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Various strategies to mitigate this side effect have been attempted with limited success. Accordingly, this study introduced a new PSMA-targeting ligand with more favorable binding characteristics than the existing ligands.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      The binding affinity of PSMA-1-DOTA to PSMA was compared with that of PSMA-11 and PSMA I&amp;T. Comparison of uptake in the salivary glands, kidneys and PC3pip tumor cells in the xenograft mouse models between [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]Ga-PSMA-1-DOTA, [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]Ga-PSMA-11 and [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]Ga-PSMA I&amp;T was conducted with microPET\/CT within the same week. The same mouse models were treated with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-PSMA-1-DOTA or [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-PSMA-617. A compassionate use PET imaging study on a patient with metastatic castration-resistant prostate cancer was performed using [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]Ga-PSMA-1-DOTA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The binding affinity of PSMA-1-DOTA to PSMA was found to be approximately four times greater than other PSMA-targeted ligands. Imaging with microPET\/CT revealed significantly lower kidney, uptake and little salivary and lacrimal gland uptake with [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]Ga-PSMA-1-DOTA compared to other PSMA-radioligands. Preclinical efficacy studies demonstrated that [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-PSMA-1-DOTA inhibited tumor growth comparable to that with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-PSMA-617, suggesting its potential to enhance the therapeutic window of targeted RLT by avoiding damage to the salivary glands. The compassionate use PET imaging confirmed the reduced salivary gland uptake of [\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga]Ga-PSMA-1-DOTA in the patient, indicating its potential utility as a targeting agent for RLT with \u03b1- or \u03b2-emitting radionuclides in patients with PSMA-positive prostate cancer.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PSMA-1-DOTA shows reduced uptake in salivary glands while effectively targeting PSMA-expressing tumors, thus potentially avoiding the side effects of xerostomia, and possibly moving PSMA-targeted RLT to a more frontline therapy for prostate cancer rather than the current use as a last resort.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-025-02046-9","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T16:18:42Z","timestamp":1756829922000},"page":"785-796","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PSMA-1-DOTA Potentially for Effective Targeted Radioligand Therapy of Prostate Cancer"],"prefix":"10.1007","volume":"27","author":[{"given":"Xinning","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"sergeeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim","family":"Sergeev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoey","family":"Lockwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Wojtylak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riley","family":"Sangster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Reichert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Berridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2429-9911","authenticated-orcid":false,"given":"Zhenghong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Basilion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"issue":"12","key":"2046_CR1","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.2967\/jnumed.116.178673","volume":"57","author":"C Kratochwil","year":"2016","unstructured":"Kratochwil C, Bruchertseifer F, Giesel FL et al (2016) 225Ac-PSMA-617 for PSMA-Targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer. 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