Tissue distribution of a erythropoietin receptor binding peptide in rats shown by Quantitative Whole-Body Autoradiography (QWBA) and microautoradiography (MARG)

摘要

The tissue distribution of a peptide related to a family having erythropoiesis stimulating activity, binds to erythropoietin receptor (EPOr), but has no sequence homology to the human EPOr, was evaluated in albino rats given a single intravenous (IV) or a subcutaneous (SC) dose of the ~(14)C-Test Peptide at 5mg/kg. Rats were euthanized at 1, 4, 8, 24, 72, 120, 168, 336, and 672 h post-dose (IV), or at 1, 24, and 168 h post-dose (SC). Tissue concentration and localization was demonstrated using QWBA and MARG. Drugderived radioactivity was distributed to tissues of rats through 672 h and 168 h post-IV or SC dose, respectively. The highest concentrations of radioactivity found at 1 h post-dose were in the renal cortex and medulla, liver, blood vessels, spleen, and bone marrow. There was differential distribution between the red and white pulp of the spleen. Similar patterns of tissue distribution were observed following IV and SC administration. analysis of the kidney showed radioactivity localized to the glomeruli and tubules, which suggested a route of elimination of drug-derived radioactivity, and/or binding to renal EPOr. MARG results suggested that radioactivity partitioned into the liver, spleen, lymph nodes and thymus (extramedullary hematopoietic sites). MARG on bone marrow showed a very high localization, which was likely a function of the known high density of EPOr in the bone marrow. These data suggest that the Test peptide, which binds to the EPOr, but has no sequence homology to rHuEPO, localizes selectively to known erythropoietic tissues.