TSPO-targeted PET and optical probes for the detection and localization of premalignant and malignant pancreatic lesions

Allison S. Cohen, Jun Li, Matthew R. Hight, Eliot McKinley, Allie Fu, Adria Payne, Yang Liu, Dawei Zhang, Qing Xie, Mingfeng Bai, Gregory D. Ayers, Mohammed Noor Tantawy, Jarrod A. Smith, Frank Revetta, M. Kay Washington, Chanjuan Shi, Nipun Merchant, H. Charles Manning

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Purpose: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic “incidentalomas,” particularly cysts, are frequently identified in asymptomatic patients through anatomic imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions. Experimental Design: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in premalignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted PET agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-IR optical imaging based upon the V-1008 pharmacophore, was developed and evaluated. Results: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, premalignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to premalignant pancreatic lesions and advanced tumors enabling real-time IGS. Conclusions: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.

Original languageEnglish (US)
Pages (from-to)5914-5925
Number of pages12
JournalClinical Cancer Research
Volume26
Issue number22
DOIs
StatePublished - Nov 15 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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