Positron emission tomography imaging of tumors expressing the human chemokine receptor CXCR4 in mice with the use of 64Cu-AMD3100.

ABSTRACT: PURPOSE:Expression of CXCR4 in cancers has been correlated with poor prognosis and increased metastasis. Quantifying CXCR4 expression non-invasively might aid in prognostication and monitoring therapy. We evaluated a radiolabeled antagonist of CXCR4, ??Cu-AMD3100, as a positron-emitting imaging agent. PROCEDURES:CXCR4-transfected or non-transfected cell lines were injected into mice to form xenografts. Accumulation of ??Cu-AMD3100 in tumors was analyzed by small-animal PET and biodistribution assays. RESULTS:??Cu-AMD3100 accumulated in CXCR4-expressing, but not CXCR4-negative, tumors. For CXCR4-expressing tumors, tumor-to-blood and tumor-to-muscle ratios were 23-41 and 50-59, respectively, depending on tumor type. Excess of unlabeled Cu-AMD3100 or AMD3100 significantly reduced ??Cu-AMD3100 accumulation in CXCR4-expressing tumors. Human-absorbed dose calculations predicted a dose limit of 444 MBq. CONCLUSIONS:CXCR4 can be imaged in tumors using ??Cu-AMD3100. Dosimetry studies suggest that imaging in humans is feasible. We conclude that ??Cu-AMD3100 should be investigated as a potential agent for imaging and quantifying CXCR4 in tumors.

SUBMITTER: Weiss ID 

PROVIDER: S-EPMC5264522 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature