Positron Emission Tomography to Assess the Outcome of Intraportal Islet Transplantation.
No imaging methodology currently exists to monitor viable islet mass after clinical intraportal islet transplantation. We investigated the potential of the endocrine positron emission tomography (PET) marker [(11)C]5-hydroxytryptophan ([(11)C]5-HTP) for this purpose. In a preclinical proof-of-concept study, the ex vivo and in vivo [(11)C]5-HTP signal was compared with the number of islets transplanted in rats. In a clinical study, human subjects with an intraportal islet graft (n = 8) underwent two [(11)C]5-HTP PET and MRI examinations 8 months apart. The tracer concentration in the liver as a whole, or in defined hotspots, was correlated to measurements of islet graft function. In rat, hepatic uptake of [(11)C]5-HTP correlated with the number of transplanted islets. In human subjects, uptake in hepatic hotspots showed a correlation with metabolic assessments of islet function. Change in hotspot standardized uptake value (SUV) predicted loss of graft function in one subject, whereas hotspot SUV was unchanged in subjects with stable graft function. The endocrine marker [(11)C]5-HTP thus shows a correlation between hepatic uptake and transplanted islet function and promise as a tool for noninvasive detection of viable islets. The evaluation procedure described can be used as a benchmark for novel agents targeting intraportally transplanted islets.
Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Uppsala, Sweden olof.eriksson@pet.medchem.uu.se.
Olof
O
Eriksson
Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Uppsala, Sweden.
Ramkumar
R
Selvaraju
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Torsten
T
Eich
Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Uppsala, Sweden.
Mariam
M
Willny
Division of Medical Imaging and Technology, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Torkel B
TB
Brismar
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Lina
L
Carlbom
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Håkan
H
Ahlström
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Gunnar
G
Tufvesson
Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Torbjörn
T
Lundgren
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Olle
O
Korsgren
D006916:5-Hydroxytryptophan / Q000032:analysis; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging; D064368:Healthy Volunteers; D006801:Humans; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D051381:Rats; D012189:Retrospective Studies
D006916:5-Hydroxytryptophan