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lüll Recombinant human erythropoietin coupled to near-infrared fluorescence dye Cy5 5 Chopra AMolecular Imaging and Contrast Agent Database (MICAD)-/-ä 2004[]; ä (ä): äErythropoietin (Epo) is a heavily glycosylated chemokine that is expressed primarily in the adult kidney (during the fetal stage of development, Epo is produced mainly in the liver and not the kidneys), mediates its effects through the erythropoietin receptor (Epo-R), and is known to regulate the process of erythropoiesis (red blood cell formation from hematopoietic cells in the bone marrow) in the hematopoietic system (1). Epo-R is also found in other tissues and is believed to protect cells in the cardiac and neuronal tissues from hypoxic injury and apoptosis. The expression of Epo and Epo-R and the cell signaling pathways involved in bringing about the biological effects of this receptor-ligand complex have been described by Chateauvieux et al. (1). The use of recombinant human Epo (rhuEpo) has been approved by the United States Food and Drug Administration for the treatment of anemia in certain HIV patients and individuals undergoing chemotherapy for non-myeloid cancer or those who are experiencing chronic kidney failure. Meta-analysis of data obtained from clinical trials has shown that the use of rhuEpo in the clinic is associated with increased adverse thrombo-vascular events or neoplastic tumor progression that results in the mortality of individuals with certain types of cancer (2). In a mouse model of breast cancer it has been shown that, when rhuEpo was used in combination with chemotherapy, there was an increased incidence of cancer metastasis in the animals (3). The co-expression of Epo and Epo-R has been observed in certain neoplasms, including non-small cell lung cancer (NSCLC), and a clinical investigation has shown that expression of these genes in the NSCLC tumors correlated with a negative outcome for the patient (4). However, other studies could not establish a clear link between the expression of Epo and Epo-R and the development of cancer because the Epo-R status of a tumor cannot be determined accurately with currently used immunohistochemical methods, due to the lack of antibodies that can specifically and selectively bind to the Epo-R (5). Therefore, the development of alternative probes that specifically target the Epo-R and can be used with noninvasive imaging techniques to detect and quantify the receptor in vivo is necessary (5). Doleschel et al. coupled Cy5.5, a near-infrared dye, to rhuEpo (Epo-Cy5.5) and evaluated the fluorescent conjugate to visualize the expression of EpoR with fluorescence-mediated tomography (FMT) in human lung cancer xenografts in mice (5). The biodistribution of the probe in these animals was also investigated.ä |