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There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the \u03b3-aminobutyric acid A receptors (GABA<jats:sub>A<\/jats:sub>Rs) in pancreatic islets and the fact that GABA<jats:sub>A<\/jats:sub>R agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [<jats:sup>11<\/jats:sup>C]flumazenil ([<jats:sup>11<\/jats:sup>C]FMZ) could serve as a marker of the endocrine mass of the pancreas. The in vivo uptake of [<jats:sup>11<\/jats:sup>C]FMZ in pig pancreas was evaluated by PET\/CT, either tracer alone or after blockade of GABA<jats:sub>A<\/jats:sub>R by unlabeled flumazenil. The pancreatic binding of [<jats:sup>11<\/jats:sup>C]FMZ was investigated in vitro with frozen sections of pig pancreas as well as human organ donors, in addition to isolated mouse and human islets and exocrine preparations. The expression of GABA<jats:sub>A<\/jats:sub>R subunits in pig, human and mouse pancreas was explored by immunohistochemistry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Strong specific in vivo uptake of [<jats:sup>11<\/jats:sup>C]FMZ was observed in the pig brain as expected, but in the pancreas the signal was moderate and only partially reduced by blockade. In vitro experiments revealed a positive but weak and variable binding of [<jats:sup>11<\/jats:sup>C]FMZ in islets compared to exocrine tissue in the mouse, pig and human pancreas. In pig and mouse pancreatic islets we identified the GABA<jats:sub>A<\/jats:sub>R subunits \u03b22 and \u03b32 but not \u03b12. In the human pancreas from non-diabetic donors, we have identified the \u03b12, \u03b22 (although weak) and \u03b32 subunits, whereas from a T2D donor the \u03b12 subunit was missing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that [<jats:sup>11<\/jats:sup>C]FMZ bind to GABA<jats:sub>A<\/jats:sub>Rs in the islets, but not with a sufficient contrast or magnitude to be implemented as an in vivo PET marker for the endocrine mass of the pancreas. However, GABA<jats:sub>A<\/jats:sub>Rs with different subunits are widely expressed in the endocrine cells within the pancreas in pig, human and mouse. Hence, the GABA<jats:sub>A<\/jats:sub>R could still be a potential imaging target for the endocrine cells of the pancreas but would require tracers with higher affinity and selectivity for individual GABA<jats:sub>A<\/jats:sub>R subunits.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13550-024-01176-5","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T18:33:11Z","timestamp":1733164391000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PET imaging of GABAA receptors in pancreatic islets by [11C]flumazenil"],"prefix":"10.1186","volume":"14","author":[{"given":"Fa\u00efza","family":"Maloum-Rami","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Antoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2515-8790","authenticated-orcid":false,"given":"Olof","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Espes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"1176_CR1","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1016\/j.molimm.2005.07.025","volume":"43","author":"S Alam","year":"2006","unstructured":"Alam S, Laughton DL, Walding A, Wolstenholme AJ. 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The studies were planned and performed in according to the 3Rs principle and to the ARRIVE guidelines for animal research and were approved by the animal Research Ethical Committee of the Uppsala Region (Ethical approval # 5.8.18-15648\/2019 for experiments with pig and <i>dnr<\/i> 5.8.18-03604 for experiments with mice). The use of human tissues from Uppsala Biobank (registration #827) was approved by the Regional Ethics Board of Uppsala, Sweden (now the Swedish Ethical Review Authority) (2011\/473, Ups 02-577, 2015\/401) and were collected and treated according to local institutional and Swedish national rules and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"DE is co-founder and shareholder of OneTwo Analytics AB. OE is co-founder, employee and minority shareholder of Antaros Tracer AB. The remaining authors declare that they have no competing interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"122"}}