title: Intralesional targeted alpha therapy for metastatic melanoma.
abstract: This paper reports the development and application of intralesional targeted alpha therapy (TAT) for melanoma, being the first part of a program to establish a new systemic therapy.
  
  
  BACKGROUND
  Labelling the benign targeting vector 9.2.27 with 213Bi forms the alpha-immunoconjugate (AIC), which is highly cytotoxic to targeted melanoma cells.
  
  
  OBJECTIVE
  To investigate the safety and efficacy of intralesional AIC in patients with metastatic skin melanoma.
  
  
  RESULTS
  16 melanoma patients were recruited. All the patients were positive to the monoclonal antibody 9.2.27. AIC doses from 50 to 450 mCi injected into lesions of different sizes resulted in massive cell death, as observed by the presence of tumour debris. The AIC was very effective in delivering a high dose to the tumour while sparing other tissues. There were no significant changes in blood proteins and electrolytes. There was no evidence of a human-antimouse-antibody reaction. Evidence of significant decline in serum marker melanoma-inhibitory-activity protein (MIA) at 2 weeks post-TAT was observed.
  
  
  CONCLUSIONS
  Intralesional TAT for melanoma was found to be quite safe up to 450 mCi, and efficacious at a dose of 200 mCi. MIA, apoptosis and ki67 proliferation marker tests all indicated that TAT is a promising therapy for the control of inoperable secondary melanoma or primary ocular melanoma.
authors.affiliation: Centre For Experimental Radiation Oncology, St. George Hospital, Kogarah, NSW 2217, Australia. b.allen@unsw.edu.au
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Allen
authors.forename: Chand
authors.initials: C
authors.lastname: Raja
authors.forename: Syed
authors.initials: S
authors.lastname: Rizvi
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Wendy
authors.initials: W
authors.lastname: Tsui
authors.forename: Peter
authors.initials: P
authors.lastname: Graham
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Reisfeld
authors.forename: John
authors.initials: J
authors.lastname: Kearsley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000512:Alpha Particles / Q000009:adverse effects / Q000627:therapeutic use*; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000097:blood; D001729:Bismuth / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006207:Half-Life; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015552:Injections, Intralesional; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D014018:Tissue Distribution
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018796:Immunoconjugates; D001729:Bismuth