# Quantitative In Vivo 68Ga-Fibroblast-Activation-Protein-Inhibitors (FAPI)-46 PET Imaging of Cancer-Associated Fibroblasts (CAFs) in Pancreatic Ductal Adenocarcinoma (PDA)

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $444,504

## Abstract

PROJECT SUMMARY
Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related deaths in the USA and is
anticipated to become the second leading cause by 2030. Its characteristic desmoplastic stroma, constituting
60–70% of its volume, is one of the critical factors that contributes to the dismal outcomes. Fibroblast activation
protein (FAP)-expressing Cancer-Associated Fibroblasts (CAFs) are one of the most important stromal
constituents because they play a fundamental role in the carcinogenesis, fibrosis, tumor growth, metastases,
and treatment resistance. FAP expression in PDA is an independent predictor of poor outcomes. Lack of
noninvasive tools to precisely profile CAF identity and function both temporally and spatially in vivo is a critical
barrier for translation of existing knowledge of the tumor microenvironment to address unmet clinical needs.
68Ga-FAP-inhibitor (FAPI)-46 has emerged as a PET radiotracer with optimal properties for FAP-targeted clinical
imaging and theranostics in PDA. These include low nanomolar affinity to FAP, near-complete internalization of
radioactivity bound to FAP, absence of physiologic uptake, rapid blood clearance and prolonged tumor retention,
and operational characteristics that offer tremendous flexibility to suit the clinical context, PET scanner profile,
and workflow for patients with PDA. Traditionally, long regulatory and reimbursement approval pathways coupled
with high costs of comparative studies have delayed clinical access to promising precision tools such as 68Ga-
FAPI-46 PET. Thus, for the clinical translation of a theranostic radiotracer such as 68Ga-FAPI-46, an academic-
industrial partnership (AIP) based on complementary strengths and a coherent clinical development strategy is
needed to reduce the risk and raise the likelihood of meeting FDA standards and consumer expectations. Our
AIP - Mayo Clinic and Sofie Biosciences (“SOFIE”) - will undertake a clinical investigation in compliance with
FDA standards to form the basis of a new drug application (NDA) with the goal to deliver a new capability to end
users, consistent with this FOA’s intent. Our hypothesis is that 68Ga-FAPI-46 PET will be an accurate technique
to detect and quantify CAFs and that metrics derived from 68Ga-FAPI-46 PET will be novel biomarkers in PDA.
In Aim 1, using immunophenotyping as the reference standard, the sensitivity and specificity of 68Ga-FAPI-46
PET will be evaluated for the detection and quantification of CAFs in PDA, along with inter-reader and intra-
reader reliability, and the dynamic changes in 68Ga-FAPI-46 PET biomarkers in response to neoadjuvant
treatment. In Aim 2, 68Ga-FAPI-46 PET will be compared, correlated, and combined with other mechanistically
distinct investigations to improve pre-surgical staging and to predict post-surgical outcomes. Our AIP has the
potential to deliver a noninvasive molecular imaging assay that can provide greater insight into disease biology,
impact clini...

## Key facts

- **NIH application ID:** 10907717
- **Project number:** 5R01CA272628-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Ajit Harishkumar Goenka
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $444,504
- **Award type:** 5
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907717

## Citation

> US National Institutes of Health, RePORTER application 10907717, Quantitative In Vivo 68Ga-Fibroblast-Activation-Protein-Inhibitors (FAPI)-46 PET Imaging of Cancer-Associated Fibroblasts (CAFs) in Pancreatic Ductal Adenocarcinoma (PDA) (5R01CA272628-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10907717. Licensed CC0.

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