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Melanocortin-1 receptor (MC1R) is a promising target for radionuclide therapy of metastatic melanoma, and alpha-melanocyte stimulating hormone (\u03b1-MSH) peptide analogs show high affinities to MC1Rs. Because targeted alpha therapy (TAT) can be a desirable treatment for metastatic melanoma, this study aimed to develop an <jats:sup>211<\/jats:sup>At-labeled \u03b1-MSH peptide analog for TAT of metastatic melanoma.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We designed an \u03b1-MSH analog labeled with <jats:sup>211<\/jats:sup>At using a\u00a0neopentyl glycol scaffold via a hydrophilic linker. Preliminary studies using <jats:sup>125<\/jats:sup>I-labeled \u03b1-MSH analogs were performed to identify suitable hydrophilic linkers. Then, [<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> was prepared using a procedure similar to that of the <jats:sup>125<\/jats:sup>I-labeled counterpart, [<jats:sup>125<\/jats:sup>I]NpG-GGN<jats:bold>4b<\/jats:bold>. The biodistribution profile of [<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> in B16F10 tumor-bearing mice was compared with that of [<jats:sup>125<\/jats:sup>I]NpG-GGN<jats:bold>4b<\/jats:bold>. B16F10 tumor-bearing mice were treated with a single dose of vehicle or [<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> (1 or 0.4 MBq<jats:bold>)<\/jats:bold>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The D-Glu-D-Arg linker was identified as the optimal hydrophilic linker because of its high affinity for MC1R and good biodistribution profile, especially with low accumulation in the liver and intestine. [<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> showed tumor accumulation comparable to that of [<jats:sup>125<\/jats:sup>I]NpG-GGN<jats:bold>4b<\/jats:bold> and maintained the tumor radioactivity retention from 1 to 3\u00a0h postinjection. [<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> exhibited a dose-dependent inhibitory effect on B16F10 xenograft growth without apparent body weight loss.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>[<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> showed dose-dependent efficacy against B16F10 xenografts, suggesting that [<jats:sup>211<\/jats:sup>At]NpG-GGN<jats:bold>4c<\/jats:bold> is a promising TAT agent for treating metastatic melanoma.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00259-024-07056-3","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T03:02:56Z","timestamp":1737342176000},"page":"2107-2117","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["An 211At-labeled alpha-melanocyte stimulating hormone peptide analog for targeted alpha therapy of metastatic melanoma"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-4274","authenticated-orcid":false,"given":"Hiroyuki","family":"Suzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5919-1820","authenticated-orcid":false,"given":"Kento","family":"Kannaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ohshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-8580","authenticated-orcid":false,"given":"Shigeki","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-027X","authenticated-orcid":false,"given":"Kazuhiro","family":"Ooe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-2395","authenticated-orcid":false,"given":"Tadashi","family":"Watabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko S.","family":"Ishioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3661-9310","authenticated-orcid":false,"given":"Hiroshi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-9800","authenticated-orcid":false,"given":"Tomoya","family":"Uehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"issue":"7","key":"7056_CR1","doi-asserted-by":"publisher","first-page":"3474","DOI":"10.3390\/ijms22073474","volume":"22","author":"M Ottaviano","year":"2021","unstructured":"Ottaviano M, Giunta EF, Tortora M, Curvietto M, Attademo L, Bosso D, et al. 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