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Research Articles: Therapeutics, Targets, and Development

Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging

¹ Department of Molecular Medicine, University of Texas Health Science Center at San Antonio; ² Molecular Therapeutics Division, Institute for Drug Development; ³ San Antonio Cancer Institute; ⁴ OsteoScreen Ltd., San Antonio, Texas; and ⁵ Cancer Biology, Amgen Washington, Seattle, Washington

Requests for reprints: Babatunde O. Oyajobi, Department of Cellular and Structural Biology (MSC 7762), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Phone: 210-567-0925; Fax: 1-210-567-3803. E-mail: oyajobi{at}uthscsa.edu

Abstract

Development of new therapies for myeloma has been hindered by the lack of suitable preclinical animal models of the disease in which widespread tumor foci in the skeleton can be detected reliably. Traditional means of detecting skeletal tumor infiltration such as histopathology are cumbersome and labor-intensive and do not allow temporal monitoring of tumor progression or regression in response to therapy. To resolve this problem, we modified the Radl 5TGM1 model of myeloma bone disease such that fluorescent myeloma tumors can be optically imaged in situ. Here, we show that murine myeloma 5TGM1 tumor cells, engineered to express enhanced green fluorescent protein (eGFP; 5TGM1-eGFP cells), can be imaged in a temporal fashion using a fluorescence illuminator and a charge-coupled device camera in skeletons of live C57BL/KaLwRij mice. High-resolution, whole-body images of tumor-bearing mice revealed that myeloma cells homed almost exclusively to the skeleton, with multiple focal tumor foci in the axial skeleton, consistent with myeloma tumor distribution in humans. Finally, the tested antitumor treatment effect of Velcade (bortezomib), a proteasome inhibitor used clinically in myeloma, was readily detected by GFP imaging, suggesting the power of the technique in combination with the Radl 5TGM1-eGFP model for rapid preclinical assessment and sensitive monitoring of novel and potential therapeutics. Whole-body GFP imaging is practical, convenient, inexpensive, and rapid, and these advantages should enable a high throughput when evaluating in vivo efficacy of new potential antimyeloma therapeutics and assessing response to treatment. [Mol Cancer Ther 2007;6(6):1701–8]

Grant support: NIH/National Cancer Institute grants KO1 CA104180 (B.O. Oyajobi) and PO1 CA40035 (G.R. Mundy) and an unrestricted research grant from Immunex Corporation (now Amgen Washington; to B.O. Oyajobi). The University of Texas Health Science Center at San Antonio flow cytometry facility is supported by Cancer Center Grant P30 CA054174 to the San Antonio Cancer Institute.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Note: Present address for B.O. Oyajobi: Department of Cellular & Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900; Present address for R. Kakonen: Pharmatest Services Ltd., 20520 Turku, Finland; Present address for G.R. Mundy: Department of Medicine, Vanderbilt Center for Bone Biology, Vanderbilt, University Medical Center, Nashville, TN 37232-0575.

Received 2/22/07; accepted 4/27/07.

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