Bismuth-213 radioimmunotherapy with C595 anti-MUC1 monoclonal antibody in an ovarian cancer ascites model.
OBJECTIVE
Control of ovarian cancer (OC) ascites remains a major objective in post-surgical treatment. The aim of this study was to investigate the effect of targeted alpha therapy (TAT) for the control of ascites in an OC ascites mouse model; the biodistribution of (213)Bi-C595 and its long term toxicity.


METHODS
The expression of tumor-associated antigen mucin-1 (MUC-1) in OVCAR3 ascites cells in mice and OC cancer tissues in patients was detected by indirect immmunostaining. The monoclonal antibody (MAb) C595 was labeled with (213)Bi using the chelator cDTPA to form the alpha-immunoconjugate (AIC). Mice were injected with different concentrations of AIC by i.p administration. Changes in tumor progression were assessed by measurement of the circumference of the abdomen.


RESULTS
MUC-1 is strongly expressed in 73% of OC tissues. At 9 days post-cell inoculation in mice, a single injection of 355 MBq/kg of (213)Bi-C595 can prolong survival by 25 days. A high tumor: blood ratio (5.8) was found in biodistribution study. The maximum tolerance dose (MTD) was more than 1180 MBq/kg up to 21 weeks.


CONCLUSIONS
C595 is a specific targeting vector for ovarian cancer cells, which show a high percentage of expression of MUC1. (213)Bi-C595 can effectively target and kill ovarian cancer cells in vitro and in vivo. (213)Bi-C595 is the recommended alpha conjugate for a Phase I clinical trial for ovarian cancer.
Song
Emma Y
EY
Centre for Experimental Radiation Oncology, Cancer Care Centre, St. George Hospital, Kogarah, UK.
Qu
Chang F
CF
Rizvi
Syed M A
SM
Raja
Chand
C
Beretov
Julia
J
Morgenstern
Alfred
A
Apostolidis
Christos
C
Bruchertseifer
Frank
F
Perkins
Alan
A
Allen
Barry J
BJ
D000512:Alpha Particles; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001729:Bismuth / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000032:analysis / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000009:adverse effects; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; C060192:MUC1 protein, human; D018396:Mucin-1; D001729:Bismuth