# Application of hyperpolarized 13C interstitial pH imaging to risk stratification in prostate cancer

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $157,091

## Abstract

PROJECT SUMMARY
The central aim of this proposal is to apply a method for high resolution imaging of interstitial pH using
hyperpolarized 13C magnetic resonance imaging to the detection of aggressive, potentially lethal disease in
prostate cancer. We have very recently developed a method for production of a highly concentrated and
polarized solution of hyperpolarized 13C bicarbonate through polarization of a precursor, glycerol carbonate,
and subsequent hydrolysis. This method overcomes many of the limitations of previously described pH
imaging methods and has a strong potential to allow for clinical translation. Prostate cancer presents with a
heterogeneous disease course, and there is an urgent unmet clinical need for improved biomarkers for the
detection or exclusion of aggressive, potentially lethal disease. One potential prognostic imaging biomarker in
prostate cancer is acidic interstitial pH, which is associated with local invasion and metastases in animal
models in a variety of cancers. Thus, a high resolution, clinically translatable method of imaging interstitial pH
would have significant impact and could find immediate utility in initial staging of men with low or intermediate
risk prostate cancer.
The goal of this proposal is to test the ability of a recently developed hyperpolarized 13C magnetic
resonance imaging method targeting interstitial acidity to predict high grade disease and subsequent
progression in murine models of prostate cancer, and to develop suitable production and quality
control methods for subsequent clinical translation. In specific aim 1, the correlation between interstitial
acidity, high grade disease, and disease progression is studied in the transgenic adenocarcinoma of the
prostate (TRAMP) animal model. In specific aim 2, this correlation is further validated in new, more clinically
relevant models of prostate cancer, and the fundamental molecular mechanisms underpinning interstitial
acidity are studied through pharmacologic modulation of various pathways. In specific aim 3, the production
and imaging methods are optimized and suitable quality control measures are generated for subsequent
clinical translation. If completed, the experiments outlined in this proposal would cement interstitial acidity as
an imaging biomarker for aggressive, potentially lethal prostate cancer in animal models, elucidate molecular
mechanisms underlying the phenomenon, and set the stage for subsequent clinical translation in men with
prostate cancer.

## Key facts

- **NIH application ID:** 9888209
- **Project number:** 5R21EB026012-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Robert Richard Flavell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,091
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9888209

## Citation

> US National Institutes of Health, RePORTER application 9888209, Application of hyperpolarized 13C interstitial pH imaging to risk stratification in prostate cancer (5R21EB026012-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9888209. Licensed CC0.

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