{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:18:12Z","timestamp":1785417492013,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Telix Pharmaceuticals"},{"id":[{"id":"https:\/\/ror.org\/01memxq33","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Lutetium (177Lu) TLX591 (177Lu-TLX591) is a radio antibody\u2013drug conjugate (rADC) that utilizes a novel monoclonal antibody-based approach for treatment of patients with prostate-specific membrane antigen (PSMA)-expressing metastatic castration-resistant prostate cancer (mCRPC). ProstACT SELECT (NCT04786847) was a multicenter, single-arm, open-label Phase 1 trial evaluating patient selection for 177Lu-TLX591 therapy using 68Ga-PSMA-11 PSMA positron emission tomography (PET) in a heterogenous sample of patients with mCRPC. Primary and key secondary objectives were to evaluate safety and tolerability, biodistribution, and organ radiation dosimetry of 177Lu-TLX591 in combination with the best standard of care (SOC) for patients with PSMA-expressing mCRPC who progressed despite prior treatment with an androgen receptor pathway inhibitor. Methods: Thirty patients received 177Lu-TLX591 intravenously in combination with investigator-determined SOC. Cohort 1 (n = 5) received an imaging dose of 177Lu-TLX591 (1 GBq [27 mCi]), followed 14 days later by one therapeutic dose (2.8 GBq [76 mCi]). Cohort 2 received two therapeutic doses of 177Lu-TLX591, 14 days apart. Baseline 68Ga-PSMA-11 PET was performed to confirm eligibility and was qualitatively compared with serial 177Lu-TLX591 single-photon emission computed tomography (SPECT)\/CT, which was performed at five timepoints following the first 177Lu-TLX591 administration and also used to evaluate organ radiation dosimetry. Safety assessments included monitoring for treatment-emergent adverse events and collection of laboratory samples at specified timepoints used for biomarker analyses. Results: Tumor targeting observed on 177Lu-TLX591 SPECT\/CT imaging was qualitatively consistent with uptake observed on 68Ga-PSMA-11 PET imaging. No new safety signals were observed. Radiation exposure was within safety limits, with the highest absorbed dose to liver (clearance organ; 2.44 \u00b1 0.56 Gy\/GBq) and with lower exposure to salivary glands (0.07 \u00b1 0.03 Gy\/GBq) and kidneys (0.64 \u00b1 0.17 Gy\/GBq). Activity was retained in tumor lesions through to the final protocol-specified imaging timepoint (312 h) following administration. Conclusions: In this Phase 1, single-arm study, 68Ga-PSMA-11 PET supported patient selection for 177Lu-TLX591 therapy. In a heterogenous population representative of a real-world setting, 177Lu-TLX591 therapy in combination with SOC demonstrated a manageable and predictable safety profile, durable retention, and low salivary gland radiation exposure. Further evaluation in larger, randomized studies is warranted.<\/jats:p>","DOI":"10.3390\/cancers18142331","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:09:09Z","timestamp":1784527749000},"page":"2331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Theranostic Potential of 177Lu-TLX591 with Best Standard-of-Care and 68Ga-PSMA-11 PET for Patients with Metastatic Castration-Resistant Prostate Cancer: Results from the Phase 1 ProstACT SELECT Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-8766","authenticated-orcid":false,"given":"Nat","family":"Lenzo","sequence":"first","affiliation":[{"name":"GenesisCare, Alexandria, NSW 2015, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"O\u2019Byrne","sequence":"additional","affiliation":[{"name":"Medical Oncology, Princess Alexandra Hospital, Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Ngai","sequence":"additional","affiliation":[{"name":"Medical Oncology, Princess Alexandra Hospital, Translational Research Institute, Queensland University of Technology, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Krieger","sequence":"additional","affiliation":[{"name":"GenesisCare, St Leonards (North Shore Health Hub), St Leonards, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Wong","sequence":"additional","affiliation":[{"name":"Nepean Blue Mountains Local Health District Hospital, Penrith, NSW 2750, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Cade","sequence":"additional","affiliation":[{"name":"Telix Pharmaceuticals, North Melbourne, VIC 3051, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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