Uptake and therapeutic effectiveness of /sup 125/I- and /sup 211/At-methylene blue for pigmented melanoma in an animal model system

Journal Article · Tue Aug 01 04:00:00 EDT 1989 · Cancer Res.; (United States)

OSTI ID:5597507

Link, E M; Brown, I; Carpenter, R N; Mitchell, J S

The investigations concerning a targeted radiotherapy for pigmented melanoma with a radiolabeled phenothiazine derivative, 3,7-(dimethylamino)phenazathionium chloride (methylene blue (MTB)), were continued using melanotic and amelanotic sublines of B16 melanoma. Two radionuclides, 125I and 211At, emitting Auger electrons and alpha particles, respectively, replaced 35S previously studied since their biological effectiveness is significantly higher. In vitro autoradiography revealed a selective accumulation of methylene blue labeled with either of the radioisotopes in pigmented melanoma cells but its absence in nonpigmented cells. Treatments with (125I)MTB and (211At)MTB were performed both in vitro and in vivo, with their effectiveness determined by lung clonogenic assay. (125I)MTB proved to be relatively ineffective when incorporated into melanosomes distributed in the cytoplasm, i.e., too far away from the genome. Conspicuous therapeutic effects were achieved with (211At)MTB for pigmented melanoma only. 211At itself did not affect either of the investigated sublines of B16 melanoma confirming once again the high affinity of methylene blue to melanin. Calculations of cumulative radiation doses from (211At)MTB deposited in melanotic melanoma tumors and pigmented normal organs which would be at a particular risk led to the conclusion that (211At)MTB could be used for a highly selective and very efficient targeted radiotherapy of pigmented melanomas without damaging normal tissues.

• Research Organization: Univ. College and Middlesex School of Medicine, London (England)
• OSTI ID: 5597507
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 49:15; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ALPHA DECAY RADIOISOTOPES
AMINES
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIMICROBIAL AGENTS
ASTATINE 211
ASTATINE ISOTOPES
AUTORADIOGRAPHY
AZINES
BETA DECAY RADIOISOTOPES
CHLORIDES
CHLORINE COMPOUNDS
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EXPERIMENTAL NEOPLASMS
HALIDES
HALOGEN COMPOUNDS
HEAVY NUCLEI
HETEROCYCLIC COMPOUNDS
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
MAMMALS
MEDICINE
MELANOMAS
METHYLENE BLUE
MICE
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHENOTHIAZINES
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RBE
RODENTS
THERAPY
TISSUE DISTRIBUTION
TUMOR CELLS
UPTAKE
VERTEBRATES