{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:13:40Z","timestamp":1790878420769,"version":"4.1.0"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Advanced Clinical Research Center management business subsidy from the Japanese government"},{"DOI":"10.13039\/100009619","name":"apan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ck0106815h0001"],"award-info":[{"award-number":["23ck0106815h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nPheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131<\/jats:sup>I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211<\/jats:sup>At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nWe are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211<\/jats:sup>At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123<\/jats:sup>I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211<\/jats:sup>At] MABG is 0.65 MBq\/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211<\/jats:sup>At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123<\/jats:sup>I] MIBG scintigraphy on reducing tumor accumulation, and quality of life.<\/jats:p>\n<\/jats:sec>\n\nTrials registration<\/jats:title>\njRCT2021220012<\/jats:ext-link> registered on 17 June 2022.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0303623","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T17:56:51Z","timestamp":1716919011000},"page":"e0303623","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Evaluation of pharmacokinetics, safety, and efficacy of [211At] meta-astatobenzylguanidine ([211At] MABG) in patients with pheochromocytoma or paraganglioma (PPGL): A study protocol"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5532-7364","authenticated-orcid":true,"given":"Masao","family":"Kobayakawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Shiga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyasu","family":"Sugawara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-3458","authenticated-orcid":true,"given":"Kaori","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Hanada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishizuka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"issue":"12","key":"pone.0303623.ref001","first-page":"802","article-title":"Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979","volume":"58","author":"CM Beard","year":"1983","journal-title":"Mayo Clin Proc"},{"issue":"3","key":"pone.0303623.ref002","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.0954-6820.1986.tb02755.x","article-title":"Pheochromocytoma in Sweden 1958\u20131981. 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