# Peptide-based targeted molecular imaging for early detection in pancreatic cancer

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $632,421

## Abstract

One of the major challenges of pancreatic ductal adenocarcinoma (PDAC) is the identification,
development and validation of novel molecular markers and imaging probes that would enable earlier detection
and provide a rational guide for treatment regimens. We are proposing the integrin subtype αvβ6 as a novel
molecular imaging marker for further development and validation combined with a non-invasive peptide-based
molecular imaging strategy for in vivo detection of disease progression. αvβ6 is an epithelial-specific cell
surface receptor that is undetectable in healthy adult epithelium but is significantly upregulated in a wide range
of epithelial derived cancers. This receptor is often localized to the invasive front of tumors and plays a key role
in invasion and metastasis. αvβ6 was initially identified in pancreatic cancer with the majority of human
PDAC samples tested receiving the maximum score from IHC. The PI has developed an αvβ6-directed
molecular imaging agent, 18F-αvβ6-binding-peptide (18F-αvβ6-BP), which has high affinity and selectivity for αvβ6
integrin and demonstrated favorable pharmacokinetics in tumor-bearing mice and non-human-primates.
Approval to proceed with a first-in-human study was recently granted by the FDA.
 The overall goal of this U01 is to validate αvβ6 integrin as a non-invasive molecular imaging target for
the early detection of PDAC with PET using 18F-αvβ6-BP. Our three Aims will run in parallel over this five year
proposal. In Aim 1 a) we will evaluate αvβ6 expression in human pancreatic tissue (IPMN, MCN and PDAC),
and b) we will evaluate αvβ6 expression non-invasively in murine pancreatic cancer progression models of
IPMN or MCN to PDAC using small animal PET imaging to determine if αvβ6 is a useful marker to evaluate
progression of neoplastic transformation. In Aim 2 we will perform a human prospective cohort study evaluating
αvβ6 imaging. Patient with suspect PDAC and cystic pancreatic lesions (IPMN or MCN) will get standard of
care (SOC) treatment, molecular analysis of the aspirate and 18F-αvβ6-BP-PET/CT. We will compare a) SOC
and molecular testing with 18F-αvβ6-BP-PET/CT imaging in risk stratification and b) 18F-αvβ6-BP-PET/CT
imaging with resected specimen pathology. In Aim 3 we will develop a multiplexed targeting strategy to
interrogate two molecular markers simultaneously in vivo. We have selected αvβ6 and Plectin-1 as our initial
model as both targets have been identified in PDAC and peptide-based targeted molecular imaging agents
already exist for each target.
 This targeted molecular imaging approach facilitates personalized medicine, with αvβ6-directed
imaging identifying high-risk precursor lesions for intervention while sparing low risk lesions unnecessary
intervention. The team assembled has significant expertise and resources in molecular probe development and
small-animal molecular imaging that can be leveraged by the Pancreatic Cancer Detection Consortium for
rapid validation of future molec...

## Key facts

- **NIH application ID:** 9987310
- **Project number:** 5U01CA217665-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** JULIE L SUTCLIFFE
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $632,421
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9987310

## Citation

> US National Institutes of Health, RePORTER application 9987310, Peptide-based targeted molecular imaging for early detection in pancreatic cancer (5U01CA217665-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9987310. Licensed CC0.

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