Production and characterization of Re-188-C595 antibody for radioimmunotherapy of transitional cell bladder cancer

Bladder cancer was responsible for >12,000 deaths in the United States in 1 999, The high-molecular-weight glycoprotein MUC1 mucin is overexpressed on bladder tumors and represents a useful target for radioimmunoscintigraphy a nd radioimmunotherapy. We report on the production and initial tracer studi es of a Re-188-antibody complex directed against this target and intended f or intravesical radioimmunotherapy of superficial bladder cancer. Methods: Re-188 perrhenate was eluted from a W-188/Re-188 generator. C595 antibody w as reduced with 2-mercaptoethanol and was labeled in the presence of stanno us tartrate. The final reaction mixture contained high-molecular-weight con tamination, which was removed from the complex using an affinity separation technique. The specificity and integrity of the antibody complex were test ed by radioimmunoassay and size exclusion chromatography. Tumor localizatio n was investigated using an ex vivo model in human cystectomy specimens. Tr acer amounts of the complex were also administered intravesically to three patients with bladder cancer, who were then imaged by gamma scintigraphy. R esults: The complex was immunoreactive (70% +/- 17%) and specific for MUC1 antigens, A peak corresponding to a protein of 150 kDa was observed on size exclusion chromatography, showing that the complex was homogeneous. Bindin g to bladder tumors was observed in an ex vivo model in which tumors were s uccessfully imaged in four specimens. The mean tumor-to-normal tissue ratio in ex vivo bladders was 7:1. Tumor uptake after intravesical administratio n was confirmed in three patients with bladder cancer (mean tumor-to-normal tissue ratio, 4:1). Conclusion: The C595 antibody was labeled with Re-188, providing a radioimmunoconjugate with high immunoreactivity and specificit y. Its ability to localize in tumors both in an ex vivo model and after int ravesical administration to patients has been shown. This approach will now be extended for the therapy of superficial bladder cancer.