Effects of dextranation on the pharmacokinetics of short peptides. A PET study on mEGF

The effects of dextranation on the biodistribution of mouse epidermal growt h factor (mEGF, 6 kDa) were assessed. By reductive amination, mEGF was coup led to 13 and 46 kDa dextran. The two dextranated conjugates and free mEGF were labeled with the positron-emitting nuclide Br-76 (T-1/2 = 16 h). After intravenous administration to Sprague Dawley rats, the radioactivity biodi stribution was evaluated by positron emission tomography (PET) and by measu rements of dissected tissues. The dextranation prolonged the retention time in blood, especially when the dextran chain was long. [Br-76]-mEGF-dextran conjugates were shown to have significantly, more than 5 times, lower kidn ey accumulation than the nonconjugated [Br-76]mEGF. In conclusion, dextrana tion affects the biodistribution of mEGF in vivo giving a prolonged circula tion time, a decreased uptake in kidney, and an increased spleen accumulati on.