Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals With Type 1 Diabetes

Theodorus J. P. Jansen; Mijke Buitinga; Marti Boss; Michiel F. Nijhoff; Maarten Brom; Bastiaan E. de Galan; Marinette van der Graaf; Sebastiaan van Koeverden; Marie-Christine Vantyghem; Amandine Beron; Francois Pattou; Marten A. Engelse; Irina Velikyan; Olof Eriksson; Eelco J. P. de Koning; Martin Gotthardt

doi:10.2337/db22-0884

Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals With Type 1 Diabetes

Theodorus J. P. Jansen, Mijke Buitinga, Marti Boss^*, Michiel F. Nijhoff, Maarten Brom, Bastiaan E. de Galan, Marinette van der Graaf, Sebastiaan van Koeverden, Marie-Christine Vantyghem, Amandine Beron, Francois Pattou, Marten A. Engelse, Irina Velikyan, Olof Eriksson, Eelco J. P. de Koning, Martin Gotthardt

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to noninvasively monitor the fate and survival of transplanted islets over time are of great potential value. We used [Ga-68]Ga-NODAGA-exendin-4 (Ga-68-exendin) positron emission tomography (PET)/computed tomography (CT) imaging to demonstrate the feasibility of quantifying b-cellmass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, nine after ITx with functional islet grafts and four control patients not treated with ITx. beta-Cell function was measured by mixed-meal tolerance test. With dynamic Ga-68-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using MRI and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of Ga-68-exendin in the ITx group compared with the control group (median 0.55 [interquartile range 0.51-0.63] vs. 0.43 [0.42-0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in a majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx.

Original language	English
Pages (from-to)	898-907
Number of pages	10
Journal	Diabetes
Volume	72
Issue number	7
DOIs	https://doi.org/10.2337/db22-0884
Publication status	Published - 1 Jul 2023

Keywords

POSITRON-EMISSION-TOMOGRAPHY
HEPATIC STEATOSIS
RECEPTOR
XENOTRANSPLANTATION
HYPERGLYCEMIA
PREVALENCE
EXPRESSION
PANCREAS
MELLITUS
GRAFTS

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Cite this

Jansen, T. J. P., Buitinga, M., Boss, M., Nijhoff, M. F., Brom, M., de Galan, B. E., van der Graaf, M., van Koeverden, S., Vantyghem, M.-C., Beron, A., Pattou, F., Engelse, M. A., Velikyan, I., Eriksson, O., de Koning, E. J. P., & Gotthardt, M. (2023). Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals With Type 1 Diabetes. Diabetes, 72(7), 898-907. https://doi.org/10.2337/db22-0884

@article{57a2365ad9d64e71b1736212cda60228,

title = "Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals With Type 1 Diabetes",

abstract = "Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to noninvasively monitor the fate and survival of transplanted islets over time are of great potential value. We used [Ga-68]Ga-NODAGA-exendin-4 (Ga-68-exendin) positron emission tomography (PET)/computed tomography (CT) imaging to demonstrate the feasibility of quantifying b-cellmass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, nine after ITx with functional islet grafts and four control patients not treated with ITx. beta-Cell function was measured by mixed-meal tolerance test. With dynamic Ga-68-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using MRI and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of Ga-68-exendin in the ITx group compared with the control group (median 0.55 [interquartile range 0.51-0.63] vs. 0.43 [0.42-0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in a majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx.",

keywords = "POSITRON-EMISSION-TOMOGRAPHY, HEPATIC STEATOSIS, RECEPTOR, XENOTRANSPLANTATION, HYPERGLYCEMIA, PREVALENCE, EXPRESSION, PANCREAS, MELLITUS, GRAFTS",

author = "Jansen, {Theodorus J. P.} and Mijke Buitinga and Marti Boss and Nijhoff, {Michiel F.} and Maarten Brom and {de Galan}, {Bastiaan E.} and {van der Graaf}, Marinette and {van Koeverden}, Sebastiaan and Marie-Christine Vantyghem and Amandine Beron and Francois Pattou and Engelse, {Marten A.} and Irina Velikyan and Olof Eriksson and {de Koning}, {Eelco J. P.} and Martin Gotthardt",

year = "2023",

month = jul,

day = "1",

doi = "10.2337/db22-0884",

language = "English",

volume = "72",

pages = "898--907",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "7",

}

Jansen, TJP, Buitinga, M, Boss, M, Nijhoff, MF, Brom, M, de Galan, BE, van der Graaf, M, van Koeverden, S, Vantyghem, M-C, Beron, A, Pattou, F, Engelse, MA, Velikyan, I, Eriksson, O, de Koning, EJP & Gotthardt, M 2023, 'Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging: A Proof-of-Concept Study in Individuals With Type 1 Diabetes', Diabetes, vol. 72, no. 7, pp. 898-907. https://doi.org/10.2337/db22-0884

TY - JOUR

T1 - Monitoring β-Cell Survival After Intrahepatic Islet Transplantation Using Dynamic Exendin PET Imaging

T2 - A Proof-of-Concept Study in Individuals With Type 1 Diabetes

AU - Jansen, Theodorus J. P.

AU - Buitinga, Mijke

AU - Boss, Marti

AU - Nijhoff, Michiel F.

AU - Brom, Maarten

AU - de Galan, Bastiaan E.

AU - van der Graaf, Marinette

AU - van Koeverden, Sebastiaan

AU - Vantyghem, Marie-Christine

AU - Beron, Amandine

AU - Pattou, Francois

AU - Engelse, Marten A.

AU - Velikyan, Irina

AU - Eriksson, Olof

AU - de Koning, Eelco J. P.

AU - Gotthardt, Martin

PY - 2023/7/1

Y1 - 2023/7/1

N2 - Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to noninvasively monitor the fate and survival of transplanted islets over time are of great potential value. We used [Ga-68]Ga-NODAGA-exendin-4 (Ga-68-exendin) positron emission tomography (PET)/computed tomography (CT) imaging to demonstrate the feasibility of quantifying b-cellmass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, nine after ITx with functional islet grafts and four control patients not treated with ITx. beta-Cell function was measured by mixed-meal tolerance test. With dynamic Ga-68-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using MRI and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of Ga-68-exendin in the ITx group compared with the control group (median 0.55 [interquartile range 0.51-0.63] vs. 0.43 [0.42-0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in a majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx.

AB - Intrahepatic transplantation of islets of Langerhans (ITx) is a treatment option for individuals with complicated type 1 diabetes and profoundly unstable glycemic control, but its therapeutic success is hampered by deterioration of graft function over time. To improve ITx strategies, technologies to noninvasively monitor the fate and survival of transplanted islets over time are of great potential value. We used [Ga-68]Ga-NODAGA-exendin-4 (Ga-68-exendin) positron emission tomography (PET)/computed tomography (CT) imaging to demonstrate the feasibility of quantifying b-cellmass in intrahepatic islet grafts in 13 individuals with type 1 diabetes, nine after ITx with functional islet grafts and four control patients not treated with ITx. beta-Cell function was measured by mixed-meal tolerance test. With dynamic Ga-68-exendin PET/CT images, we determined tracer accumulation in hepatic hotspots, and intrahepatic fat was assessed using MRI and spectroscopy. Quantification of hepatic hotspots showed a significantly higher uptake of Ga-68-exendin in the ITx group compared with the control group (median 0.55 [interquartile range 0.51-0.63] vs. 0.43 [0.42-0.45]). GLP-1 receptor expression was found in transplanted islets by immunohistochemistry. Intrahepatic fat was not detected in a majority of the individuals. Our study provides the first clinical evidence that radiolabeled exendin imaging can be used to monitor viable transplanted islets after intraportal ITx.

KW - POSITRON-EMISSION-TOMOGRAPHY

KW - HEPATIC STEATOSIS

KW - RECEPTOR

KW - XENOTRANSPLANTATION

KW - HYPERGLYCEMIA

KW - PREVALENCE

KW - EXPRESSION

KW - PANCREAS

KW - MELLITUS

KW - GRAFTS

U2 - 10.2337/db22-0884

DO - 10.2337/db22-0884

M3 - Article

C2 - 37068261

SN - 0012-1797

VL - 72

SP - 898

EP - 907

JO - Diabetes

JF - Diabetes

IS - 7

ER -