A novel technology for the imaging of acidic prostate tumors by positron emission tomography Journal Article
| Authors: | Vavere, A. L.; Biddlecombe, G. B.; Spees, W. M.; Garbow, J. R.; Wijesinghe, D.; Andreev, O. A.; Engelman, D. M.; Reshetnyak, Y. K.; Lewis, J. S. |
| Article Title: | A novel technology for the imaging of acidic prostate tumors by positron emission tomography |
| Abstract: | Solid tumors often develop an acidic environment due to the Warburg effect. The effectiveness of diagnosis and therapy may therefore be enhanced by the design and use of pH-sensitive agents that target acidic tumors. Recently, a novel technology was introduced to target acidic tumors using pH low insertion peptide (pHLIP), a peptide that inserts across cell membranes as an α-helix when the extracellular pH (pH<sub>e</sub>) is acidic. In this study, we expanded the application of the pHLIP technology to include positron emission tomography imaging of the acidic environment in prostate tumors using <sup>64</sup>Cu conjugated to the pHLIP (<sup>64</sup>Cu-DOTA-pHLIP). Studies showed that this construct avidly accumulated in LNCaP and PC-3 tumors, with higher uptake and retention in the LNCaP tumors. Uptake correlated with differences in the bulk pH<sub>e</sub> of PC-3 and LNCaP tumors measured in magnetic resonance spectroscopy experiments by the <sup>31</sup>P chemical shift of the pH<sub>e</sub> marker 3-aminopropylphosphonate. This article introduces a novel class of noninvasive pH-selective positron emission tomography imaging agents and opens new research directions in the diagnosis of acidic solid tumors. ©2009 American Association for Cancer Research. |
| Keywords: | controlled study; carrier protein; unclassified drug; human cell; nonhuman; positron emission tomography; animal cell; mouse; animals; mice; animal experiment; animal model; membrane proteins; ph; prostatic neoplasms; models, animal; amino acid sequence; molecular sequence data; drug distribution; mice, nude; prostate tumor; positron-emission tomography; radiopharmaceutical agent; nuclear magnetic resonance spectroscopy; chromatography, high pressure liquid; copper 64; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; hydrogen-ion concentration; proton nuclear magnetic resonance; cell strain lncap; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid ph low insertion peptide cu 64; ph low insertion peptide; phosphonic acid derivative; acidity; copper radioisotopes; maleimides |
| Journal Title: | Cancer Research |
| Volume: | 69 |
| Issue: | 10 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2009-05-15 |
| Start Page: | 4510 |
| End Page: | 4516 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-08-3781 |
| PUBMED: | 19417132 |
| PROVIDER: | scopus |
| PMCID: | PMC2690701 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 30 November 2010" - "CODEN: CNREA" - "Source: Scopus" |
