TY - JOUR
T1 - Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas
AU - Jansen, Theodorus J. P.
AU - Tokgoz, Sevilay
AU - Buitinga, Mijke
AU - van Lith, Sanne A. M.
AU - Joosten, Lieke
AU - Frielink, Cathelijne
AU - Smeets, Esther M. M.
AU - Stommel, Martijn W. J.
AU - van der Kolk, Marion B.
AU - de Galan, Bastiaan E.
AU - Brom, Maarten
AU - Boss, Marti
AU - Gotthardt, Martin
PY - 2024/10/15
Y1 - 2024/10/15
N2 - Background Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with In-111-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of In-111-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo Results Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants. Conclusion Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass. Trial registration ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496. ClinicalTrials.gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508.
AB - Background Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans. Fourteen adults with pancreas tumours were injected with In-111-labeled exendin-4 prior to pancreatic resection. In resected pancreas tissue, endocrine-exocrine ratios of tracer uptake were determined by digital autoradiography and accumulation of In-111-labeled exendin-4 was compared to insulin and GLP-1 receptor staining. Of four participants, abdominal single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired to quantify pancreatic uptake in vivo Results Tracer uptake was predominantly present in the endocrine pancreas (endocrine-exocrine ratio: 3.6 [2.8-10.8]. Tracer accumulation showed overlap with insulin-positive regions, which overlapped with GLP-1 receptor positive areas. SPECT imaging showed pancreatic uptake of radiolabelled exendin in three participants. Conclusion Radiolabelled exendin specifically accumulates in the islets of Langerhans in human pancreas tissue. The clear overlap between regions positive for insulin and the GLP-1 receptor substantiate the beta cell specificity of the tracer. Radiolabelled exendin is therefore a valuable imaging agent for human beta cell mass quantification and has the potential to be used for a range of applications, including improvement of diabetes treatment by assessment of the effects of current and novel diabetes therapies on the beta cell mass. Trial registration ClinicalTrials.gov NCT03889496, registered 26,032,019, URL https://clinicaltrials.gov/study/NCT03889496?term=NCT03889496. ClinicalTrials.gov NCT04733508, registered 02022021, URL https://clinicaltrials.gov/study/NCT04733508.
KW - Beta cell mass
KW - Endocrine-to-exocrine ratio
KW - Human pancreas
KW - Radiolabelled exendin
KW - SPECT/CT imaging
KW - MONOAMINE TRANSPORTER-2 VMAT2
KW - MASS
KW - EXPRESSION
KW - MOUSE
U2 - 10.1186/s13550-024-01159-6
DO - 10.1186/s13550-024-01159-6
M3 - Article
SN - 2191-219X
VL - 14
JO - EJNMMI Research
JF - EJNMMI Research
IS - 1
M1 - 96
ER -