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Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following intravenous administration.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Procedures<\/jats:title>\n            <jats:p>Twelve male Wistar rats were divided into four groups and subjected to intravenous or oral [<jats:sup>18<\/jats:sup>F]MC225 administration protocols: G<jats:sub>1<\/jats:sub> (intravenous route), G<jats:sub>2<\/jats:sub> (oral administration without fasting), G<jats:sub>3<\/jats:sub> (oral administration with fasting), and G<jats:sub>4<\/jats:sub> (oral administration with fasting following administration of the P-gp inhibitor tariquidar). Dynamic brain imaging, late abdominal imaging, <jats:italic>ex vivo<\/jats:italic> biodistribution, and metabolite analysis were conducted to assess tracer distribution.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In the brain, oral administration yielded lower values compared with intravenous administration, resulting in a reduction in the tissue-to-plasma ratio by approximately 51% for the cortex and 45% for the midbrain and cerebellum. Fasting improved radioactivity uptake, aiding brain visualization. Unexpectedly, administration of the P-gp inhibitor tariquidar did not increase brain concentration, suggesting a signal that was dominated by non-specific uptake, possibly due to instability of [<jats:sup>18<\/jats:sup>F]MC225 in the GI tract. Metabolite analysis in G<jats:sub>4<\/jats:sub> indicated a significant presence of polar metabolites.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Oral administration of [<jats:sup>18<\/jats:sup>F]MC225 faces challenges and, at this stage, cannot be used to quantify P-gp function. Further research to assess tracer stability and metabolism in the stomach and intestine will be essential for advancing the feasibility of oral tracer administration.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11307-024-01975-1","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T16:41:48Z","timestamp":1736872908000},"page":"89-98","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oral Administration of [18F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study"],"prefix":"10.1007","volume":"27","author":[{"given":"Giordana","family":"Salvi de Souza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiane R. G.","family":"Furini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen W. 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