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PET with 6-bromo-7-[<jats:sup>11<\/jats:sup>C]methylpurine ([<jats:sup>11<\/jats:sup>C]BMP) has been used to measure MRP1 function in rodents. In this study, [<jats:sup>11<\/jats:sup>C]BMP was for the first time characterised in humans to assess the function of MRP1 and other MRP subtypes in different tissues.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Thirteen healthy volunteers (7 men, 6 women) underwent dynamic whole-body PET scans on a long axial field-of-view (LAFOV) PET\/CT system after intravenous injection of [<jats:sup>11<\/jats:sup>C]BMP. Three subjects of each sex were scanned a second time to assess reproducibility. Volumes of interest were outlined for MRP-expressing tissues (cerebral cortex, cerebellum, choroid plexus, retina, lungs, myocardium, kidneys, and liver). From the time-activity curves, the elimination rate constant (<jats:italic>k<\/jats:italic><jats:sub>E<\/jats:sub>, h<jats:sup>\u2212\u20091<\/jats:sup>) was derived as a parameter for tissue MRP function and its test-retest variability (TRTV, %) was calculated. Radiation dosimetry was calculated using the Medical Internal Radiation Dose (MIRD) methodology.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mean <jats:italic>k<\/jats:italic><jats:sub>E<\/jats:sub> and corresponding TRTV values were: cerebral cortex: 0.055\u2009\u00b1\u20090.010\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (\u2212\u20094\u2009\u00b1\u200924%), cerebellum: 0.033\u2009\u00b1\u20090.009\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (1\u2009\u00b1\u200939%), choroid plexus: 0.292\u2009\u00b1\u20090.059\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (0.1\u2009\u00b1\u200916%), retina: 0.234\u2009\u00b1\u20090.045\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (30\u2009\u00b1\u200938%), lungs: 0.875\u2009\u00b1\u20090.095\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (\u2212\u20093\u2009\u00b1\u200911%), myocardium: 0.641\u2009\u00b1\u20090.105\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (11\u2009\u00b1\u200925%), kidneys: 1.378\u2009\u00b1\u20090.266\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (14\u2009\u00b1\u200916%), and liver: 0.685\u2009\u00b1\u20090.072\u00a0h<jats:sup>\u2212\u20091<\/jats:sup> (7\u2009\u00b1\u20099%). Significant sex differences were found for <jats:italic>k<\/jats:italic><jats:sub>E<\/jats:sub> in the cerebellum, lungs and kidneys. Effective dose was 4.67\u2009\u00b1\u20090.18 \u00b5Sv\/MBq for men and 4.55\u2009\u00b1\u20090.18 \u00b5Sv\/MBq for women.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>LAFOV PET\/CT with [<jats:sup>11<\/jats:sup>C]BMP potentially allows for simultaneous assessment of MRP function in multiple human tissues. Mean TRTV of <jats:italic>k<\/jats:italic><jats:sub>E<\/jats:sub> in different tissues was in an acceptable range, except for the retina. The radiation dosimetry of [<jats:sup>11<\/jats:sup>C]BMP was in the typical range of <jats:sup>11<\/jats:sup>C-tracers. LAFOV PET\/CT holds great potential to assess at a whole-body, multi-tissue level molecular targets relevant for drug disposition in humans.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>EudraCT 2021-006348-29. Registered 15 December 2021.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00259-024-06851-2","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T21:05:15Z","timestamp":1722027915000},"page":"3900-3911","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["First-in-human evaluation of 6-bromo-7-[11C]methylpurine, a PET tracer for assessing the function of multidrug resistance-associated proteins in different tissues"],"prefix":"10.1007","volume":"51","author":[{"given":"Severin","family":"Mairinger","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Jackwerth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zacharias","family":"Chalampalakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"W\u00f6lfl-Duchek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Pracher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Nics","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Pahnke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Langsteger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Hacker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Zeitlinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Langer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"6851_CR1","doi-asserted-by":"publisher","first-page":"30880","DOI":"10.1074\/jbc.R114.609248","volume":"289","author":"SP Cole","year":"2014","unstructured":"Cole SP. 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