Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions.

Publication ,  Journal Article
Cohen, AS; Li, J; Hight, MR; McKinley, E; Fu, A; Payne, A; Liu, Y; Zhang, D; Xie, Q; Bai, M; Ayers, GD; Tantawy, MN; Smith, JA; Revetta, F ...
Published in: Clin Cancer Res
November 15, 2020

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

November 15, 2020

Volume

26

Issue

22

Start / End Page

5914 / 5925

Location

United States

Related Subject Headings

  • Receptors, GABA
  • Precancerous Conditions
  • Pancreatic Neoplasms
  • Pancreatic Cyst
  • Pancreas
  • Oncology & Carcinogenesis
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Cholesterol
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cohen, A. S., Li, J., Hight, M. R., McKinley, E., Fu, A., Payne, A., … Manning, H. C. (2020). TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions. Clin Cancer Res, 26(22), 5914–5925. https://doi.org/10.1158/1078-0432.CCR-20-1214
Cohen, Allison S., Jun Li, Matthew R. Hight, Eliot McKinley, Allie Fu, Adria Payne, Yang Liu, et al. “TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions.Clin Cancer Res 26, no. 22 (November 15, 2020): 5914–25. https://doi.org/10.1158/1078-0432.CCR-20-1214.
Cohen AS, Li J, Hight MR, McKinley E, Fu A, Payne A, et al. TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions. Clin Cancer Res. 2020 Nov 15;26(22):5914–25.
Cohen, Allison S., et al. “TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions.Clin Cancer Res, vol. 26, no. 22, Nov. 2020, pp. 5914–25. Pubmed, doi:10.1158/1078-0432.CCR-20-1214.
Cohen AS, Li J, Hight MR, McKinley E, Fu A, Payne A, Liu Y, Zhang D, Xie Q, Bai M, Ayers GD, Tantawy MN, Smith JA, Revetta F, Washington MK, Shi C, Merchant N, Manning HC. TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions. Clin Cancer Res. 2020 Nov 15;26(22):5914–5925.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

November 15, 2020

Volume

26

Issue

22

Start / End Page

5914 / 5925

Location

United States

Related Subject Headings

  • Receptors, GABA
  • Precancerous Conditions
  • Pancreatic Neoplasms
  • Pancreatic Cyst
  • Pancreas
  • Oncology & Carcinogenesis
  • Mice
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Cholesterol