期刊
CANCER RESEARCH
卷 69, 期 10, 页码 4510-4516出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-08-3781
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类别
资金
- NIH [R24 CA83060, P30 CA91842, R01 GM073857, R01 133890, R21 CA125280, R32 CA110422-03]
- Department of Defense [PC040435, PC050351, BC061356]
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 alpha-helix when the extracellular pH (pH(e)) 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 Cu-64 conjugated to the pHLIP (Cu-64-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(e) of PC-3 and LNCaP tumors measured in magnetic resonance spectroscopy experiments by the P-31 chemical shift of the pH(e) 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. [Cancer Res 2009:69(10):45 10-6]
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