biostudies-literatureTafreshi NKNational Cancer InstituteNCI NIH HHSNeuroendocrine Tumor Research FoundationH. Lee Moffitt Cancer Center and Research Institute3408-3421https://www.ebi.ac.uk/biostudies/studies/S-EPMC12866175biostudies-literatureUnknown48(11)<h4>Purpose</h4>There is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the β-particle emitting radionuclide ¹⁷⁷Lu ([¹⁷⁷Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [²²⁵Ac]Ac-DOTA-TATE in patients that were refractory to [¹⁷⁷Lu]Lu-DOTA-TATE. Herein, we report the radiosynthesis, toxicity, biodistribution (BD), radiation dosimetry (RD), and efficacy of [²²⁵Ac]Ac-DOTA-TATE in small animal models of lung neuroendocrine neoplasms (NENs).<h4>Methods</h4>[²²⁵Ac]AcEuropean journal of nuclear medicine and molecular imagingPreclinical evaluation of [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms.PMC12866175P30-CA076292P30 CA076292Tichacek CJEl-Haddad GJi HChiappori AAPandya DNStrosberg JRBudzevich MMBoulware DCEngelman RWTafreshi NKReff JNWadas TJWang ZMorse DLfalsePreclinical evaluation of [&lt;sup&gt;225&lt;/sup&gt;Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms.<h4>Purpose</h4>There is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the β-particle emitting radionuclide ¹⁷⁷Lu ([¹⁷⁷Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [²²⁵Ac]Ac-DOTA-TATE in patients that were refractory to [¹⁷⁷Lu]Lu-DOTA-TATE. Herein, we report the radiosynthesis, toxicity, biodistribution (BD), radiation dosimetry (RD), and efficacy of [²²⁵Ac]Ac-DOTA-TATE in small animal models of lung neuroendocrine neoplasms (NENs).<h4>Methods</h4>[²²⁵Ac]Ac2021-01-01T00:00:00Z2021 Oct2026-07-15T07:40:47.693Z2026-07-01T03:07:58.317ZS-EPMC128661753377233210.1007/s00259-021-05315-1