Dynamic gamma camera studies of In-111-bleomycin complex in normal and glioma bearing rats after in vivo electropermeabilization using exponential high-voltage pulses

This study reports a non-invasive technique to continuously study the uptak e and retention of radiopharmaceuticals after in vivo electropermeabilizati on in tumour bearing rats. A gamma camera was used for a dynamic visualisat ion of In-111-labelled bleomycin in tumour and normal tissue in rats treate d with electrochemotherapy (ECT). The advantages of a continuous in vivo mo nitoring of radiolabelled drugs are the possibilities to give a non-invasiv e, relative quantification of the electropermeabilization effect and to opt imise parameters influencing the electropermeabilization treatment efficien cy. Fischer-344 rats with N32 glioma tumours implanted subcutaneously on th e thigh were used. In-111-bleomycin complex (In-111-BLMC) was given intrave nously as a bolus injection and internalised by local electropermeabilizati on. ECT using exponential pulses was performed on the 4th and the 7th min a fter drug administration using external rectangular electrodes covering the tumour on the leg. From a series of whole-body gamma camera measurements, the drug uptake and clearance of the tumour and selected regions of the bod y were followed over a period up to 10 days. The gamma camera study showed that among the tumour bearing animals, the group treated with In-111-BLMC f ollowed by electropermeabilization resulted in a very high drug retention i n the tumour area and a six to 10 fold increase in tumour uptake compared t o those given In-111-BLMC only. The in vivo stability of the In-111-BLMC wa s also proven when compared with gamma camera studies of (InCl3)-In-111. (C ) 1998 Elsevier Science S.A. All rights reserved.