To investigate using a novel imaging approach – hyperpolarized (HP) C magnetic resonance imaging (MRI) for simultaneous metabolism and perfusion assessment – to evaluate early and does-dependent radiotherapy (RT) response in a prostate cancer mouse model.
Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice (n = 18) underwent single-fraction RT (4 – 14 Gy steep dose across the tumor) and were imaged serially at pre-RT baseline and 1, 4, and 7 days post-RT, using HP C MRI with combined [1-C]pyruvate (metabolic active agent) and [C]urea (perfusion agent), coupled with conventional multiparametric H MRI including T-weighted, dynamic contrast-enhanced (DCE), and diffusion-weighted imaging. Tumor tissues were collected at Day 4 and Day 7 for biological correlative studies.
We found a significant decrease in HP pyruvate-to-lactate conversion in tumors responding to RT, with concomitant significant increases in HP pyruvate-to-alanine conversion and HP urea signal; whereas the opposite changes were observed in tumors resistant to RT. Moreover, HP lactate change was radiation-dose dependent: tumor regions treated with higher radiation doses (10-14 Gy) exhibited a greater decrease in HP lactate signal than low-dose regions (4-7 Gy) as early as 1 day post-RT, consistent with LDH enzyme activity and expression data. We also found that HP [C]urea MRI provided similar assessments of tumor perfusion to those provided by H DCE MRI in this animal model. However, apparent diffusion coefficient (ADC), a conventional H MR functional biomarker, did not exhibit statistically significant changes within 7 days after RT.
These results demonstrate the ability of HP C MRI to monitor radiation-induced physiologic changes in a timely and dose-dependent manner, providing the basic science premise for further clinical investigations and translation.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.