Enhanced Cholinergic Response in Pancreata of Nonhuman Primates with Impaired Glucose Tolerance Shown on [¹⁸F]Fluorobenzyltrozamicol Positron Emission Tomography

Abstract

Background: Islet cell adaptation to insulin resistance in type 2 diabetes mellitus may be due in part to increased stimulation of beta cells by the autonomic nervous system. The parasympathetic neurotransmitter acetylcholine (ACh) mediates insulin release via M3 muscarinic receptors on islet beta cells. The vesicular ACh transporter (VAChT) receptor correlates with cholinergic activity in vivo. The positron emission tomography (PET) radiotracer (+)-4-[18 F]fluorobenzyltrozamicol ([ 18 F]FBT) binds to the VAChT receptor on presynaptic cholinergic neurons and can be quantified by PET. In this study, we utilize [18 F]FBT PET to demonstrate pancreatic cholinergic activity before and after dextrose infusion in nonhuman primates with normal (NGT) and impaired (IGT) glucose tolerance. Methods: Seven adult female vervet (Chlorocebus aethiops) monkeys were maintained on an atherogenic Western diet. They were divided into two groups: four with NGT and three with IGT. Each subject underwent [

Molecular imaging of β-cells: diabetes and beyond

“…In 2004, Clark et al first reported that the pancreas was intensely 18 F-FBT avid and was clearly visualized in the 18 F-FBT PET images of mice, rhesus monkeys, and adult human volunteers [152]. 18 F-FBT was further used as a tool to investigate glucose tolerance in adult female monkeys [153]. Considering the reduced cholinergic innervation in T1DM and the role of the parasympathetic neurotransmitter ACh in insulin production, Clark and co-authors further tested the feasibility of dual radiotracer analysis in identifying neurofunctional changes in T1DM using 18 F-FBT and 4-3 H-DAMP, with the former probe targeting VAChT and the latter probe binding to M3 muscarinic receptors on β-cells [154].…”

Development of 99mTc-Labeled Pyridyl Benzofuran Derivatives To Detect Pancreatic Amylin in Islet Amyloid Model Mice

“…T2DM is characterized by a progressive decline of the pancreatic β-cell mass (BCM), which is responsible for insulin secretion failure and hyperglycemia . In T2DM patients, the BCM can be 40–60% smaller than in healthy controls. − Many radioactive imaging probes targeting pancreatic β-cells have been developed to assess the BCM, such as 11 C-DTBZ , and 18 F-labeled DTBZ analogues, − 18 F-FBT, , and 111 In-exendin . β-Cell imaging can give us critical information on the progression of T2DM.…”

“…1 In T2DM patients, the BCM can be 40−60% smaller than in healthy controls. 4−6 Many radioactive imaging probes targeting pancreatic β-cells have been developed to assess the BCM, such as 11 C-DTBZ 7,8 and 18 F-labeled DTBZ analogues, 9−11 18 F-FBT, 12,13 and 111 Inexendin. 14 β-Cell imaging can give us critical information on the progression of T2DM.…”