{"id":10220,"date":"2026-05-11T20:18:32","date_gmt":"2026-05-11T18:18:32","guid":{"rendered":"https:\/\/www.m2olie.de\/?post_type=publications&#038;p=10220"},"modified":"2026-06-20T20:24:10","modified_gmt":"2026-06-20T18:24:10","slug":"macropa-scaffold-expansion-for-actinium-225-chelation-a-synthetic-strategy-labeling-kinetics-and-theoretical-calculations","status":"publish","type":"publications","link":"https:\/\/www.m2olie.de\/en\/publications\/macropa-scaffold-expansion-for-actinium-225-chelation-a-synthetic-strategy-labeling-kinetics-and-theoretical-calculations\/","title":{"rendered":"Macropa Scaffold Expansion for Actinium-225 Chelation: A Synthetic Strategy, Labeling Kinetics, and Theoretical Calculations"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Baier NF, Cieslik P, Rudolf H, Pretze M, W\u00e4ngler B, Schirrmacher R, Greb L, Fricker G, Varga Z, Kov\u00e1cs A*, W\u00e4ngler C* (2026) Macropa Scaffold Expansion for Actinium-225 Chelation: Synthetic Strategy, Labeling Kinetics, and Theoretical Calculations. <em>Inorganic Chemistry, 65(18)<\/em>, 9769\u20139786.<br><strong>DOI:\u00a0<\/strong><a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.inorgchem.5c05424\" target=\"_blank\" rel=\"noreferrer noopener\">10.1021\/acs.inorgchem.5c05424.<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>\u00a0<\/strong><sup>225<\/sup>Ac is a key \u03b1-emitter for targeted alpha therapy. Among available chelators, Macropa currently provides some of the most stable\u00a0<sup>225<\/sup>Ac complexes, yet the limited stability of [<sup>225<\/sup>Ac]Ac-Macropa indicates a further optimization potential. Here, we report the design and evaluation of a new Ac<sup>3+<\/sup>\u00a0chelator, coined Megapa, and assessed its suitability to produce stably labeled\u00a0<sup>225<\/sup>Ac-based radiopharmaceuticals using radiochemical and computational methods. Unexpectedly, Megapa showed poorer radiolabeling performance than Macropa, showing reduced\u00a0<sup>225<\/sup>Ac incorporation (80.2 \u00b1 2.9% RCC vs quantitative labeling) across multiple conditions tested. In addition, [<sup>225<\/sup>Ac]Ac-Megapa displayed lower kinetic inertness than [<sup>225<\/sup>Ac]Ac-Macropa, with lower stability in human serum (45.8% intact after 7 days vs no detectable degradation) and substantially higher\u00a0<sup>225<\/sup>Ac release in La<sup>3+<\/sup>\u00a0challenge experiments (64.3% vs 0.7%). Thermodynamic stability studies supported these results, indicating a lower thermodynamic stability of La-Megapa compared to La-Macropa (log\u00a0<em>K<\/em><sub>LaL<\/sub>\u00a0of 10.53 vs 13.90). To rationalize these findings, quantum chemical calculations were performed on the Ac<sup>3+<\/sup>\u00a0and La<sup>3+<\/sup>\u00a0complexes of Megapa and Macropa. The computed low-energy structures were closely analogous for both chelators, indicating that the differing radiochemical behavior is unlikely to arise from intrinsic metal-ligand bonding. Instead, solvation effects and solution-phase molecular interactions are the most probable contributors to the poorer performance of Megapa.<\/p>\n","protected":false},"featured_media":0,"comment_status":"open","ping_status":"closed","template":"","meta":{"footnotes":""},"categories":[],"class_list":["post-10220","publications","type-publications","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/10220","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications"}],"about":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/types\/publications"}],"replies":[{"embeddable":true,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/comments?post=10220"}],"version-history":[{"count":1,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/10220\/revisions"}],"predecessor-version":[{"id":10221,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/publications\/10220\/revisions\/10221"}],"wp:attachment":[{"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/media?parent=10220"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.m2olie.de\/en\/wp-json\/wp\/v2\/categories?post=10220"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}