PT  - JOURNAL ARTICLE
AU  - Joo Ho Tai
AU  - Binh Nguyen
AU  - R. Glenn Wells
AU  - Michael S. Kovacs
AU  - Rebecca McGirr
AU  - Frank S. Prato
AU  - Timothy G. Morgan
AU  - Savita Dhanvantari
TI  - Imaging of Gene Expression in Live Pancreatic Islet Cell Lines Using Dual-Isotope SPECT
AID  - 10.2967/jnumed.107.043430
DP  - 2008 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 94--102
VI  - 49
IP  - 1
4099  - http://jnm.snmjournals.org/content/49/1/94.short
4100  - http://jnm.snmjournals.org/content/49/1/94.full
SO  - J Nucl Med2008 Jan 01; 49
AB  - 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 αTC1-6 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) (αTC1-6 cells) or 123I-FIAU (INS-1 832/13 cells). For the first set of in vivo experiments, SPECT was conducted after αTC1-6/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: αTC1-6/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.