Potential of [11C]UCB-J as a PET tracer for islets of Langerhans

Emmi Puuvuori,Olof Eriksson,Zhanchun Li,Johanna Rokka,Jonas Eriksson,Per-Ola Carlsson

doi:10.1038/s41598-021-04188-6

Emmi Puuvuori, Olof Eriksson + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-04188-6

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Abstract

Biomarkers for the measurement of islets of Langerhans could help elucidate the etiology of diabetes. Synaptic vesicle glycoprotein 2 A (SV2A) is a potential marker reported to be localized in the endocrine pancreas. [11C]UCB-J is a novel positron emission tomography (PET) radiotracer that binds to SV2A and was previously evaluated as a synaptic marker in the central nervous system. Here, we evaluated whether [11C]UCB-J could be utilized as a PET tracer for the islets of Langerhans in the pancreas by targeting SV2A. The mRNA transcription of SV2A was evaluated in human isolated islets of Langerhans and exocrine tissue. In vitro autoradiography was performed on pancreas and brain sections from rats and pigs, and consecutive sections were immunostained for insulin. Sprague–Dawley rats were examined with PET-MRI and ex vivo autoradiography at baseline and with administration of levetiracetam (LEV). Similarly, pigs were examined with dynamic PET-CT over the pancreas and brain after administration of [11C]UCB-J at baseline and after pretreatment with LEV. In vivo radioligand binding was assessed using a one-compartment tissue model. The mRNA expression of SV2A was nearly 7 times higher in endocrine tissue than in exocrine tissue (p < 0.01). In vitro autoradiography displayed focal binding of [11C]UCB-J in the pancreas of rats and pigs, but the binding pattern did not overlap with the insulin-positive areas or with ex vivo autoradiography. In rats, pancreas binding was higher than that in negative control tissues but could not be blocked by LEV. In pigs, the pancreas and brain exhibited accumulation of [11C]UCB-J above the negative control tissue spleen. While brain binding could be blocked by pretreatment with LEV, a similar effect was not observed in the pancreas. Transcription data indicate SV2A to be a valid target for imaging islets of Langerhans, but [11C]UCB-J does not appear to have sufficient sensitivity for this application.

Highlights

The current understanding of beta cell mass (BCM) within the Islets of Langerhans of the pancreas in each individual during the progression of human diabetes is still unclear
Isoform SV2B and SV2C transcription did not differ between islets and exocrine tissue and was generally low, especially for SV2C
Binding in the pancreas from rats (Fig. 2c) and pigs (Fig. 2d) exhibited a low exocrine background and focal binding pattern, suggestive of binding to Langerhans islets. In line with this reasoning, binding in INS-1 sections (Fig. 2b) was generally higher than the exocrine background but in a similar range as the focal uptake seen in rat pancreas

Summary

Introduction

The current understanding of beta cell mass (BCM) within the Islets of Langerhans of the pancreas in each individual during the progression of human diabetes is still unclear. One possibility is to harness already established PET tracers that are selective for the endocrine pancreas. This would rapidly enable imaging and quantification of the islet mass, which could serve as a substitute for BCM. Our group successfully imaged islet masses with [11C]5-hydroxytryptophan, a precursor of serotonin present in all endocrine cells in the pancreas, but the demanding radiochemistry process makes widespread use of the tracer c hallenging[2,3,4]. A possible drawback of nanobodies is the unclear nature of their immunogenicity due to their camelid derivate origin, which might hinder the process of the clinical use of the t racer[6]

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