Positron-Emission Tomography Imaging of Early Events after Transplantation of Islets of Langerhans

Toso, Christian; Zaidi, Habib; Morel, Philippe; Armanet, Mathieu; Andrès, Axel; Pernin, Nadine; Baertschiger, Reto M.; Slosman, Daniel O.; Bühler, Léo H.; Bosco, Domenico; Berney, Thierry

doi:10.1097/01.tp.0000149501.50870.9d

Cited by 78 publications

(55 citation statements)

References 11 publications

(11 reference statements)

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“…In a syngeneic rat model of IPIT, an average of 43% of the infused tracer radioactivity was found in the liver 1 h after islet transplantation (Toso et al, 2005). Based on these and other observations, the authors suggested that inflammatory events immediately following IPIT (i.e.…”

Section: Discussionmentioning

confidence: 95%

Effect of nicotinamide on early graft failure following intraportal islet transplantation

et al. 2009

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Intraportal islet transplantation (IPIT) may potentially cure Type 1 diabetes mellitus; however, graft failure in the early post-transplantation period presents a major obstacle. In this study, we tested the ability of nicotinamide to prevent early islet destruction in a syngeneic mouse model. Mice (C57BL/6) with chemically-induced diabetes received intraportal transplants of syngeneic islet tissue in various doses. Islets were cultured for 24 h in medium with or without 10 mM nicotinamide supplementation. Following IPIT, islet function was confirmed by an intraperitoneal glucose tolerance test (IPGTT) and hepatectomy. The effects of nicotinamide were evaluated by blood glucose concentration, serum monocyte chemoattractant protein-1 (MCP-1) concentration, and immunohistology at 3 h and 24 h after IPIT. Among the various islet doses, an infusion of 300 syngeneic islets treated with nicotinamide exhibited the greatest differences in glucose tolerance between recipients of treated and untreated (i.e., control) islets. One day after 300 islet equivalent (IEQ) transplantation, islets treated with nicotinamide were better granulated than the untreated islets (P = 0.01), and the recipients displayed a slight decrease in serum MCP-1 concentration, as compared to controls. After 15 days, recipients of nicotinamide-pretreated islets showed higher levels of graft function (as measured by IPGTT) than controls. The pretreatment also prolonged graft survival (＞ 100 days) and function; these were confirmed by partial hepatectomy, which led to the recurrence of diabetes. Pretreatment of islet grafts with nicotinamide may prevent their deterioration on the early period following IPIT in a syngeneic mouse model.

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Section: Discussionmentioning

confidence: 95%

Effect of nicotinamide on early graft failure following intraportal islet transplantation

et al. 2009

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“…Similarly, taking advantage of bicarbonate and/or organic anion transporters expressed by pancreatic acinar cells, [ 11 C]acetate has been used to visualize the exocrine pancreas [6,7]. In addition, animal studies show that 2-[ 18 F]fluoro-2-deoxy-D-glucose may be useful in imaging recently transplanted islets [8]. Markmann et al [9] recently reported that transplanted cadaveric islets, 14 months posttransplantation, induce peri-islet cell mass fat deposits that are visible by chemical shift gradient-echo magnetic resonance imaging (MRI).…”

Section: Introductionmentioning

confidence: 99%

Visualizing pancreatic β-cell mass with [11C]DTBZ

Simpson

Souza

Witkowski

et al. 2006

Nuclear Medicine and Biology

109

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Abstractβ-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, β-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by β cells, with [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocininduced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in β cells with the use of [ 11 C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.

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“…However, with repeated transplantations or larger graft volumes, a temporary rise in portal venous pressure (11), accompanied by a reduction in portal blood flow and increase in liver enzymes (12), has been found. (13)(14)(15) [ 18 (16,17).…”

Section: Islet Transplantation Is a Treatment Option For Selected Patmentioning

confidence: 99%

Positron Emission Tomography in Clinical Islet Transplantation

Eriksson

Eich²,

Sundín

et al. 2009

American Journal of Transplantation

146

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The fate of islets in clinical transplantation is unclear. To elude on this positron emission tomography combined with computed tomography (PET/CT) was performed for 60 min during islet transplantation in five patients receiving six transplants.A fraction of the islets (23%) were labeled with 18F-fluorodeoxyglucose ([ 18 F]FDG) and carefully mixed with unlabeled islets just prior to intraportal transplantation. The peak radioactivity concentration in the liver was found at 19 min after start of islet infusion and corresponded to only 75% of what was expected, indicating that islets are lost during the transplantation procedure. No accumulation of radioactivity was found in the lungs. A nonphysiological peak of C-peptide was found in plasma during and immediately after transplantation in all subjects. Distribution in the liver was heterogeneous with wide variations in location and concentration. Islets found in areas with concentrations of >400 IEQ/cc liver tissue varied between 1% and 32% of the graft in different subjects. No side effects attributed to the PET/CT procedure were found. Clinical outcome in all patients was comparable to that previously observed indicating that the [ 18 F]FDG labeling procedure did not harm the islets. The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation.

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Positron-Emission Tomography Imaging of Early Events after Transplantation of Islets of Langerhans

Cited by 78 publications

References 11 publications

Effect of nicotinamide on early graft failure following intraportal islet transplantation

Effect of nicotinamide on early graft failure following intraportal islet transplantation

Visualizing pancreatic β-cell mass with [11C]DTBZ

Positron Emission Tomography in Clinical Islet Transplantation

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