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, ⁶⁴Cu-AMD3100, as a positron-emitting imaging agent. PROCEDURES: CXCR4-transfected or non-transfected cell lines were injected into mice to form xenografts. Accumulation of ⁶⁴Cu-AMD3100 in tumors was analyzed by small-animal PET and biodistribution assays. RESULTS: ⁶⁴Cu-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 ⁶⁴Cu-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 ⁶⁴Cu-AMD3100. Dosimetry studies suggest that imaging in humans is feasible. We conclude that ⁶⁴Cu-AMD3100 should be investigated as a potential agent for imaging and quantifying CXCR4 in tumors.
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, ⁶⁴Cu-AMD3100, as a positron-emitting imaging agent. PROCEDURES: CXCR4-transfected or non-transfected cell lines were injected into mice to form xenografts. Accumulation of ⁶⁴Cu-AMD3100 in tumors was analyzed by small-animal PET and biodistribution assays. RESULTS: ⁶⁴Cu-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 ⁶⁴Cu-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 ⁶⁴Cu-AMD3100. Dosimetry studies suggest that imaging in humans is feasible. We conclude that ⁶⁴Cu-AMD3100 should be investigated as a potential agent for imaging and quantifying CXCR4 in tumors.
Authors: Orit Jacobson; Ido D Weiss; Lawrence Szajek; Joshua M Farber; Dale O Kiesewetter Journal: Bioorg Med Chem Date: 2009-01-15 Impact factor: 3.641
Authors: Orit Jacobson; Ido D Weiss; Lawrence P Szajek; Gang Niu; Ying Ma; Dale O Kiesewetter; Amnon Peled; Henry S Eden; Joshua M Farber; Xiaoyuan Chen Journal: J Control Release Date: 2011-09-22 Impact factor: 9.776
Authors: Ole Tietz; Nazila Kamaly; Graham Smith; Elham Shamsaei; Kishore K Bhakoo; Nicholas J Long; Eric O Aboagye Journal: Am J Nucl Med Mol Imaging Date: 2013-07-10