{"doi":"10.1101/2020.09.11.294264","title":"PSA-targeted Alpha-, Beta- and Positron Emitting Immuno-Theranostics in Murine Prostate Cancer Models and Non-Human Primates","abstract":"ABSTRACT Purpose Most prostate cancer (PCa) patients treated with androgen receptor (AR)-signaling inhibitors develop therapeutic resistance due to restoration of AR-functionality. Thus, there is a critical need for novel treatment approaches. Here we investigate the theranostic potential of hu5A10, a humanized monoclonal antibody specifically targeting free prostate-specific antigen ( KLK3 ). Experimental Design LNCaP-AR xenografts (NSG mice) and KLK3 _Hi- Myc transgenic mice were imaged with 89 Zr- or treated with 90 Y- or 225 Ac-labeled hu5A10; biodistribution and subcellular localization were analyzed by gamma-counting, positron emission tomography (PET), autoradiography and microscopy. Therapeutic efficacy of [ 225 Ac]hu5A10 and [ 90 Y]hu5A10 in LNCaP-AR tumors was assessed by tumor volume measurements, time to nadir (TTN), time to progression (TTP), and survival. Pharmacokinetics of [ 89 Zr]hu5A10 in non-human primates (NHP) were determined using PET. Results Biodistribution of radiolabeled hu5A10-constructs was comparable in different mouse models. Specific tumor uptake increased over time and correlated with PSA expression. Treatment with [ 90 Y]/[ 225 Ac]hu5A10 effectively reduced tumor burden and prolonged survival (p≤0.0054). Effects of [ 90 Y]hu5A10 were more immediate than [ 225 Ac]hu5A10 (TTN, p<0.0001) but less sustained (TTP, p<0.0001). Complete responses were observed in 7/18 [ 225 Ac]hu5A10 and 1/9 mice [ 90 Y]hu5A10. Pharmacokinetics of [ 89 Zr]hu5A10 were consistent between NHPs and comparable to those in mice. [ 89 Zr]hu5A10-PET visualized the NHP-prostate over the 2-week observation period. Conclusions We present a complete preclinical evaluation of radiolabeled hu5A10 in mouse PCa models and NHPs, and establish hu5A10 as a new theranostic agent that allows highly specific and effective downstream targeting of AR in PSA-expressing tissue. Our data support the clinical translation of radiolabeled hu5A10 for treating PCa.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124030,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":567773,"name":"Claire M. Storey","orcid":"0000-0003-0792-1569","position":1,"is_corresponding":false},{"id":568215,"name":"Katharina Lückerath","orcid":null,"position":2,"is_corresponding":false},{"id":568216,"name":"Katharina Braun","orcid":null,"position":3,"is_corresponding":false},{"id":568217,"name":"Christian von Bodman","orcid":null,"position":4,"is_corresponding":false},{"id":567774,"name":"Urpo Lamminmäki","orcid":"0000-0002-6336-1407","position":5,"is_corresponding":false},{"id":451222,"name":"Teja Kalidindi","orcid":"0000-0002-0210-0270","position":6,"is_corresponding":false},{"id":567775,"name":"Sven‐Erik Strand","orcid":"0000-0001-5343-0213","position":7,"is_corresponding":false},{"id":568218,"name":"Joanna Strand","orcid":null,"position":8,"is_corresponding":false},{"id":567776,"name":"Mohamed Altai","orcid":"0000-0002-7624-0313","position":9,"is_corresponding":false},{"id":266371,"name":"Robert Damoiseaux","orcid":"0000-0002-7611-7534","position":10,"is_corresponding":false},{"id":345009,"name":"Pat Zanzonico","orcid":"0000-0002-7334-2752","position":11,"is_corresponding":false},{"id":503018,"name":"Nadia Benabdallah","orcid":"0000-0002-1511-6693","position":12,"is_corresponding":false},{"id":345815,"name":"Dmitry Pankov","orcid":"0000-0002-2262-9294","position":13,"is_corresponding":false},{"id":90756,"name":"Howard I. Scher","orcid":"0000-0002-6791-9324","position":14,"is_corresponding":false},{"id":442372,"name":"Peter T. Scardino","orcid":"0000-0002-1601-8411","position":15,"is_corresponding":false},{"id":424346,"name":"Steven M. Larson","orcid":"0000-0002-6111-7507","position":16,"is_corresponding":false},{"id":350626,"name":"Hans Lilja","orcid":"0000-0001-5871-7846","position":17,"is_corresponding":false},{"id":107711,"name":"Michael R. McDevitt","orcid":"0000-0002-8855-0917","position":18,"is_corresponding":false},{"id":503022,"name":"Daniel L.J. Thorek","orcid":"0000-0003-2437-1239","position":19,"is_corresponding":false},{"id":535215,"name":"David Ulmert","orcid":"0000-0002-7871-2281","position":20,"is_corresponding":false},{"id":567772,"name":"Darren R. Veach","orcid":"0000-0002-8201-622X","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}