# Multimodal quantitative PET/MR imaging of pulmonary fibrosis

> **NIH NIH K01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $157,680

## Abstract

Project Summary/Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a devastatingly progressive disease with median survival of 2-4 years
post diagnosis. Three decades of research and over 20 clinical trials have resulted in only two approved
treatments for IPF: pirfenidone and nintedanib. While both drugs slow disease progression, there are
differences in treatment response for individual IPF patients and neither drug is curative suggesting that IPF
may arise from different pathologic pathways resulting in disease heterogeneity. Drug development in IPF is
hampered by poor patient phenotyping and a lack of tools to assess disease activity and early treatment
response. As a result, clinical trials require large numbers of subjects to observe real efficacy signals.
Multimodal molecular imaging offers to accelerate drug development and ultimately change IPF management.
Molecular imaging of specific targets can stratify subjects, assess drug-target engagement and guide dose
optimization for a new drug designed to bind to that target. Molecular imaging also can assess disease activity
and monitor response to therapy. A comprehensive multimodal molecular imaging protocol would thus improve
the probability for clinical trial success with smaller patient numbers in a shorter period of time.
We propose to use multimodal imaging of αvβ3 integrin and oxidized collagen in mouse models of lung fibrosis
to evaluate αvβ3 antagonism as a route to pathway-specific intervention. αvβ3 is implicated as a regulator of
IPF development with αvβ3 expression elevated in preclinical models and in the lungs of IPF patients.
Treatment with αvβ3 antagonists leads to reduction of lung fibrosis and enhanced survival in preclinical models
of pulmonary fibrosis and several antagonists are entering clinical trials for IPF. The positron emission
tomography (PET) probe 18F-FPP-RGD2 was used to image αvβ3 in (pre-)clinical studies of cancer. To assess
disease activity, we’ve developed the allysine-binding magnetic resonance (MR) probe Gd-CHyd which reports
on the oxidized collagen formed during fibrogenesis. We showed that imaging oxidized collagen predicts
disease activity and treatment response. Because oxidized collagen is fundamental to fibrogenesis, Gd-CHyd
can quantify pulmonary disease activity independent of cause and can be used generally to measure response
to treatment. We will develop and optimize a multimodal 18F-FPP-RGD2 PET and Gd-CHyd MR imaging
protocol in mouse models of pulmonary fibrosis, then use this to noninvasively quantify αvβ3 expression and
fibrogenesis through the course of disease progression with validation by ex vivo measurements. We will then
apply the protocol to confirm target engagement of an αvβ3 antagonist, determine optimal therapeutic dose,
and use Gd-CHyd MR to measure therapeutic response. We hypothesize that molecular imaging will allow pre-
clinical assessment of target relevance while simultaneously assessing disease activity and response to t...

## Key facts

- **NIH application ID:** 10904731
- **Project number:** 5K01HL155237-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Eman Akam-Baxter
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $157,680
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904731

## Citation

> US National Institutes of Health, RePORTER application 10904731, Multimodal quantitative PET/MR imaging of pulmonary fibrosis (5K01HL155237-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10904731. Licensed CC0.

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