In vivo studies of pharmacokinetics and efficacy of Bismuth-213 labeled antimelanoma monoclonal antibody 9.2.27.
OBJECTIVE
Key objectives of the study were to determine the pharmacokinetics and efficacy of the alpha emitting Bismuth-213 labeled 9.2.27 alpha-immunoconjugate (AIC).


METHODS
Balb/c nude mice were injected with varying doses of AIC to determine the pharmacokinetics of the AIC. The results were normalized to percent counts per minute (CPM) per gram per 3.7 MBq of the AIC (%CPM/g/3.7MBq) for each organ. Efficacy was determined by injected varying doses of AIC to different stages of tumor growth for intra-lesional, systemic and multiple dose TAT.


RESULTS
Biodistribution studies showed similar pharmacokinetics for blood and brain, liver, kidneys, spleen, gut, heart, lungs and bone marrow, indicating that there was no retention of AIC. This is particularly important for brain (due to the presence of NG2+ cells) as the antibody 9.2.27 may reach NG2 positive cells. Tumor growth at 2-days post-inoculation was completely inhibited by TAT. The response to TAT was inversely proportional to tumor growth, i.e., a reduction in response was observed with increased tumor burden. A multiple dose regime was found to be more effective than single dose.


CONCLUSIONS
TAT is effective for the treatment of micrometastatic melanoma, when the tumor is preangiogenic in the form of isolated cells or cell clusters. There is no evidence of retention of AIC in brain, kidneys and other vital organs.
Rizvi
Syed M Abbas
SM
Center for Experimental Radiation Oncology, Cancer Care Center, St. George Hospital, Kogarah, Sydney, NSW, Australia. rizvis@sesahs.nsw.gov.au
Qu
Chang Fa
CF
Song
Yan Jun
YJ
Raja
Chand
C
Allen
Barry J
BJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000941:Antigens / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001729:Bismuth / Q000493:pharmacokinetics*; D006207:Half-Life; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011509:Proteoglycans / Q000276:immunology*; D011868:Radioisotopes; D014018:Tissue Distribution; D000099216:Chondroitin Sulfate Proteoglycan 4
D000911:Antibodies, Monoclonal; D000941:Antigens; D000951:Antigens, Neoplasm; D001729:Bismuth; D011509:Proteoglycans; D011868:Radioisotopes; D000099216:Chondroitin Sulfate Proteoglycan 4