TARGETING DISSEMINATED MELANOMA WITH RADIOLABELED METHYLENE-BLUE - COMPARATIVE BIO-DISTRIBUTION STUDIES IN MAN AND ANIMALS

Targeted radiotherapy for pigmented melanoma with 3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with Astatine -211 (At-211; alpha-particle emitter) proved to be very effective in a nimal model systems. Since the results justified an introduction of th e treatment to the clinic, the aim of the bio-distribution studies usi ng [I-123]-MTB and [I-131]-MTB in patients was to confirm selectivenes s of radiolabelled MTB uptake in melanoma lesions. The investigations were carried out using planar and SPECT (single photon emission comput ed tomography) gamma-cameras. A stable uptake of radioiodinated MTB wa s found in pigmented melanomas in man, with tumour/surrounding tissue and tumour/blood ratios amounting to 9 at 19 h after a single i.v. inj ection. A time-dependent kinetics of radioiodinated MTB distribution w as similar to that observed in human melanoma-bearing athymic mice. Bl ood radioactivity decreased by about 90% during the first 2.5 min afte r i.v. injection of the compound (T-1/2 biol = 0.58 min). Its retentio n time in various organs was either the same or very similar to that c haracteristic of the blood. A rapid uptake of radioiodinated MTB in th e liver and kidneys confirmed the importance of these organs in excret ing the compound: 25-30% of the radioactivity administered was expelle d with urine over the first 24 h after the injection. There was no obv ious retention of radioiodinated MTB in the brain over the observation period and in the eyes for at least the first 14 h.