Samenvatting
Purpose: With about ten-fold smaller diameter than MBs, nanobubbles (NBs) were developed as new-generation ultrasound contrast agents (UCA) able to extravasate and target specific receptors expressed on extravascular cancer cells, such as the prostate-specific membrane antigen (PSMA). It has been shown that PSMA-targeted NBs (PSMA-NBs) can bind to specific prostate cancer (PCa) cells and exhibit a prolonged retention effect (PRE), observable by NB-based CEUS (NB-CEUS). However, previous analyses of PRE were mainly limited to the semi-quantitative assessment of the time-intensity curve (TIC) in an entire tumor ROI, possibly losing information on tumor spatial heterogeneity and local characteristics. When analyzing the pixel-level TICs of free NB-based CEUS, we observed a unique second-wave phenomenon: The first pass of the NB wave (bolus) is usually accompanied by a second wave in the time range of 3 to 15 min after the bolus injection. Such a phenomenon was shown to be potentially valuable in supporting the diagnostics of cancerous lesions. Procedures: Seven male athymic nude mice were included and implanted with a tumor expressing PSMA (PSMA+) and tumors not expressing PSMA (PSMA-) on two flanks. Using either free NBs or PSMA-NBs, the characteristics of pixel-level TICs were estimated by a specialized model accounting for the two-wave phenomenon, compared with a conventional model describing only one wave. The estimated parameters by the two models were presented as parametric maps to visualize the PRE of PSMA-NBs in a dual-tumor mouse model. The effectiveness of the two models were also assessed by comparing the estimated parameters in the PSMA+ and PSMA- tumors through Mann-Whitney U test and quartile difference. Results: Two parameters, the peak time and residual factor of the second wave, by the second-wave model were significantly different between PSMA+ and PSMA- tumors when using PSMA-NBs. Compared with the TICs of free NBs, TICs of PSMA-NBs present higher peak intensity and a more delayed second wave, especially in the PSMA+ tumor. Conclusions: The estimation of parametric maps allows the estimation and visualization of specific binding of PSMA-NBs in PCa. The incorporation of the second-wave phenomenon enrich our understanding of NB kinetics in vivo and can possibly contribute to improved diagnostics of PCa in the future.
Originele taal-2 | Engels |
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Pagina's (van-tot) | 253-263 |
Aantal pagina's | 11 |
Tijdschrift | Molecular Imaging and Biology |
Volume | 26 |
Nummer van het tijdschrift | 2 |
DOI's | |
Status | Gepubliceerd - apr. 2024 |
Financiering
This work was funded by the National Institutes of Health (R01EB028144), 1S10OD021635-01, the CWRU Coulter Translational Research Partnership, and the 4TU. Precision Medicine grant.
Financiers | Financiernummer |
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National Institutes of Health, NIH | 1S10OD021635-01, R01EB028144 |