Preclinical targeted alpha therapy for subcutaneous melanoma.
An alpha-emitting immunoconjugate (AIC) against malignant melanoma was prepared from the radioisotope bismuth-213 and a melanoma monoclonal antibody, and was used to control the growth of subcutaneous melanoma in a nude mouse model. Activity tolerances were found to be 8 mCi/kg for intraperitoneal injection of the conjugate, and 10 mCi/kg for intralesional injections. Local targeted alpha therapy (TAT) via intralesional injections of activities in the range 12.5-200 microCi shows a very high level of inhibition of tumorigenesis and regression of tumours. Results show that isolated cancer cells and preangiogenic cell clusters can be eliminated by local TAT, and that intralesional injections of 100 microCi of AIC are sufficient to cause complete regression of melanomas with volumes up to 300 mm3 without any observed side effects. Systemic TAT was less effective, with all tumours experiencing growth delay and limited inhibition of tumour growth. These data provide the basis for clinical trials of TAT in recurrent subcutaneous melanoma.
Allen
B J
BJ
Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St Kogarah, Australia. b.allen@unsw.edu.au
Rizvi
S M
SM
Tian
Z
Z
D000818:Animals; D001729:Bismuth / Q000627:therapeutic use*; D001835:Body Weight / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008545:Melanoma / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011868:Radioisotopes / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000532:radiotherapy*; D013997:Time Factors; D014018:Tissue Distribution
D011868:Radioisotopes; D001729:Bismuth