Simultaneous Metabolic and Perfusion Imaging Using Hyperpolarized ¹³C MRI Can Evaluate Early and Dose-Dependent Response to Radiation Therapy in a Prostate Cancer Mouse Model.

Abstract

To investigate use of a novel imaging approach, hyperpolarized (HP) ¹³C magnetic resonance imaging (MRI) for simultaneous metabolism and perfusion assessment, to evaluate early and dose-dependent response to radiation therapy (RT) 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 after RT using HP ¹³C MRI with combined [1-¹³C]pyruvate (metabolic active agent) and [¹³C]urea (perfusion agent), coupled with conventional multiparametric ¹H MRI including T2-weighted, dynamic contrast-enhanced, and diffusion-weighted imaging. Tumor tissues were collected 4 and 7 days after RT 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; the opposite changes were observed in tumors resistant to RT. Moreover, HP lactate change was dependent on radiation dose; 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 lactate dehydrogenase enzyme activity and expression data. We also found that HP [¹³C]urea MRI provided assessments of tumor perfusion similar to those provided by ¹H dynamic contrast-enhanced MRI in this animal model. However, apparent diffusion coefficien , a conventional ¹H MRI functional biomarker, did not exhibit statistically significant changes within 7 days after RT. These results demonstrate the ability of HP ¹³C MRI to monitor radiation-induced physiologic changes in a timely and dose-dependent manner, providing the basic science premise for further clinical investigation and translation.