Noninvasive 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 whether 68Ga-citrate (which avidly binds to circulating transferrin) can detect MYC-positive prostate cancer tumors, as the transferrin receptor is a direct MYC target gene. 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, 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 histologic 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. Implications: Noninvasive measurement of MYC activity with quantitative imaging modalities could substantially increase our understanding of the role of MYC signaling in clinical settings for which invasive techniques are challenging to implement or do not characterize the biology of all tumors in a patient. Moreover, measuring MYC activity noninvasively opens the opportunity to study changes in MYC signaling in patients under targeted therapeutic conditions thought to indirectly inhibit MYC.
Bibliographical noteFunding Information:
S.C. Behr reports receiving other commercial research support from, has received speakers bureau honoraria from, and is a consultant/advisory board member for GE Healthcare. M.J. Evans reports receiving a commercial research grant from GE Healthcare and is a consultant/advisory board member for ORIC Pharmaceuticals, Inc. No potential conflicts of interest were disclosed by the other authors.
This research was supported by a Stand Up To Cancer - Prostate Cancer Foundation Prostate Dream Team Translational Research grant (SU2C-AACR-DT0812, principal investigator: E.J. Small). This research grant was made possible by the generous support of the Movember Foundation. M.J. Evans and R. Aggarwal are Young Investigator Awardees from the Prostate Cancer Foundation. M.J. Evans was supported by the NIH (R00CA172695, R01CA17661), a Department of Defense Idea Development Award (PC140107), the UCSF Academic Senate,andGEHealthcare.C.Truilletwassupportedbyapostdoctoralfellowship from the Department of Defense Prostate Cancer Research Program (PC151060). M.F.L.ParkerwassupportedbyapostdoctoralfellowshipfromtheDepartmentof Defense Prostate Cancer Research Program (PC161005). Research from UCSF reported in this publication was supported in part by the NCI of the NIH under award number P30CA082103.
© 2017 AACR.