Serial monitoring of human systemic and xenograft models of leukemia using a novel vascular disrupting agent Journal Article
| Authors: | Benezra, M.; Phillips, E.; Tilki, D.; Ding, B. S.; Butler, J.; Dobrenkov, K.; Siim, B.; Chaplin, D.; Rafii, S.; Rabbany, S.; Bradbury, M. S. |
| Article Title: | Serial monitoring of human systemic and xenograft models of leukemia using a novel vascular disrupting agent |
| Abstract: | Advances in the treatment of acute leukemia have resulted in significantly improved remission rates, although disease relapse poses a significant risk. By utilizing sensitive, non-invasive imaging guidance, detection of early leukemic infiltration and the extent of residual tumor burden after targeted therapy can be expedited, leading to more efficient treatment planning. We demonstrated marked survival benefit and therapeutic efficacy of a new-generation vascular disrupting agent, combretastatin-A1-diphosphate (OXi4503), using reporter gene-imaging technologies and mice systemically administered luc and GFP human leukemic cells (LCs). Before treatment, homing of double-transduced cells was serially monitored and whole-body cellular distributions were mapped using bioluminescence imaging (BLI). Imaging findings strongly correlated with quantitative GFP expression levels in solid organs/tissues, suggesting that the measured BLI signal provides a highly sensitive and reliable biomarker of tumor tissue burden in systemic leukemic models. Such optical technologies can thereby serve as robust non-invasive imaging tools for preclinical drug discovery and for rapidly screening promising therapeutic agents to establish potency, treatment efficacy and survival advantage. We further show that GFP HL-60 cells reside in close proximity to VE-cadherin-and CD31-expressing endothelial cells, suggesting that the perivascular niche may have a critical role in the maintenance and survival of LCs. © 2012 Macmillan Publishers Limited. |
| Keywords: | cancer survival; controlled study; protein expression; leukemia; unclassified drug; human cell; drug efficacy; monotherapy; nonhuman; antineoplastic agents; cytarabine; monitoring; mouse; animals; mice; tumor volume; gfp; green fluorescent protein; luciferase; animal experiment; animal model; in vivo study; tumor xenograft; xenograft model antitumor assays; transduction, genetic; luminescent measurements; tumor burden; leukemia cell; combretastatin a4 phosphate; reporter gene; cell movement; cellular distribution; genes, reporter; vascular targeting agent; bioluminescence; cell tracking; cell homing; hl-60 cells; stilbenes; diphosphates; hl-60; oxi4503; combretastatin a1 diphosphate |
| Journal Title: | Leukemia |
| Volume: | 26 |
| Issue: | 8 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-08-01 |
| Start Page: | 1771 |
| End Page: | 1778 |
| Language: | English |
| DOI: | 10.1038/leu.2012.48 |
| PROVIDER: | scopus |
| PUBMED: | 22343591 |
| PMCID: | PMC4626450 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: LEUKE" - "Source: Scopus" |
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