# A Molecular Imaging Approach to Immuno-Metabolic Characterization of Vessel Wall Macrophages

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $162,540

## Abstract

This proposal is a K08 Career Development Award application for Dr. Sina Tavakoli, an Assistant Professor
of Cardiothoracic Radiology at University of Pittsburgh. The candidate’s career goal is to become an independent
physician-scientist in the field of molecular imaging of cardiovascular diseases. The mentoring team consists of
Drs. Carolyn Anderson, PhD, Flordeliza Villanueva, MD, Prem Soman, MD, PhD, and Patrick Pagano, PhD,
who have an established history of mentoring successful physician-scientists. The proposal originates from the
candidate’s previous experience in metabolic divergence of macrophages upon activation into different
polarization states and its implications for imaging of vessel wall inflammation.
 Molecular imaging of inflammation has been extensively investigated to identify “vulnerable plaques”. Among
the various approaches, (18F-fluoro-deoxyglucose) 18F-FDG PET has been most commonly utilized in clinical
studies. However, the limited specificity of 18F-FDG, which targets a ubiquitous metabolic process, uncertainties
about its biological correlates, and its high myocardial uptake have been major barriers to its routine clinical use
in atherosclerosis. Recent ex vivo studies have shown that enhanced glutamine utilization is required for
polarization of macrophages into M2 (inflammation-resolving), but not M1 (pro-inflammatory), state and may
allow the distinction of inflammation-resolving from pro-inflammatory macrophages. Here, our central hypothesis
is that combined in vivo imaging of glutamine and glucose uptake allows for the characterization of immuno-
metabolic heterogeneity of macrophages in atherosclerosis and correlates with histological indices of plaque
vulnerability. We propose three Specific Aims:
 SPECIFIC AIM 1: To identify immuno-metabolic profiles of plaque macrophages and their association with
indices of vulnerability in a murine model of atherosclerosis.
 SPECIFIC AIM 2: To determine the potential of in vivo 18F-FDG and 18F-fluoroglutamine in characterizing
vessel wall inflammation and response to a novel anti-inflammatory intervention in murine atherosclerosis.
 SPECIFIC AIM 3: To determine the role of 18F-FGln and 18F-FDG PET in immunohistological and metabolic
characterization of human carotid endarterectomy specimens.
 The ultimate goals of the proposed experiments are: A) to address the biological relevance of 18F-FDG and
18F-FGln uptake by determining the in vivo immuno-metabolic profiles of macrophage subsets within the
microenvironment of plaques; and B) to explore the feasibility of quantitative in vivo 18F-FGln and 18F-FDG PET
in detection of metabolic heterogeneity of atherosclerotic plaques and monitoring the response to anti-
inflammatory interventions. The findings of this study may lead to improved plaque characterization, risk
stratification of patients, and monitoring the response to novel therapies. Considering the availability of 18F-FGln
for investigational use in oncological imaging,...

## Key facts

- **NIH application ID:** 10201736
- **Project number:** 5K08HL144911-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sina Tavakoli
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $162,540
- **Award type:** 5
- **Project period:** 2019-07-17 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201736

## Citation

> US National Institutes of Health, RePORTER application 10201736, A Molecular Imaging Approach to Immuno-Metabolic Characterization of Vessel Wall Macrophages (5K08HL144911-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201736. Licensed CC0.

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