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

被引:0
作者
Puuvuori, Emmi [1 ]
Rokka, Johanna [2 ]
Carlsson, Per-Ola [3 ]
Li, Zhanchun [3 ]
Eriksson, Jonas [1 ]
Eriksson, Olof [1 ]
机构
[1] Uppsala Univ, Dept Med Chem, Sci Life Lab, Dag Hammarskjoldsv 14C,3rd Floor, S-75183 Uppsala, Sweden
[2] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden
[3] Uppsala Univ, Dept Med Cell Biol, Uppsala, Sweden
基金
瑞典研究理事会;
关键词
SV2C;
D O I
10.1038/s41598-021-04188-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. [C-11]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 [C-11]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 [C-11]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 [C-11]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 [C-11]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 [C-11]UCB-J does not appear to have sufficient sensitivity for this application.
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页数:9
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