Positron Emission Tomography Ligand [11C]5-Hydroxy-Tryptophan Can Be Used as a Surrogate Marker for the Human Endocrine Pancreas

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 β-cells, with healthy volunteers (HVs). C-peptide–negative (i.e., insulin-deficient) T1D subjects (n = 10) and HVs (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 HVs, with large interindividual 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 β-cells normally are the major constituent of the islets. [11C]5-HTP retention in the pancreas was reduced in T1D compared with nondiabetic subjects. Accumulation of [11C]5-HTP in the pancreas of both HVs and subjects with T1D was in agreement with previously reported morphological observations on the β-cell volume, implying that [11C]5-HTP retention is a useful noninvasive surrogate marker for the human endocrine pancreas.

Pancreatic perfusion and subsequent response to glucose in healthy individuals and patients with type 1 diabetes

“…In previous investigations, pancreatic perfusion in individuals with type 1 diabetes has been shown either not to change or to have a tendency to decrease [2,7]. Experience from animal studies [4][5][6] is suggestive that the perfusion difference between insulin-deficient and healthy animals mainly reflects the islet vascular component.…”

“…Positron emission tomography (PET) with radioactive labelled water ([ 15 O]H 2 O) as a tracer is a well-established tool to study changes in perfusion in human organs and has previously been used to study pancreatic perfusion under basal conditions [1,2]. Pancreatic perfusion is normally closely related to tissue function, for example secretin, a hormone which stimulates exocrine secretion, also increases pancreatic perfusion in humans [3].…”

In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use

“…Integrated pancreatic uptake is likely to be more informative, as it reflects total beta cell mass in the pancreas for an ideal tracer. This may require an independent measure of pancreas volume in cases of low pancreatic uptake when delineation of the pancreas by radiotracer uptake alone is challenging [6,7], or when interfering signal is present from high concentrations of excreted tracer metabolites in neighbouring tissues such as renal cortex or intestine.…”

Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus

“…A positron emission tomography (PET) with radioactive labeled water ([ 15 O]H 2 O) and [ 11 C]‐5‐hydroxytryptophan ([ 11 C]‐5‐HTP) was performed as described previously11 in 2 of the patients before explantation of the devices to evaluate the in vivo kinetics over the immune barrier of the device.…”