Distribution of immunoglobulin Fab fragment conjugated with HIV-1 REV peptide following intravenous administration in rats.

HIV-1 REV peptide (positions 34-50) is well-known as a cell-permeating peptide. In this study, we investigated the distribution of Fab fragment of immunoglobulin conjugated with REV peptide (REV-Fab) following intravenous administration in rats, and compared with those of the native Fab fragment (nFab). Radioiodinated REV-Fab or nFab ((125)I-REV-Fab or (125)I-nFab, respectively) was given in a single intravenous dose of 2 mg/kg (3 MBq/kg). Total radioactive and TCA-insoluble radioactive concentrations in blood, whole-body autoradiography (ARG), and urinary excretion rates were assayed following administration. Regarding blood and plasma, total radioactive and TCA-insoluble radioactive concentrations for (125)I-REV-Fab were remarkably lower than those for (125)I-nFab. In the whole-body ARG at 4 h after administration, (125)I-REV-Fab produced remarkably higher radioactivity in the adrenal gland, spleen, and liver, compared to (125)I-nFab. Regarding urinary excretion rates, approximately 70% of the radioactive dose was excreted in the form of a low-molecular-weight component by 24 h after administration for both samples. (125)I-REV-Fab may penetrate quickly from blood to adrenal gland, spleen, liver, and other tissues after intravenous administration to rats, and then did not stay in situ and was digested and excreted mostly via the renal route by 24 h. With these features, cell-permeating peptides are expected to help the development of new antibody pharmaceuticals.