**5. Conclusions**

A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation can produce GBq-scale <sup>165</sup>Er suitable for high-yield radiolabelings of DOTA-based radiopharmaceuticals at molar activities befitting investigations of targeted radionuclide therapeutics. The separation utilizes column chromatography with commercially available resins and is well suited for automation. This significant step forward in the production and high holmium/erbium SF radiochemical isolation of <sup>165</sup>Er will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals. Proof-ofconcept radiolabeling studies were successfully performed synthesizing [165Er]PSMA-617, which will be utilized in vitro and in vivo to understand the role of AEs in PSMA-targeted radionuclide therapy of prostate cancer.

**Supplementary Materials:** Supplementary Figures S1–S8, Supplementary Material Sections S1–S3, and Supplementary Equation (S1),

**Author Contributions:** Conceptualization, I.D.S., J.C.M., J.W.E. and P.A.E.; methodology, I.D.S., T.R.J., J.C.M., E.A.-S., T.E.B., R.J.N., J.W.E. and P.A.E.; validation, I.D.S., T.R.J., J.C.M. and P.A.E.; formal analysis, I.D.S., T.R.J., J.C.M. and P.A.E.; investigation, I.D.S., T.R.J. and J.C.M.; resources, R.J.N., T.E.B., J.W.E. and P.A.E.; data curation, I.D.S., T.R.J., J.C.M. and P.A.E.; writing—original draft preparation, I.D.S., T.R.J., J.C.M. and P.A.E.; writing—review and editing, I.D.S., T.R.J., J.C.M., E.A.-S., T.E.B., R.J.N., J.W.E. and P.A.E.; supervision, J.W.E. and P.A.E.; project administration, P.A.E.; funding acquisition, J.W.E. and P.A.E.; All authors have read and agreed to the published version of the manuscript.

**Funding:** Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number T32 CA009206 (J.C.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research is supported in part by the U.S. Department of Energy Isotope Program, managed by the Office of Science for Isotope R&D and Production, grant DE-SC0020955.

**Acknowledgments:** A portion of the LN2 resin used in this work was graciously provided by Triskem Int.

**Conflicts of Interest:** The authors declare no conflict of interest.
