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Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT

¹ Lawson Health Research Institute, London, Ontario, Canada; ² University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and ³ Preclinical Imaging, GE Health Care–Biosciences, London, Ontario, Canada

Correspondence: For correspondence or reprints contact: Savita Dhanvantari, PhD, Lawson Health Research Institute, 268 Grosvenor St., London, Ontario N6A 4V2, Canada. E-mail: sdhanvan{at}uwo.ca

We are combining nuclear medicine with molecular biology to establish a sensitive, quantitative, and tomographic method with which to detect gene expression in pancreatic islet cells in vivo. Dual-isotope SPECT can be used to image multiple molecular events simultaneously, and coregistration of SPECT and CT images enables visualization of reporter gene expression in the correct anatomic context. We have engineered pancreatic islet cell lines for imaging with SPECT/CT after transplantation under the kidney capsule. Methods: INS-1 832/13 and TC1-6 cells were stably transfected with a herpes simplex virus type 1–thymidine kinase–green fluoresecent protein (HSV1-thymidine kinase-GFP) fusion construct (tkgfp). After clonal selection, radiolabel uptake was determined by incubation with 5-¹³¹I-iodo-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil (¹³¹I-FIAU) (TC1-6 cells) or ¹²³I-FIAU (INS-1 832/13 cells). For the first set of in vivo experiments, SPECT was conducted after TC1-6/tkgfp cells had been labeled with either ¹³¹I-FIAU or ¹¹¹In-tropolone and transplanted under the left kidney capsule of CD1 mice. Reconstructed SPECT images were coregistered to CT. In a second study using simultaneous acquisition dual-isotope SPECT, INS-1 832/13 clone 9 cells were labeled with ¹¹¹In-tropolone before transplantation. Mice were then systemically administered ¹²³I-FIAU and data for both ¹³¹I and ¹¹¹In were acquired simultaneously. Results: TC1-6/tkgfp cells showed a 15-fold greater uptake of ¹³¹I-FIAU, and INS-1/tkgfp cells showed a 12-fold greater uptake of ¹²³I-FIAU, compared with that of wild-type cells. After transplantation under the kidney capsule, both reporter gene expression and location of cells could be visualized in vivo with dual-isotope SPECT. Immunohistochemistry confirmed the presence of glucagon- and insulin-positive cells at the site of transplantation. Conclusion: Dual-isotope SPECT is a promising method to detect gene expression in and location of transplanted pancreatic cells in vivo.

Key Words: gene expression • pancreatic islet cell transplantation • diabetes • dual-isotope SPECT

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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