# The Development of Radiolabeled Positional isomers of [11C]Pyruvate for Imaging Cancer Metabolism

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $251,397

## Abstract

The objectives of screening and diagnostic strategies in cancer are to detect disease within the window
of curability and avoid over- and under-treatment. The discovery of imaging biomarkers that improve the
identification of aggressive versus non-aggressive variants of disease would enhance our ability to treat patients
appropriately. In contrast to normal cells, cancer cells typically reduce pyruvate to lactate, a phenomenon known
as the Warburg effect. This altered metabolism provides an opportunity to distinguish tumors from healthy tissue
by non-invasive molecular imaging. Increased demand for glucose by metabolically reprogrammed cancer cells
is exploited by positron emission tomography (PET) imaging using [18F]fluorodeoxyglucose, [18F]FDG, which
typically delineates tumors with high sensitivity. Prostate cancer (PCa), however, does not typically exhibit the
Warburg effect, and [18F]FDG uptake in PCa is low. Alternative biomarkers to [18F]FDG would be valuable tools
with which to diagnose and stage PCa, the most frequently diagnosed cancer in men in the US. As PCa develops
resistance to therapies that block androgen receptor (AR) signaling, it transitions to a glycolytic phenotype
characterized by reduction of pyruvate to lactate. Pyruvate is at the nexus of cellular metabolism, and is therefore
an attractive candidate for imaging cancer metabolism by PET. Carbon-11-labeled pyruvate couples the
advantages of PET, including enhanced sensitivity and biochemical resolution, to an essential metabolite whose
specific metabolic fate has important implications for disease staging and prognosis, monitoring therapy, and
identifying new therapeutic targets. We propose to label pyruvate with carbon-11 at either the C-1 position ([1-
11C]pyruvate) or the C-3 position ([3-11C]pyruvate). By labeling this simple molecule at different positions, it will
be possible to infer the metabolic fate of pyruvate and therefore determine the aggressiveness of PCa tumors.
Current syntheses of these molecules are inadequate for imaging needs. The automated synthesis of [1-11C]-
and [3-11C]pyruvate via D-[11C]alanine is the first aim of this proposal. We will evaluate [1-11C]- and [3-
11C]pyruvate flux in two preclinical xenograft models of PCa: androgen-sensitive LNCaP, which we expect to
predominantly oxidize pyruvate to acetyl-CoA and CO2, and androgen-insensitive, N-Myc overexpressing PC3,
which we expect to predominantly reduce pyruvate to lactate. We hypothesize that the clearance of radioactivity
from LNCaP tumors will be significantly faster following administration of [1-11C]pyruvate than following
administration of [3-11C]pyruvate. By contrast, we expect the clearance rates to be similar in PC3 tumors. Finally,
we will exploit known metabolic differences in PCa cell lines to measure the metabolic fate of pyruvate in the
presence or absence of androgens. Our expectation is that aggressiveness and AR signaling blockade will be
associated with elevated levels of...

## Key facts

- **NIH application ID:** 10057979
- **Project number:** 1R21EB029649-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** James Kelly
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,397
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057979

## Citation

> US National Institutes of Health, RePORTER application 10057979, The Development of Radiolabeled Positional isomers of [11C]Pyruvate for Imaging Cancer Metabolism (1R21EB029649-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057979. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*