Quantification of extravasation and binding of PSMA-targeted nanobubbles by modelling the second-wave phenomenon
© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Molecular imaging and biology - 26(2024), 2 vom: 27. März, Seite 253-263 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Chuan [VerfasserIn] |
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| Links: |
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| Themen: |
Contrast Media |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 28.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s11307-023-01891-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Chen, Chuan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Quantification of extravasation and binding of PSMA-targeted nanobubbles by modelling the second-wave phenomenon |
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| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to World Molecular Imaging Society. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Contrast-enhanced ultrasound | |
| 650 | 4 | |a Molecular imaging | |
| 650 | 4 | |a Nanobubbles | |
| 650 | 4 | |a Prostate cancer | |
| 650 | 4 | |a Second-wave phenomenon | |
| 650 | 7 | |a Contrast Media |2 NLM | |
| 700 | 1 | |a Perera, Reshani |e verfasserin |4 aut | |
| 700 | 1 | |a Mischi, Massimo |e verfasserin |4 aut | |
| 700 | 1 | |a Kolios, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Exner, Agata |e verfasserin |4 aut | |
| 700 | 1 | |a Turco, Simona |e verfasserin |4 aut | |
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