Uptake of 125I-PDGF-AB to the blood after extravascular administration in mice

The kinetics of exogenously given I-125-platelet-derived growth factor-AB (PDGF-AB) was studied in mice. I-125-PDGF-AB was injected either intraperitoneally, intramuscularly or subcutaneously and the resulting concentrations of I-125-radioactivity monitored in the blood at different times. The serum levels of I-125-radioactivity rose to a maximum 2-4 hours after injection, before decreasing. Precipitation of serum with trichloroacetic acid demonstrated that 50 per cent or more of the I-125 remained in macromolecular form. Further, gel chromatography studies showed that the molecular size of the labelled material in serum, three hours after injection, was the same as that of the original I-125-PDGF-AB. In addition, a low-molecular weight fraction was observed, indicating the presence of degradation products. The largest proportion of degraded material was obtained after subcutaneous administration. The absence of partially degraded I-125-labelled fragments, e.g. I-125 oligopeptides, indicates complete rather than limited degradation and suggests that the I-125-PDGF-AB had been processed by cellular uptake. It is concluded that extra-vascularly given PDGF-AB in mice is taken up into the blood in intact macromolecular form. This finding suggests that it is possible to administer PDGF extravascularly to obtain a prolonged increase in the concentration of intact PDGF in the blood.