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

Date Published: November 30, 2009

Publisher: Public Library of Science

Author(s): Heling Zhou, Kate Luby-Phelps, Bruce E. Mickey, Amyn A. Habib, Ralph P. Mason, Dawen Zhao, Pedro Antonio Valdes-Sosa.

Abstract: 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.

Partial Text: Glioblastoma multiform (GBM) is a lethal intracranial cancer, which exhibits a relentless malignant progression and is highly resistant to conventional multimodal therapies. GBM is characterized by the nature of extensive infiltration into surrounding normal brain tissue, which results in incomplete tumor resection and consequent recurrence [1], [2]. It is imperative to improve diagnostic imaging to evaluate intracranial tumor growth and therapeutic responses. Optical imaging has been rapidly adapted to cancer research. Recently, optical imaging using fluorescent dye labeled tumor-specific molecules has been successfully applied to imaging glioma in preclinical animal models based on overexpression of such markers in glioma [3]–[5]. In the clinic, several recent studies have demonstrated the ability of fluorescence imaging to facilitate radical resection of GBM during surgery [6]–[8]. Promising results reported by Stummer, et al. have shown that gross total resection of glioma guided by intraoperative fluorescence imaging is associated with improved prognosis of the patients with a median survival of 15–18 months, compared to 10–12 months after a subtotal resection or about 6 months after biopsy alone [8].

Immunohistochemical study showed extensive expression of luciferase in the U87-luc cells of intracranial tumor tissues (Fig. 1A). Longitudinal BLI studies revealed a weak signal initially 11 days after tumor implantation, which became stronger on follow-up to day 24 (Fig. 1B). The mean light intensity detected on day 24 for the group of tumor bearing mice was significantly greater than on day 11 (16×107 versus 11×106 photons/s; p<0.05). MRI studies based on T2-weighted and T1-weighted contrast enhanced images confirmed an intracranial tumor located in the right side of the brain of each animal (Fig. 1C). A significant correlation was found between BLI signal and actual tumor volume measured by MRI (r = 0.8, p<0.05; Fig. 1D). Tumor volume determined on the last MRI scan (one day before the in vivo fluorescence imaging) varied from 42 to 136 mm3 in the seven animals. There was no significant difference in tumor volume between the group receiving the 2-DG dye or the control dye when the in vivo fluorescence imaging was performed (p = 0.5). We have demonstrated the feasibility of using the NIR dye labeled 2-deoxyglucose, IRDye800CW 2-DG, for in vivo fluorescence imaging of orthotopic glioma in a mouse model (Fig. 3). Ex vivo fluorescence imaging of tumor sections and microscopic imaging confirmed significantly higher accumulation of the 2-DG dye in intracranial tumors than in normal brain. Good correlations were found between each imaging modality in terms of in vivo evaluation of intracranial tumor burden (Figs. 1 and 4D). Source:


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