ganglioside--gd2 and Carcinoma

ganglioside--gd2 has been researched along with Carcinoma* in 1 studies

Other Studies

1 other study(ies) available for ganglioside--gd2 and Carcinoma

Article	Year
Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of alpha-emitting atomic nanogenerators targeting disialo-ganglioside GD2. Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Oct-15, Volume: 10, Issue:20 Labeling of specific antibodies with bifunctional chelated Actinium-225 ((225)Ac; an alpha generator) allows the formation of new, highly potent and selective alpha-emitting anticancer drugs. We synthesized and evaluated a radioimmunoconjugate based on 3F8, an IgG(3) antibody that specifically binds to ganglioside GD2, which is overexpressed by many neuroectodermal tumors including neuroblastoma. The (225)Ac-1,4,7,10-tetra-azacylododecane (DOTA)-3F8 construct was evaluated for radiochemical purity and sterility, immunoreactivity, cytotoxicity in vitro, induction of apoptosis on GD2-positive cells, as well as for pharmacological biodistribution and metabolism of the (225)Ac generator and its daughters in a nude mouse xenograft model of neuroblastoma. The (225)Ac-3F8 showed an IC(50) of 3 Bq/ml (80 pCi/ml) on the neuroblastoma cell line, NMB7, in vitro. Apoptosis of these cells was not observed. Biodistribution in mice showed specific targeting of a subcutaneous tumor; there was redistribution of the (225)Ac daughter nuclides mainly from blood to kidneys and to small intestine. Toxicity was examined in cynomolgus monkeys. Monkeys injected with 1 to 3 doses of intrathecal (225)Ac-3F8 radioimmunoconjugate (80 to 150 kBq/kg total dose) did not show signs of toxicity based on blood chemistry, complete blood counts, or by clinical evaluations. Therapeutic efficacy of intrathecal (225)Ac-3F8 was studied in a nude rat xenograft model of meningeal carcinomatosis. The (225)Ac-3F8 treatment improved survival 2-fold from 16 to 34 days (P = 0.01). In conclusion, in vivo alpha generators targeted by 3F8 warrant additional study as a possible new approach to the treatment of carcinomatous meningitis. Topics: Actinium; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Carcinoma; Gangliosides; Haplorhini; Humans; Immunoconjugates; Immunoglobulin G; Injections, Spinal; Meningeal Neoplasms; Mice; Neuroblastoma; Rats; Rats, Nude; Survival Analysis; Tissue Distribution; Transplantation, Heterologous	2004

Article

Year

Treatment of neuroblastoma meningeal carcinomatosis with intrathecal application of alpha-emitting atomic nanogenerators targeting disialo-ganglioside GD2.

Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Oct-15, Volume: 10, Issue:20

Labeling of specific antibodies with bifunctional chelated Actinium-225 ((225)Ac; an alpha generator) allows the formation of new, highly potent and selective alpha-emitting anticancer drugs. We synthesized and evaluated a radioimmunoconjugate based on 3F8, an IgG(3) antibody that specifically binds to ganglioside GD2, which is overexpressed by many neuroectodermal tumors including neuroblastoma. The (225)Ac-1,4,7,10-tetra-azacylododecane (DOTA)-3F8 construct was evaluated for radiochemical purity and sterility, immunoreactivity, cytotoxicity in vitro, induction of apoptosis on GD2-positive cells, as well as for pharmacological biodistribution and metabolism of the (225)Ac generator and its daughters in a nude mouse xenograft model of neuroblastoma. The (225)Ac-3F8 showed an IC(50) of 3 Bq/ml (80 pCi/ml) on the neuroblastoma cell line, NMB7, in vitro. Apoptosis of these cells was not observed. Biodistribution in mice showed specific targeting of a subcutaneous tumor; there was redistribution of the (225)Ac daughter nuclides mainly from blood to kidneys and to small intestine. Toxicity was examined in cynomolgus monkeys. Monkeys injected with 1 to 3 doses of intrathecal (225)Ac-3F8 radioimmunoconjugate (80 to 150 kBq/kg total dose) did not show signs of toxicity based on blood chemistry, complete blood counts, or by clinical evaluations. Therapeutic efficacy of intrathecal (225)Ac-3F8 was studied in a nude rat xenograft model of meningeal carcinomatosis. The (225)Ac-3F8 treatment improved survival 2-fold from 16 to 34 days (P = 0.01). In conclusion, in vivo alpha generators targeted by 3F8 warrant additional study as a possible new approach to the treatment of carcinomatous meningitis.

Topics: Actinium; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Carcinoma; Gangliosides; Haplorhini; Humans; Immunoconjugates; Immunoglobulin G; Injections, Spinal; Meningeal Neoplasms; Mice; Neuroblastoma; Rats; Rats, Nude; Survival Analysis; Tissue Distribution; Transplantation, Heterologous

2004