title: Targeting disseminated melanoma with radiolabelled methylene blue: Comparative bio-distribution studies in man and animals.
abstract: Targeted radiotherapy for pigmented melanoma with 3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with Astatine-211 (211At; alpha-particle emitter) proved to be very effective in animal model systems. Since the results justified an introduction of the treatment to the clinic, the aim of the bio-distribution studies using [123I]-MTB and [131I]-MTB in patients was to confirm selectiveness of radiolabelled MTB uptake in melanoma lesions. The investigations were carried out using planar and SPECT (single photon emission computed tomography) gamma-cameras. A stable uptake of radioiodinated MTB was 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. injection. A time-dependent kinetics of radioiodinated MTB distribution was similar to that observed in human melanoma-bearing athymic mice. Blood radioactivity decreased by about 90% during the first 2.5 min after i.v. injection of the compound (T1/2biol = 0.58 min). Its retention time in various organs was either the same or very similar to that characteristic of the blood. A rapid uptake of radioiodinated MTB in the liver and kidneys confirmed the importance of these organs in excreting the compound: 25-30% of the radioactivity administered was expelled with urine over the first 24 h after the injection. There was no obvious retention of radioiodinated MTB in the brain over the observation period and in the eyes for at least the first 14 h.
authors.affiliation: Department of Molecular Pathology, University College London School of Medicine, London.
authors.forename: E M
authors.initials: EM
authors.lastname: Link
authors.forename: D C
authors.initials: DC
authors.lastname: Costa
authors.forename: D
authors.initials: D
authors.lastname: Lui
authors.forename: P J
authors.initials: PJ
authors.lastname: Ell
authors.forename: P J
authors.initials: PJ
authors.lastname: Blower
authors.forename: M F
authors.initials: MF
authors.lastname: Spittle
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001921:Brain / Q000378:metabolism; D004396:Coloring Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005123:Eye / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D008751:Methylene Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: D004396:Coloring Agents; D007457:Iodine Radioisotopes; D008751:Methylene Blue