Target specificity of 188Re-labeled B27.1 monoclonal antibodies to ovarian cancer cells in vivo.
BACKGROUND
Currently we are exploring a new multistep pretargeting approach involving administration of a bispecific antibody (B27.1 x P54) which has an anti-CA-125 (B27.1) and antibiotin (P54) paratope. It is followed by the administration of radiolabeled biotinylated liposomes to target the 188Re to the ovarian cancer cells. As a preliminary step to realize this goal, we determined the target specificity of the monoclonal antibodies (B27.1) to the ovarian cancer cells in vivo.


METHODS
B27.1 monoclonal antibodies were photoreduced using UV light and incubated with reduced 188Re for 30 min at 25degreesC. 188Re-labeled B27.1 antibodies were purified using size exclusion chromatography. A comparative biodistribution of Re-B27.1 and 188Re was performed in nude mice xenografted with NIH:OVCAR-3 cells.


RESULTS
While free rhenium distributed preferentially into thyroid and stomach with insignificant accumulation in the cancer cells, about 20% of the injected dose of 188Re-B27.1 was recovered in ascites cells with insignificant localization in other organs four hours after administration.


CONCLUSIONS
The study validates the affinity of the B27.1 antibodies to the ovarian cancer cells in vivo.
Palakurthi
Srinath
S
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. Srinath.palakurthi@sdstate.edu
Wilson
John
J
McQuarrie
Steve A
SA
Suresh
Mavanur R
MR
Mercer
John R
JR
Miller
Gerald G
GG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000276:immunology*; D011868:Radioisotopes; D012211:Rhenium; D012680:Sensitivity and Specificity; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium