Theranostic methods are changing the standard of care in men with prostate cancer. By enabling targeted imaging and therapy, agents targeting prostate-specific membrane antigen (PSMA) enable both detection and subsequent treatment of recurrent or metastatic prostate cancer. However, a significant fraction of prostate tumors demonstrates heterogeneous, low, or absent expression of PSMA. CD46 is a cell surface antigen that is highly expressed on the surface of prostate cancer cells including those that are PSMA negative.
In a recent publication in Clinical Cancer Research, Wang et al. describe the development of a novel molecular imaging agent targeting CD46, and its application in a variety of preclinical prostate cancer models. The agent, [89Zr]DFO-YS5, acts by targeting a cancer-specific epitope on CD46 and enables imaging in a variety of cell line and patient-derived xenograft models. When used in PET imaging in these models, the researchers found high tumor to background ratios, enabling the detection of prostate cancer with excellent image contrast. An important finding was that [89Zr]DFO-YS5 was able to detect all prostate cancer models tested, including those that are PSMA negative. Moreover, high uptake was seen across all tumor types, including in neuroendocrine prostate cancer patient-derived xenografts. Therefore, [89Zr]DFO-YS5 PET imaging is a highly promising method for the detection of prostate cancer. With an antibody-drug conjugate targeting CD46 now in clinical trials, [89Zr]DFO-YS5 demonstrates great potential for clinical translation as a theranostic agent for the detection of CD46 positive prostate cancer.
Written by: Robert R. Flavell, MD, PhD, Assistant Professor in Residence, Department of Radiology, Section of Nuclear Medicine, University of California San Francisco, San Francisco, California
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Clinical Trial Information: NCT03575819