Annotating MYC oncogene status with (89)Zr-transferrin imaging

A non-invasive technology that quantitatively measures the activity of oncogenic signaling pathways could broadly impact cancer diagnosis and treatment using targeted therapies. Here we describe the development of (89)Zr-desferrioxamine transferrin ((89)Zr-Tf), a novel positron emission tomography (PET) radiotracer that binds the transferrin receptor 1 (TFRC, CD71) with high avidity. (89)Zr-Tf produces high contrast PET images that quantitatively reflect treatment-induced changes in MYC-regulated TFRC expression in a MYC oncogene-driven prostate cancer xenograft model. Moreover, (89)Zr-Tf imaging can detect the in situ development of prostate cancer in a transgenic MYC prostate cancer model, as well as prostatic intraepithelial neoplasia (PIN) prior to histological or anatomic evidence of invasive cancer. These preclinical data establish (89)Zr-Tf as a sensitive tool for non-invasive measurement of oncogene-driven TFRC expression in prostate, and potentially other cancers, with prospective near-term clinical application.