Real time transferrin-based PET detects MYC-positive prostate cancer

摘要

Non-invasive biomarkers that detect the activity of important oncogenic drivers could significantly improve cancer diagnosis and management of treatment. The goal of this study was to determine if ⁶⁸Ga-citrate (which avidly binds to circulating transferrin) labeled transferrin (Tf) can detect MYC-positive prostate cancer tumors, since the transferrin receptor is a direct MYC target gene. Positron emission tomography (PET) imaging paired with ⁶⁸Ga-citrate and molecular analysis of preclinical models, human cell-free DNA (cfDNA) and clinical biopsies were conducted to determine whether ⁶⁸Ga-citrate can detect MYC-positive prostate cancer. Importantly, ⁶⁸Ga-citrate detected human prostate cancer models in a MYC-dependent fashion. In patients with castration resistant prostate cancer (CRPC), analysis of cfDNA revealed that all patients with ⁶⁸Ga-citrate avid tumors had a gain of at least one MYC copy number. Moreover, biopsy of two PET avid metastases showed molecular or histological features characteristic of MYC hyperactivity. These data demonstrate that ⁶⁸Ga-citrate targets prostate cancer tumors with MYC hyperactivity. A larger prospective study is ongoing to demonstrate the specificity of ⁶⁸Ga-citrate for tumors with hyperactive MYC.