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Real-Time Transferrin-Based PET Detects MYC-Positive Prostate Cancer

Authors :
Eric J. Small
Emily Chang
Pamela L. Paris
Charles J. Ryan
Junnian Wei
Spencer C. Behr
Gayatri Premasekharan
Loc T. Huynh
Rahul Aggarwal
Michael J. Evans
Kenneth T. Gao
Nimna Ranatunga
Jack F. Youngren
Byron Hann
Jiaoti Huang
Matthew F.L. Parker
Charles Truillet
Source :
Molecular cancer research : MCR, vol 15, iss 9
Publication Year :
2017
Publisher :
eScholarship, University of California, 2017.

Abstract

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. Mol Cancer Res; 15(9); 1221–9. ©2017 AACR.

Details

Database :
OpenAIRE
Journal :
Molecular cancer research : MCR, vol 15, iss 9
Accession number :
edsair.doi.dedup.....f27793d67adc128f42df2955d134837d