — often after prolonged treatment for earlier-stage prostate cancer — current options are limited. PSMA-based theranostics like lutetium-177 PSMA-617 have transformed care for many patients with castration-resistant prostate cancer, but they offer little benefit when PSMA expression is low or absent. A RET-targeted alternative could fill that gap, giving clinicians a viable molecular imaging and treatment option for a group that currently has very few.
The research also fits into a broader trend in nuclear medicine toward personalized, target-driven therapy. Rather than using chemotherapy or radiation that affects the entire body, radioligand therapies deliver a radioactive payload directly to cancer cells expressing a specific surface protein — theoretically increasing effectiveness while reducing collateral damage to healthy tissue.
Next Steps: From Lab to Clinic
The team has already moved beyond preclinical models. First-in-human imaging using the RET-targeted tracer is currently underway as part of an investigator-initiated clinical study — a meaningful step that signals confidence in the approach’s safety profile. However, researchers caution that broader patient access will require additional safety and dosimetry data, larger-scale clinical validation, and regulatory review processes that can take years.
The study, published as an abstract in the Journal of Nuclear Medicine, included researchers from Inselspital at the University of Bern in Switzerland.