Potential of [11C]UCB-J as a PET tracer for islets of Langerhans
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-04188-6 |
| _version_ | 1819173974085468160 |
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| author | Emmi Puuvuori Johanna Rokka Per-Ola Carlsson Zhanchun Li Jonas Eriksson Olof Eriksson |
| author_facet | Emmi Puuvuori Johanna Rokka Per-Ola Carlsson Zhanchun Li Jonas Eriksson Olof Eriksson |
| author_sort | Emmi Puuvuori |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T20:31:36Z |
| format | Article |
| id | doaj.art-b3eca6b9d3604d2e89ce5f7e54920b6c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T20:31:36Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b3eca6b9d3604d2e89ce5f7e54920b6c2022-12-21T18:13:36ZengNature PortfolioScientific Reports2045-23222021-12-011111910.1038/s41598-021-04188-6Potential of [11C]UCB-J as a PET tracer for islets of LangerhansEmmi Puuvuori0Johanna Rokka1Per-Ola Carlsson2Zhanchun Li3Jonas Eriksson4Olof Eriksson5Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityDepartment of Public Health and Caring Sciences, Uppsala UniversityDepartment of Medical Cell Biology, Uppsala UniversityDepartment of Medical Cell Biology, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityAbstract 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.https://doi.org/10.1038/s41598-021-04188-6 |
| spellingShingle | Emmi Puuvuori Johanna Rokka Per-Ola Carlsson Zhanchun Li Jonas Eriksson Olof Eriksson Potential of [11C]UCB-J as a PET tracer for islets of Langerhans Scientific Reports |
| title | Potential of [11C]UCB-J as a PET tracer for islets of Langerhans |
| title_full | Potential of [11C]UCB-J as a PET tracer for islets of Langerhans |
| title_fullStr | Potential of [11C]UCB-J as a PET tracer for islets of Langerhans |
| title_full_unstemmed | Potential of [11C]UCB-J as a PET tracer for islets of Langerhans |
| title_short | Potential of [11C]UCB-J as a PET tracer for islets of Langerhans |
| title_sort | potential of 11c ucb j as a pet tracer for islets of langerhans |
| url | https://doi.org/10.1038/s41598-021-04188-6 |
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