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As a late lanthanide, <jats:sup>165<\/jats:sup>Er is easy to label and can be used as a surrogate for other lanthanides or Ac in proof-of-concept studies. In this report, we explore the radiochemistry, in vitro, and in vivo behavior of [<jats:sup>165<\/jats:sup>Er]ErCl<jats:sub>3<\/jats:sub> and [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 to showcase the application of this radionuclide. Particularly, we report the first phantom and preclinical SPECT imaging of this radionuclide leveraging its characteristic X-ray photon emissions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The <jats:sup>165<\/jats:sup>Ho(p,n)<jats:sup>165<\/jats:sup>Er nuclear reaction using a 13 MeV cyclotron demonstrated production yields of up to 25\u2009\u00b1\u20095\u00a0MBq. \u00b5A<jats:sup>\u22121<\/jats:sup>\u00a0h<jats:sup>\u22121<\/jats:sup> at the end of the bombardment. After the purification (4.0\u2009\u00b1\u20090.5 h) using a sequential combination of cation exchange and extraction chromatography, 4-h irradiation produced up to 1.5 GBq of [<jats:sup>165<\/jats:sup>Er]ErCl<jats:sub>3<\/jats:sub>. High molar activity [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 was prepared (~\u2009200\u00a0MBq\/nmol). [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 showed a Log<jats:italic>D<\/jats:italic><jats:sub>7.4<\/jats:sub> value of -2.34\u2009\u00b1\u20090.24 meaning high hydrophilicity of the complex as expected. The stability of [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 in saline, human, and mouse serum was studied and showed intact tracer after 12 h in all three cases. [<jats:sup>165<\/jats:sup>Er]ErCl<jats:sub>3<\/jats:sub> and [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 were both taken up by LNCaP cells. PSMA-617 has IC<jats:sub>50<\/jats:sub> at nanomolar range for [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 in LNCaP cells. SPECT images with preclinical phantoms showed good uniformity, spatial resolution, and quantitative accuracy. SPECT\/CT imaging in LNCaP tumor-bearing mice injected with [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 showed high tumor uptake and quantitative accuracy when comparing the results to ex vivo biodistribution %IA\/g values. Mice injected with [<jats:sup>165<\/jats:sup>Er]ErCl<jats:sub>3<\/jats:sub> showed uptake in bone structures and excretion through both liver and kidneys.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study demonstrated the preclinical use of <jats:sup>165<\/jats:sup>Er for the first time. Using [<jats:sup>165<\/jats:sup>Er]ErCl<jats:sub>3<\/jats:sub> and [<jats:sup>165<\/jats:sup>Er]Er-PSMA-617 as examples, the radiochemistry, cell, and animal studies showed that <jats:sup>165<\/jats:sup>Er can be used as a tool for evaluating targeted radiopharmaceuticals. The X-ray emission from <jats:sup>165<\/jats:sup>Er can be used for quantitative SPECT imaging in mice.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s41181-024-00312-9","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T15:37:56Z","timestamp":1734536276000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["First preclinical SPECT\/CT imaging and biodistribution of [165Er]ErCl3 and [165Er]Er-PSMA-617"],"prefix":"10.1186","volume":"9","author":[{"given":"Behrad","family":"Saeedi Saghez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Rodr\u00edguez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Luis","family":"Esquinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Merkens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"B\u00e9nard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Radchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1833-9515","authenticated-orcid":false,"given":"Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"312_CR1","doi-asserted-by":"publisher","first-page":"10658","DOI":"10.1038\/s41598-019-47137-0","volume":"9","author":"E Aluicio-Sarduy","year":"2019","unstructured":"Aluicio-Sarduy E, Hernandez R, Olson AP, et al. 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