Journal Article

Dynamic Near-Infrared Optical Imaging of 2-Deoxyglucose Uptake by Intracranial Glioma of Athymic Mice

Mickey, Bruce E., Mason, Ralph P., Zhao, Dawen, Habib, Amyn A., Zhou, Heling, Luby-Phelps, Kate

2009

Overview

It is recognized that cancer cells exhibit highly elevated glucose metabolism compared to non-tumor cells. We have applied in vivo optical imaging to study dynamic uptake of a near-infrared dye-labeled glucose analogue, 2-deoxyglucose (2-DG) by orthotopic glioma in a mouse model. The orthotopic glioma model was established by surgically implanting U87-luc glioma cells into the right caudal nuclear area of nude mice. Intracranial tumor growth was monitored longitudinally by bioluminescence imaging and MRI. When tumor size reached >4 mm diameter, dynamic fluorescence imaging was performed after an injection of the NIR labeled 2-DG, IRDye800CW 2-DG. Real-time whole body images acquired immediately after i.v. infusion clearly visualized the near-infrared dye circulating into various internal organs sequentially. Dynamic fluorescence imaging revealed significantly higher signal intensity in the tumor side of the brain than the contralateral normal brain 24 h after injection (tumor/normal ratio, TNR = 2.8+/-0.7). Even stronger contrast was achieved by removing the scalp (TNR = 3.7+/-1.1) and skull (TNR = 4.2+/-1.1) of the mice. In contrast, a control dye, IRDye800CW carboxylate, showed little difference (1.1+/-0.2). Ex vivo fluorescence imaging performed on ultrathin cryosections (20 microm) of tumor bearing whole brain revealed distinct tumor margins. Microscopic imaging identified cytoplasmic locations of the 2-DG dye in tumor cells. Our results suggest that the near-infrared dye labeled 2-DG may serve as a useful fluorescence imaging probe to noninvasively assess intracranial tumor burden in preclinical animal models.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Animals / Bioluminescence / Brain / Brain cancer / Brain Neoplasms - diagnosis / Brain Neoplasms - pathology / Brain tumors / Breast cancer / Cancer therapies / Cell Line, Tumor / Chemotherapy / Colorectal cancer / Comparative analysis / Deoxyglucose / Deoxyglucose - pharmacokinetics / Diagnostic imaging / Dyes / Epidermal growth factor / Fluorescence / Glioma / Glioma - diagnosis / Glioma - pathology / Glioma cells / Gliomas / Glucose / Glucose - metabolism / Humans / I.R. radiation / Image acquisition / In vivo methods and tests / Infrared imaging / Infusion / Injection / Luminescence / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Medical imaging / Medical prognosis / Metabolism / Metastasis / Mice / Mice, Inbred BALB C / Mice, Nude / Microscopy / Models, Biological / Neoplasm Transplantation / Neuroimaging / Oncology/Neuro-Oncology / Organs / Perfusion / Physiological aspects / Quantum dots / Radiology and Medical Imaging / Radiology and Medical Imaging/Magnetic Resonance Imaging / Rodents / Scalp / Studies / Surgical implants / Tumor cells / Tumors / Vascular endothelial growth factor