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[\n                      <jats:sup>11<\/jats:sup>\n                      C]trimethoprim ([\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP) is a positron emission tomography (PET) imaging isotopologue of TMP. TMP binds with 30,000-fold greater affinity to bacterial DHFR over the homologous mammalian enzyme\n                      <jats:italic>in vitro<\/jats:italic>\n                      , suggesting [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP may selectively accumulate in tissues with cells expressing bacterial DHFR. This study characterizes the biodistribution and dosimetry of [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP, informing its use in imaging bacterial infections and tracking mammalian cells expressing eDHFR as a reporter gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Four males with suspected infection, aged 59\u2009\u00b1\u200910\u00a0years old (mean\u2009\u00b1\u2009SD) received 3 serial PET\/CT scans after injection of 346\u2009\u00b1\u2009305\u00a0MBq (range 129\u2013797\u00a0MBq) of [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP. Organ activities were measured in MIM v6.7, including brain, kidneys, spleen, liver, heart, lungs, bladder, intestines, gallbladder, pancreas, thyroid, and red marrow. Dosimetry calculations were performed in Olinda | EXM v1.1. Additionally, a dynamic whole-body PET\/CT scan was performed on a separate participant. The associated trial was registered as NCT03424525.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP injections were well tolerated with no adverse events. The average injected activity of 346\u00a0MBq of [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP yielded an estimated average dose of 4.9\u00a0mSv in the highest uptake organ (liver), 4.1\u00a0mSv in the spleen, and an effective dose of 1.6\u00a0mSv. Suspected sites of infection displayed uptake above background.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP PET was safe and demonstrated low background uptake in most tissues. The data suggests feasibility for evaluation of varied bacterial infections, including musculoskeletal infections. Absorbed doses allow multiple [\n                      <jats:sup>11<\/jats:sup>\n                      C]TMP PET scans each year within Radioactive Drug Research Committee (RDRC) limits, potentially enabling monitoring of infections and treatment response.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-025-02064-7","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T23:21:36Z","timestamp":1763853696000},"page":"60-67","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["First-in-Human Biodistribution and Dosimetry of [11C]Trimethoprim"],"prefix":"10.1007","volume":"28","author":[{"given":"Anthony J.","family":"Young","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert K.","family":"Doot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua K.","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan M.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro A.","family":"Ordonez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres F.","family":"del Castillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany L.","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Supritha","family":"Dugyala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin K.","family":"Schubert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiaoju","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin R.","family":"Pantel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Mach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Mankoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-1905","authenticated-orcid":false,"given":"Mark A.","family":"Sellmyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"2064_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225808","volume":"20","author":"JD Northrup","year":"2019","unstructured":"Northrup JD, Mach RH, Sellmyer MA (2019) Radiochemical approaches to imaging bacterial infections: intracellular versus extracellular targets. 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Subjects also provided informed consent for publication of their radiographic images. The full study protocols are available at clinicaltrials.gov, NCT03424525 and were performed under the authority of the University of Pennsylvania Radioactive Drug Research Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"M.A.S., D.A.M., and R.H.M. have filed US patent US20180104365A1 assigned to the University of Pennsylvania on radiotracer derivatives of trimethoprim for medical imaging. M.A.S. and R.H.M. hold equity in Vellum Biosciences, a corporate entity which is commercializing TMP radiotracers.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}