Abstract
Islet transplantation is an attractive approach for treating type-1 diabetes, but there is a massive loss of transplanted islets. It is currently only possible to estimate islet mass indirectly, through measurement of circulating C-peptide and insulin levels. This type of estimation, however, is not sufficiently sensitive or reproducible for follow-up of individuals who have undergone islet transplantation. Here we show that islet graft survival could be assessed for 1 month in diabetic NOD mice using 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG)–positron emission tomography (PET) technology, the PET signal reflecting insulin secretory capacity of transplanted islets. Expression of the gene encoding viral interleukin-10 (vIL-10), was measurable in real time with PET scanning. Additionally, we addressed the clinical potential of this approach by visualizing transplanted islets in the liver, the preferred clinical transplantation site. We conclude that quantitative in vivo PET imaging is a valid method for facilitating the development of protocols for prolonging islet survival, with the potential for tracking human transplants.
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Acknowledgements
We would like to thank V. Sossi for assistance with data reconstruction, M.J. Adam for advice on [18F]FHBG radiosynthesis, S. McCormick and M. Speck for technical assistance, and M.E. Black (Washington State University) for antibody to HSV1-sr39TK. These studies were supported by funding to C.H.S.M. from the Canadian Institutes of Health Research (#590007) and the Canadian Foundation for Innovation.
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Supplementary information
Supplementary Fig. 1
Imunohistochemical staining of the left and right kidneys. (PDF 46 kb)
Supplementary Fig. 2
Imunohistochemical staining of islet transplanted kidneys. (PDF 92 kb)
Supplementary Fig. 3
The presence of DNA encoding vIL-10 in rAD-vIL10-ITK treated islet transplanted kidneys and plasma vIL-10 levels. (PDF 37 kb)
Supplementary Fig. 4
Cell viability on treatment with FHBG. Islets isolated from male C57BL/6 mice were infected with 250 m.o.i. of rAD-TK. (PDF 17 kb)
Supplementary Video 1
1 h-time course PET imaging of islets transplanted under the kidney capsule of C57 BL/6 mouse. (MOV 742 kb)
Supplementary Video 2
1 h-time course PET imaging of islet transplanted into the liver of C57 BL/6 mouse. (MOV 814 kb)
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Kim, SJ., Doudet, D., Studenov, A. et al. Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat Med 12, 1423–1428 (2006). https://doi.org/10.1038/nm1458
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DOI: https://doi.org/10.1038/nm1458
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