# Imaging Incipient Heart Failure by PET

> **NIH NIH F32** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $76,756

## Abstract

PROJECT SUMMARY
Heart failure represents a major cause of illness and mortality in the United States. Preemptive and preventative
care are the most effective methods for mitigating the severity of this disease. Thus, the early detection of heart
failure is critical to patient prognosis and overall cardiovascular health. The conventional methods for diagnosis
are limited to detection of significant cardiac damage and pathological remodeling. We propose using 2-
[18F]fluoropropionic acid ([18F]FPA) to image the metabolic alterations in fatty acid metabolism which precede
cardiac injury. [18F]FPA-PET is favorably suited for imaging these events and translation to the clinic as: 1)
[18F]FPA-PET has been used for imaging tumors in humans and accumulates in the heart, thereby confirming
its safety and favorable dosimetry, 2) short chain fatty acids, such as [18F]FPA, are preferentially taken up by the
injured heart in response to the impairment in long chain fatty acid oxidation, 3) propionic acid metabolism is
restricted to a single mitochondrial pathway which targets [18F]FPA to this organelle and limits its potential for
degradation. We predict the metabolic alterations that occur during heart failure effectively increase the uptake
and sequestration of [18F]FPA to the myocardium. The metabolic trapping of [18F]FPA is driven by acetyl-CoA
synthetase short chain family 1 (ACSS1), which converts these short chain fatty acids to metabolically active
and membrane impermeable CoA intermediates. ACSS1 expression and activity are upregulated in patients
experiencing heart failure, and many animal models of heart failure. Thus, we hypothesize that [18F]FPA
effectively accumulates in the injured heart and can be applied to image the early manifestations of cardiac
disease which precede irreversible cardiac injury and remodeling. The goals of this fellowship project are to 1)
determine if [18F]FPA can be used to image heart failure, and 2) investigate the role of ACSS1 in accounting for
the cardiac accumulation of [18F]FPA. The successful application of most imaging probes depends on a
comprehensive understanding of the biochemical pathways that these probes report on. In building our
understanding, we can develop precise applications for these tracers to image heart failure, as well as other
disease states. The long-term goals of this project will serve as a foundation for the applicant's independent
research career. These will be facilitated by the technical, conceptual, and practical knowledge that he will gain
over the course of the fellowship training.

## Key facts

- **NIH application ID:** 11061186
- **Project number:** 5F32HL168948-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Juan Arturo Azcona
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,756
- **Award type:** 5
- **Project period:** 2023-09-15 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11061186

## Citation

> US National Institutes of Health, RePORTER application 11061186, Imaging Incipient Heart Failure by PET (5F32HL168948-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11061186. Licensed CC0.

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