RAGE-specific single chain Fv for PET imaging of pancreatic cancer

Hye Yeong Kim, Xiaolei Wang, Rui Kang, Daolin Tang, Brian A. Boone, Herbert J. Zeh, Michael T. Lotze, W. Barry Edwards

Research output: Contribution to journalArticle

Abstract

Noninvasive detection of both early pancreatic neoplasia and metastases could enhance strategies to improve patient survival in this disease that is notorious for an extremely poor prognosis. There are almost no identifiable targets for non-invasive diagnosis by positron emission tomography (PET) for patients with pancreatic ductal adenocarcinoma (PDAC). Over-expression of the receptor for advanced glycation end products (RAGE) is found on the cell surface of both pre-neoplastic lesions and invasive PDAC. Here, a RAGE-specific single chain (scFv) was developed, specific for PET imaging in syngeneic mouse models of PDAC. An anti-RAGE scFv conjugated with a sulfo-Cy5 fluorescence molecule showed high affinity and selectivity for RAGE expressing pancreatic tumor cells and genetically engineered KRASG12D mouse models of PDAC. An in vivo biodistribution study was performed with the 64Cu-radiolabled scFv in a syngeneic murine pancreatic cancer model, demonstrating both the feasibility and potential of an anti-RAGE scFv for detection of PDAC. These studies hold great promise for translation into the clinic.

Original languageEnglish (US)
Article numbere0192821
JournalPloS one
Volume13
Issue number3
DOIs
StatePublished - Mar 2018
Externally publishedYes

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positron-emission tomography
pancreatic neoplasms
Single-Chain Antibodies
Positron emission tomography
adenocarcinoma
Pancreatic Neoplasms
Positron-Emission Tomography
Adenocarcinoma
image analysis
Imaging techniques
receptors
animal models
in vivo studies
metastasis
prognosis
Tumors
Neoplasms
Fluorescence
Cells
advanced glycation end products

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

RAGE-specific single chain Fv for PET imaging of pancreatic cancer. / Kim, Hye Yeong; Wang, Xiaolei; Kang, Rui; Tang, Daolin; Boone, Brian A.; Zeh, Herbert J.; Lotze, Michael T.; Barry Edwards, W.

In: PloS one, Vol. 13, No. 3, e0192821, 03.2018.

Research output: Contribution to journalArticle

Kim, Hye Yeong ; Wang, Xiaolei ; Kang, Rui ; Tang, Daolin ; Boone, Brian A. ; Zeh, Herbert J. ; Lotze, Michael T. ; Barry Edwards, W. / RAGE-specific single chain Fv for PET imaging of pancreatic cancer. In: PloS one. 2018 ; Vol. 13, No. 3.
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