Correspondence
Visualization of Early Engraftment in Clinical Islet Transplantation by Positron-Emission Tomography
N Engl J Med 2007; 356:2754-2755June 28, 2007
- Article
To the Editor:
Although islet transplantation is an option for patients with type 1 diabetes, even those who become insulin-independent after engraftment have islet-graft function that is estimated to be less than 30% of that in a healthy person.1 In fact, most patients resume insulin treatment within 2 years after transplantation.2
Islet-cell transplantation is accomplished by embolizing the islets by means of the portal vein into the liver.3 Because available tools to study transplanted islets have been limited, the liver has been considered a “black box” in clinical islet transplantation. Here we demonstrate the use of scanning with positron-emission tomography (PET) combined with computed tomography (CT) to visualize the peritransplantation phase of islet transplantation in a single subject. The recipient is a 46-year-old man with a 39-year history of type 1 diabetes. Islets (430,000 islet equivalents) were isolated from the pancreas of a multiorgan donor, and 100,000 islet equivalents were allowed to internalize 18F-fluorodeoxyglucose (18F-FDG) (the half-life of fluorine-18 is 110 minutes) immediately before transplantation. In vitro autoradiography indicated that 96.7% of the radioactivity was confined to the islets. Labeled and unlabeled islets, carefully mixed, were infused into the portal vein. Labeled islets were readily visualized, demonstrating a heterogeneous distribution in the liver. They were concentrated in multifocal “hot spots” in the right lobe (Figure 1AFigure 1
PET–CT Images of Labeled Islets, Radioactivity Uptake, and Plasma C-Peptide Levels during and after Transplantation.), with no evident shunting to the lungs. Only 53% of the administered radioactivity was detected in the liver, suggesting that half the transplanted islet cells were damaged to the extent that the 18F-FDG they contained was released during the first few minutes after transplantation (Figure 1B). The residual radioactivity was evenly distributed throughout the body. A parallel, marked increase in plasma C peptide (Figure 1C) was observed, also indicating islet destruction.4 After 2 weeks, the patient's plasma C-peptide level after an overnight fast was 1.18 ng per milliliter (concomitant plasma glucose level, 85 mg per deciliter), and his meal-stimulated plasma C-peptide level was 1.63 ng per milliliter (plasma glucose level, 156 mg per deciliter), even with insulin treatment to optimize islet engraftment. The satisfactory outcome of the transplantation, despite the marked loss of islets immediately after transplantation, indicates that the islets were of good quality and suggests that the substantial loss of islets described here is a common phenomenon in clinical islet transplantation.4,5 Since the submission of this letter, another patient has undergone transplantation with the same procedure and with similar results as in this case.
The main advantages of the PET–CT technology as shown here are that it is readily available in most centers performing islet transplantation and that it allows real-time measurement of islet survival and distribution after transplantation. Thus, this technology seems to be promising as a means for assessing various strategies to improve early islet engraftment after intraportal transplantation and for evaluating alternative sites of implantation.
Torsten Eich, M.D.
Olof Eriksson, M.Sc.
Uppsala University, S-751 85 Uppsala, SwedenTorbjörn Lundgren, M.D.
Karolinska Institutet, S-141 86 Stockholm, Sweden
torbjorn.lundgren@karolinska. se for the Nordic Network for Clinical Islet Transplantation
Supported by grants from the Swedish Medical Research Council, the Nordic Insulin Fund, the Ernfors Family Fund, Barn Diabetes Fonden, the Swedish Diabetes Association, the Juvenile Diabetes Foundation International, and the National Institutes of Health.
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