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

Hecong Qin; Vickie Zhang; Robert A Bok; Romelyn Delos Santos; J Adam Cunha; I-Chow Hsu; Justin Delos Santos Bs; Jessie E Lee; Subramaniam Sukumar; Peder E Z Larson; Daniel B Vigneron; David M Wilson; Renuka Sriram; John Kurhanewicz

doi:10.1016/j.ijrobp.2020.04.022

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

Int J Radiat Oncol Biol Phys. 2020 Aug 1;107(5):887-896. doi: 10.1016/j.ijrobp.2020.04.022. Epub 2020 Apr 25.

Affiliations

¹ Department of Radiology and Biomedical Imaging, University of California, San Francisco, California; Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, California.
² Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
³ Department of Radiation Oncology, University of California, San Francisco, California.
⁴ Department of Radiology and Biomedical Imaging, University of California, San Francisco, California; Graduate Program in Bioengineering, University of California, Berkeley and University of California, San Francisco, California. Electronic address: john.kurhanewicz@ucsf.edu.

Abstract

Purpose: 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.

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 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.

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 [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.

Conclusion: 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carbon Isotopes
Disease Models, Animal
Dose-Response Relationship, Radiation
Magnetic Resonance Imaging*
Male
Mice
Perfusion Imaging*
Prostatic Neoplasms / blood supply
Prostatic Neoplasms / diagnostic imaging*
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / radiotherapy*
Pyruvic Acid
Time Factors
Treatment Outcome
Urea

Substances

Carbon Isotopes
Pyruvic Acid
Urea
Carbon-13