Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer

Synthesis and Evaluation in Vitro and in Vivo

Allison S. Cohen, Renata Patek, Steven A. Enkemann, Joseph O. Johnson, Tingan Chen, Eric Toloza, Josef Vagner, David L. Morse

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In the United States, lung cancer is the leading cause of cancer death and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta-opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung. Thus, we decided to develop a lung cancer-specific imaging agent targeting this receptor. We have previously developed a δOR-targeted fluorescent imaging agent based on a synthetic peptide antagonist (Dmt-Tic) conjugated to a Cy5 fluorescent dye. In this work, we describe the synthesis of Dmt-Tic conjugated to a longer wavelength near-infrared fluorescent (NIRF) dye, Li-cor IR800CW. Binding affinity of Dmt-Tic-IR800 for the δOR was studied using lanthanide time-resolved fluorescence (LTRF) competitive binding assays in cells engineered to overexpress the δOR. In addition, we identified lung cancer cell lines with high and low endogenous expression of the δOR. We confirmed protein expression in these cell lines using confocal fluorescence microscopy imaging and used this technique to estimate the cell-surface receptor number in the endogenously expressing lung cancer cell lines. The selectivity of Dmt-Tic-IR800 for imaging of the δOR in vivo was shown using both engineered cell lines and endogenously expressing lung cancer cells in subcutaneous xenograft models in mice. In conclusion, the δOR-specific fluorescent probe developed in this study displays excellent potential for imaging of lung cancer.

Original languageEnglish (US)
Pages (from-to)427-438
Number of pages12
JournalBioconjugate Chemistry
Volume27
Issue number2
DOIs
StatePublished - Feb 17 2016

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delta Opioid Receptor
Opioid Receptors
Fluorescent Dyes
Lung Neoplasms
Cells
Infrared radiation
Imaging techniques
Cell Line
Dyes
Confocal microscopy
Fluorescence microscopy
Lanthanoid Series Elements
Rare earth elements
Peptides
Cell Surface Receptors
Competitive Binding
Assays
Heterografts
Optical Imaging
Fluorescence

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Organic Chemistry
  • Pharmaceutical Science
  • Biomedical Engineering
  • Pharmacology

Cite this

Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer : Synthesis and Evaluation in Vitro and in Vivo. / Cohen, Allison S.; Patek, Renata; Enkemann, Steven A.; Johnson, Joseph O.; Chen, Tingan; Toloza, Eric; Vagner, Josef; Morse, David L.

In: Bioconjugate Chemistry, Vol. 27, No. 2, 17.02.2016, p. 427-438.

Research output: Contribution to journalArticle

Cohen, Allison S. ; Patek, Renata ; Enkemann, Steven A. ; Johnson, Joseph O. ; Chen, Tingan ; Toloza, Eric ; Vagner, Josef ; Morse, David L. / Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer : Synthesis and Evaluation in Vitro and in Vivo. In: Bioconjugate Chemistry. 2016 ; Vol. 27, No. 2. pp. 427-438.
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