Work

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

Year: 2020

Type: article

Abstract: Purpose To investigate use of a novel imaging approach, hyperpolarized (HP) 13 C 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. Methods and Materials 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 13 C MRI with combined [1- 13 C]pyruvate (metabolic active agent) and [ 13 C]urea (perfusion agent), coupled with conventional multiparametric 1 H 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. Results 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 [ 13 C]urea MRI provided assessments of tumor perfusion similar to those provided by 1 H dynamic contrast-enhanced MRI in this animal model. However, apparent diffusion coefficien , a conventional 1 H MRI functional biomarker, did not exhibit statistically significant changes within 7 days after RT. Conclusion These results demonstrate the ability of HP 13 C 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.

Source: International Journal of Radiation Oncology*Biology*Physics

DOI: 10.1016/j.ijrobp.2020.04.022