Preclinical Fluorescence-Guided Imaging Leveraging Surrounding Sentinel Tumor Microenvironment Identifies High-Risk Premalignant Pancreatic Lesions

Authors

Shilpa Sharma
Xiaoxia Wen
Jianbo Wang
Beibei Huang
Denise A Hernandez
Cong-Dat Pham
Zhiwen Liu
Susanne Je-Han Lin
Aiko Yamaguchi
Dimitra K Georgiou
Ryan P Coll
H Charles Manning

Language

English

Publication Date

11-3-2025

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-25-1092

PMID

40853902

PMCID

PMC12444433

PubMedCentral® Posted Date

9-19-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Purpose: Because surgery is the only potential cure for pancreatic cancer, high-risk premalignant pancreatic lesions often evade detection by palpation or white-light visualization, increasing the risk of recurrence. We asked whether near-infrared fluorescence imaging of tumor-associated inflammation could identify high-risk premalignant lesions, leveraging the tumor microenvironment as a sentinel of local disease and, thus, enhance surgery outcomes.

Experimental design: Fluorescence-guided surgery was performed on genetically engineered mice [Ptf1a-Cre; LSL-KrasG12D/+; Smad4flox/flox (KSC)] at discrete stages of disease progression, histologically confirmed high-risk, premalignant lesions in postnatal mice to locally advanced pancreatic tumors in adults, using the imaging agent V-1520, a translocator protein ligand. Age-matched wild-type littermates were used as controls, whereas Ptf1a-Cre; LSL-KrasG12D/+ mice modeled pancreatitis and precursors of low penetrance. Localization of V-1520 and tumor-associated macrophages among the tumor microenvironment was detected by immunofluorescence imaging.

Results: V-1520 exhibited robust accumulation in the pancreata of KSC mice from the early postnatal stage. Increased accumulation was observed in the pancreata of adolescent- and adult-aged mice with greater ductal lesion and stromal burden. Confocal microscopy of ex vivo pancreas specimens co-localized V-1520 accumulation primarily with CD68-expressing macrophages in KSC mice. Unlike the pancreata of KSC mice, accumulation of V-1520 did not exceed background levels in the pancreata of Ptf1a-Cre; LSL-KrasG12D/+ mice with pancreatitis.

Conclusions: V-1520 exhibited differential accumulation in pancreatic cancer-associated inflammation compared with pancreatitis. Given the robust tracer uptake in tissues associated with early yet high-risk lesions, we envision that V-1520 could enhance surgical resection and reduce the potential for recurrence from residual disease.

Keywords

Animals, Tumor Microenvironment, Mice, Pancreatic Neoplasms, Precancerous Conditions, Humans, Disease Models, Animal, Optical Imaging, Mice, Transgenic, Female

Published Open-Access

yes

Recommended Citation

Sharma, Shilpa; Wen, Xiaoxia; Wang, Jianbo; et al., "Preclinical Fluorescence-Guided Imaging Leveraging Surrounding Sentinel Tumor Microenvironment Identifies High-Risk Premalignant Pancreatic Lesions" (2025). Faculty, Staff and Student Publications. 6234.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6234