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• W1509718835 abstract "Matrix metalloproteinases (MMPs) play a pivotal role in cancer progression and present therefore an interesting biomarker for early diagnosis, staging and therapy evaluation. Consequently, MMP-specific molecular imaging probes have been proposed for noninvasive visualization and quantification of MMP activity. An interesting approach is MMP-2/9 activatable cell-penetrating peptides (ACPP) that accumulate in the tumor tissue after activation. However, a recent study revealed that probe activation occurred already in the vasculature followed by nonspecific tumor targeting. In the latter study, biodistribution was determined 6 and 24 h post-ACPP injection. An alternative explanation could still be that the kinetics of tumor-specific activation is faster than that of blood activation plus subsequent nonspecific uptake in tumor. The aim of this study was to assess if tumor-specific ACPP activation occurs in mice with MMP-2/9 positive subcutaneous HT-1080 tumors at 3 h post-injection. As control, we studied the MMP-2/9 sensitive ACPP in mice bearing subcutaneous BT-20 tumors with low MMP-2/9 expression to test if probe cleavage correlates with tumoral MMP expression. Ex vivo biodistribution showed no improved tumoral ACPP activation in HT-1080 tumor-bearing mice at 3 h post-injection compared with previous reported data collected at 24 h post-injection. Furthermore, tumoral uptake and relative tumoral activation for ACPP were similar in both BT-20 and HT-1080 tumor-bearing mice. In conclusion, this study suggests that tumoral ACPP uptake in these tumor models originates from probe activation in the vasculature instead of tumor-specific MMP activation. Novel ACPPs that target tissue-specific proteases without nonspecific activation may unleash the full potential of the elegant ACPP concept." @default.
• W1509718835 created "2016-06-24" @default.
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• W1509718835 date "2014-05-13" @default.
• W1509718835 modified "2023-10-16" @default.
• W1509718835 title "<i>In vivo</i>biodistribution of radiolabeled MMP-2/9 activatable cell-penetrating peptide probes in tumor-bearing mice" @default.
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• W1509718835 doi "https://doi.org/10.1002/cmmi.1605" @default.
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