Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival.
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-[(18)F]-fluoro-3-hydroxymethylbutyl)guanine ([(18)F]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.
Kim
Su-Jin
SJ
Department of Cellular & Physiological Sciences and the Diabetes Research Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.
Doudet
Doris J
DJ
Studenov
Andrei R
AR
Nian
Cuilan
C
Ruth
Thomas J
TJ
Gambhir
Sanjiv Sam
SS
McIntosh
Christopher H S
CH
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging; D005240:Feasibility Studies; D005260:Female; D017930:Genes, Reporter; D006085:Graft Survival; D006147:Guanine / Q000031:analogs & derivatives; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D049268:Positron-Emission Tomography / Q000379:methods*; D014185:Transplantation, Isogeneic
C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D006147:Guanine