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ACS Chem Neurosci. 2018 Jan 17;9(1):100-106. doi: 10.1021/acschemneuro.7b00111. Epub 2017 Jun 5.

Biotinylated Bioluminescent Probe for Long Lasting Targeted in Vivo Imaging of Xenografted Brain Tumors in Mice.

Author information

1
Department of Cell and Molecular Pharmacology & Experimental Therapeutics, §Neurosciences, ‡Hollings Cancer Center, Medical University of South Carolina , Charleston, South Carolina 29425, United States.

Abstract

Bioluminescence is a useful tool for imaging of cancer in in vivo animal models that endogenously express luciferase, an enzyme that requires a substrate for visual readout. Current bioluminescence imaging, using commonly available luciferin substrates, only lasts a short time (15-20 min). To avoid repeated administration of luciferase substrate during cancer detection and surgery, a long lasting bioluminescence imaging substrate or system is needed. A novel water-soluble biotinylated luciferase probe, B-YL (1), was synthesized. A receptor-targeted complex of B-YL with streptavidin (SA) together with a biotinylated epidermal growth factor short peptide (B-EGF) (SA/B-YL/B-EGF = 1:3:1, molar ratio) was then prepared to demonstrate selective targeting. The complex was incubated with brain cancer cell lines overexpressing the EGF receptor (EGFR) and transfected with the luciferase gene. Results show that the complex specifically detects cancer cells by bioluminescence. The complex was further used to image xenograft brain tumors transfected with a luciferase gene in mice. The complex detects the tumor immediately, and bioluminescence lasts for 5 days. Thus, the complex generates a long lasting bioluminescence for cancer detection in mice. The complex with selective targeting may be used in noninvasive cancer diagnosis and accurate surgery in cancer treatment in clinics in the future.

KEYWORDS:

Glioblastoma; bioluminescence; epidermal growth factor; in vivo imaging

PMID:
28532151
PMCID:
PMC5947857
DOI:
10.1021/acschemneuro.7b00111
[Indexed for MEDLINE]
Free PMC Article

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