Molecular imaging of Akt kinase activity Journal Article
| Authors: | Zhang, L.; Lee, K. C.; Bhojani, M. S.; Khan, A. P.; Shilman, A.; Holland, E. C.; Ross, B. D.; Rehemtulla, A. |
| Article Title: | Molecular imaging of Akt kinase activity |
| Abstract: | The serine/threonine kinase Akt mediates mitogenic and anti-apoptotic responses that result from activation of multiple signaling cascades. It is considered a key determinant of tumor aggressiveness and is a major target for anticancer drug development. Here, we describe a new reporter molecule whose bioluminescence activity within live cells and in mice can be used to measure Akt activity. Akt activity in cultured cells and tumor xenografts was monitored quantitatively and dynamically in response to activation or inhibition of receptor tyrosine kinase, inhibition of phosphoinositide 3-kinase, or direct inhibition of Akt. The results provide unique insights into the pharmacokinetics and pharmacodynamics of agents that modulate Akt activity, revealing the usefulness of this reporter for rapid dose and schedule optimization in the drug development process. © 2007 Nature Publishing Group. |
| Keywords: | signal transduction; protein kinase b; controlled study; unclassified drug; human cell; erlotinib; nonhuman; glioma; mouse; animals; cell survival; mus; cell division; apoptosis; enzyme inhibition; gene amplification; lung neoplasms; animal experiment; animal model; tumor xenograft; enzyme activity; molecular imaging; cell line, tumor; transfection; protein tyrosine kinase; phosphatidylinositol 3 kinase; kinetics; cell culture; head and neck neoplasms; recombinant proteins; proto-oncogene proteins c-akt; plasmids; genes, reporter; dna primers; rapamycin; bioluminescence; perifosine; 2 morpholino 8 phenylchromone; protein kinase b inhibitor; protein kinase b signaling inhibitor 2 |
| Journal Title: | Nature Medicine |
| Volume: | 13 |
| Issue: | 9 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2007-09-01 |
| Start Page: | 1114 |
| End Page: | 1119 |
| Language: | English |
| DOI: | 10.1038/nm1608 |
| PUBMED: | 17694068 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 42" - "Export Date: 17 November 2011" - "CODEN: NAMEF" - "Source: Scopus" |
