PARPi-FL - A fluorescent PARP1 inhibitor for glioblastoma imaging Journal Article
| Authors: | Irwin, C. P.; Portorreal, Y.; Brand, C.; Zhang, Y.; Desai, P.; Salinas, B.; Weber, W. A.; Reiner, T. |
| Article Title: | PARPi-FL - A fluorescent PARP1 inhibitor for glioblastoma imaging |
| Abstract: | New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic. © 2014 Neoplasia Press, Inc. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; cancer localization; drug penetration; nonhuman; mouse; animal tissue; cell survival; fluorescent dye; animal experiment; animal model; in vivo study; drug structure; in vitro study; tumor xenograft; drug distribution; tissue distribution; glioblastoma; western blotting; cancer size; toxicity testing; drug tissue level; drug metabolism; high performance liquid chromatography; drug cytotoxicity; drug half life; image processing; drug binding; drug stability; fluorescence imaging; olaparib; drug degradation; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; hydrophobicity; reversed phase high performance liquid chromatography; plasma half life; time lapse imaging; human; priority journal; article; plasma protein binding; ic50; parpi fl; fluorescence imaging system; glioblastoma cell line; metabolic stability |
| Journal Title: | NeoPlasia |
| Volume: | 16 |
| Issue: | 5 |
| ISSN: | 1522-8002 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2014-05-01 |
| Start Page: | 432 |
| End Page: | 440 |
| Language: | English |
| DOI: | 10.1016/j.neo.2014.05.005 |
| PROVIDER: | scopus |
| PMCID: | PMC4198695 |
| PUBMED: | 24970386 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
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