{"doi":"10.1101/2025.08.07.668901","title":"Preclinical Evaluation of PSMA-Targeted Ultrasound Contrast Agents in an Orthotopic Model of Prostate Cancer in Rabbits","abstract":"The localization of prostate cancer by ultrasound remains limited by the lack of B-mode conspicuity and the confinement of clinically approved microbubbles (MBs) to the vasculature. This precludes the differentiation of viable tumor tissue, necrotic tissue, and margin-associated disease. We investigate the use of prostate-specific membrane antigen (PSMA)-targeted lipid-shelled perfluorocarbon nanobubbles (PSMA-NBs) in an orthotopic rabbit model using a clinical CEUS system. We implanted PSMA-positive PC3pip-GFP tumors into the prostates of immunosuppressed New Zealand White rabbits and performed transabdominal imaging with PSMA-NBs, MBs, and untargeted nanobubbles (Plain-NB) using the same imaging and analysis protocols. To address tumor heterogeneity and ultrasound boundary ambiguity, ROIs were defined from baseline B-mode images and segmented into the tumor core, rim, and a surrounding peritumoral area. Pixel-wise parametric and decorrelation time (DT) maps were generated and correlated with whole-slide histology (H&E) and PSMA IHC. Compared to MBs, PSMA-NBs exhibited higher peak intensities in the tumor core and rim (1.60-fold and 1.50-fold, respectively) and improved retention (mean transit time: 4.20 to 4.50-fold higher) for up to 10 minutes in the tumor and peritumoral areas. PSMA-NB kinetic and DT parameters also correlated with histology-defined tumor viability and PSMA expression. Compared to Plain-NBs, PSMA-NBs also exhibited improved retention (MTT +21%; AUCwo) in the rim and peritumoral areas. This study demonstrates the capability of PSMA-NBs to characterize prostate cancer by molecular CEUS beyond what is possible with conventional MBs.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558769,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":296389,"name":"Eric Abenojar","orcid":"0000-0002-2733-4006","position":1,"is_corresponding":false},{"id":486059,"name":"Pinunta Nittayacharn","orcid":"0000-0003-1114-4328","position":2,"is_corresponding":false},{"id":1052010,"name":"Nathan K. Hoggard","orcid":"0000-0003-2202-7506","position":3,"is_corresponding":false},{"id":1459571,"name":"Sidhartha Tavri","orcid":"0000-0003-4813-1790","position":4,"is_corresponding":false},{"id":1459572,"name":"Jing Wang","orcid":"0000-0003-4186-5388","position":5,"is_corresponding":false},{"id":1459573,"name":"Felipe Matsunaga","orcid":"0000-0002-0798-7632","position":6,"is_corresponding":false},{"id":988484,"name":"Michaela B. Cooley","orcid":"0000-0002-7955-3745","position":7,"is_corresponding":false},{"id":486060,"name":"Dana Wegierak","orcid":"0000-0003-1758-2417","position":8,"is_corresponding":false},{"id":296387,"name":"Xinning Wang","orcid":"0000-0001-7729-0534","position":9,"is_corresponding":false},{"id":514761,"name":"Thomas J. Rosol","orcid":"0000-0003-3737-1190","position":10,"is_corresponding":false},{"id":826347,"name":"James P. Basilion","orcid":"0000-0002-8659-3307","position":11,"is_corresponding":false},{"id":296390,"name":"Agata A. Exner","orcid":"0000-0003-3913-7066","position":12,"is_corresponding":false},{"id":1172802,"name":"Felipe M. Berg","orcid":"0000-0001-6028-2503","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"42146689","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":[]}