CD46, a protein overexpressed in prostate cancer but scarce in most healthy tissues, has emerged as a promising alternative target, especially for both adenocarcinoma and neuroendocrine subtypes of the diseaseಸ
In preclinical tests, researchers used two agents: 89Zr-DFO-YS5 to spot CD46-rich tumors via PET imaging and 225Ac-Macropa-PEG4-YS5 to treat them. The imaging agent successfully identified tumors, paving the way for targeted therapy. The treatment agent delivered radiation that eradicated small tumors—less than 1 millimeter—uniformly, shrinking them and boosting survival in animal models. Larger tumors over 1 millimeter, however, showed uneven radiation, suggesting early treatment is critical for the best results. This could be vital for patients with tiny, spreading tumors or those at high risk of progression, particularly those with PSMA-negative tumors or liver metastases.
The study emphasized early intervention, showing that treating tumors before they grow too large could significantly improve outcomes. Visual evidence from the experiments, including bioluminescence, PET/CT scans, radiation dose maps, and DNA damage markers in liver tumors, underscored the therapy’s potential. For patients who don’t respond to PSMA-based treatments, this could open new doors.
Clinical trials are already underway, including a phase I trial testing the imaging agent in men with prostate cancer and others exploring related CD46-targeted therapies.

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