A protocol was developed to study the drug uptake from in vivo electroperme
abilization at different settings of parameters influencing the uptake effi
ciency. Radiolabelled diethylenetriaminepentaacetic acid (DTPA) was used to
trace the distribution and internalization of a hydrophilic drug after in
vivo electropermeabilization. Skeletal muscle tissue in rat was treated wit
h permeabilizing: electric pulses before or after intravenous administratio
n of Tc-99m-DTPA. The drug accumulation in the treated volume was subsequen
tly evaluated with a scintillation camera. The dependence of uptake on fiel
d strength and duration of the applied electric pulses was investigated for
exponentially decaying pulses and square wave pulses. Further, the uptake
dependence on time interval between injection and pulsation was studied as
well as the uptake dependence on the number of pulses applied in a single e
lectropermeabilization treatment. Dynamic gamma camera studies were perform
ed to quantify the time scale of the drug uptake in electropermeabilized ti
ssue. (C) 1999 Elsevier Science B.V. All rights reserved.