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Research Papers

Multimodality imaging of T-cell hybridoma trafficking in collagen-induced arthritic mice: image-based estimation of the number of cells accumulating in mouse paws

[+] Author Affiliations
Shahriar S. Yaghoubi

Stanford University, Department of Radiology, Bio-X, Molecular Imaging Program, Stanford, California 94305-5427

Remi J. Creusot

Stanford University, Department of Medicine, Division of Immunology and Rheumatology, Stanford, California 94305-5427

Pritha Ray

Stanford University, Department of Radiology, Bio-X, Molecular Imaging Program, Stanford, California 94305-5427

C. Garrison Fathman

Stanford University, Department of Medicine, Division of Immunology and Rheumatology, Stanford, California 94305-5427

Sanjiv Sam Gambhir

Stanford University, Department of Radiology, Bio-X, Molecular Imaging Program and Department of Bioengineering, Stanford, California 94305-5427

J. Biomed. Opt. 12(6), 064025 (January 12, 2007July 20, 2007July 25, 2007December 28, 2007). doi:10.1117/1.2821415
History: Received January 12, 2007; Revised July 20, 2007; Accepted July 25, 2007; Published December 28, 2007
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Appropriate targeting of therapeutic cells is essential in adoptive cellular gene therapy (ACGT). Imaging cell trafficking in animal models and patients will guide development of ACGT protocols. Collagen type II (C-II)-specific T cell hybridomas are transduced with a lentivirus carrying a triple fusion reporter gene (TFR) construct consisting of a fluorescent reporter gene (RG), a bioluminescent RG (hRluc), and a positron emission tomography (PET) RG. Collagen-induced arthritic (CIA) mice are scanned with a bioluminescence imaging camera before and after implantation of various known cell quantities in their paws. Linear regression analysis yields equations relating two parameters of image signal intensity in mice paws to the quantity of hRluc expressing cells in the paws. Afterward, trafficking of intravenously injected cells is studied by quantitative analysis of bioluminescence images. Comparison of the average cell numbers does not demonstrate consistently higher accumulation of T-cell hybridomas in the paws with higher inflammation scores, and injecting more cells does not cause increased accumulation. MicroPET images illustrate above background signal in the inflamed paws and chest areas of CIA mice. The procedures described in this study can be used to derive equations for cells expressing other bioluminescent RGs and in other animal models.

Figures in this Article
© 2007 Society of Photo-Optical Instrumentation Engineers

Citation

Shahriar S. Yaghoubi ; Remi J. Creusot ; Pritha Ray ; C. Garrison Fathman and Sanjiv Sam Gambhir
"Multimodality imaging of T-cell hybridoma trafficking in collagen-induced arthritic mice: image-based estimation of the number of cells accumulating in mouse paws", J. Biomed. Opt. 12(6), 064025 (January 12, 2007July 20, 2007July 25, 2007December 28, 2007). ; http://dx.doi.org/10.1117/1.2821415


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