ArticleBioactive materials2027
Preclinical evaluation of PSMA-targeted ultrasound contrast agents in an orthotopic model of prostate cancer in rabbits.
Article in Bioactive materials, 2027. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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 differentiating viable tumor, necrotic tissue, and margin-associated disease. We investigated prostate-specific membrane antigen (PSMA)-targeted lipid-shelled perfluorocarbon nanobubbles (PSMA-NBs) in an orthotopic rabbit model using a clinical contrast-enhanced ultrasound (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 Plain-NBs using identical protocols. To address tumor heterogeneity and ultrasound boundary ambiguity, regions of interest were defined from baseline B-mode images and segmented into the tumor core, rim, and a peritumoral area. Pixel-wise parametric and decorrelation time (DT) maps were generated and compared with whole-slide histology (H&E) and, in an exploratory and non-specific analysis, with PSMA IHC. Compared to MBs at the doses used, 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 [MTT]: 4.20 to 5.40-fold higher) for up to 10 min in the tumor and peritumoral areas. In an exploratory analysis constrained by cohort size, PSMA-NB kinetics, notably MTT, tracked histology-defined tumor viability, and DT mapping showed spatially heterogeneous retention at the tumor periphery. Compared to Plain-NBs, PSMA-NBs also exhibited improved retention (MTT +21% overall) in the rim and peritumoral areas. This study demonstrates the potential of PSMA-NBs to characterize prostate cancer by molecularly targeted CEUS beyond that achieved with MBs at the doses used.
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