The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas

  1. Olle Korsgren7
  1. 1Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, SE-751 83, Uppsala, Sweden
  2. 2Department of Medical Cell Biology, Uppsala University, SE-751 83, Uppsala, Sweden
  3. 3Department of Radiology, Oncology and Radiation Sciences, Uppsala University, SE-751 83, Uppsala, Sweden
  4. 4Department of Surgical Sciences, Uppsala University, SE-751 83, Uppsala, Sweden
  5. 5AstraZeneca R&D, Mölndal, 431 50, Sweden
  6. 6Department of Medical Sciences, Uppsala University, SE-751 85, Uppsala, Sweden
  7. 7Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 83, Uppsala, Sweden
  1. *Corresponding Author: Olof Eriksson, E-mail: olof.eriksson{at}pet.medchem.uu.se

Abstract

In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).

C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [11C]5-Hydroxy-Tryptophan ([11C]5-HTP).

A significant accumulation of [11C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [11C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.

[11C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [11C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [11C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.

  • Received December 13, 2013.
  • Accepted May 14, 2014.

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  1. Diabetes
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