PET imaging of Y-86-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: Comparison between Y-86 and In-111 radiolabels

Absorbed doses in Y-90 radioimmunotherapy are usually estimated by extrapol ating from In-111 imaging data. PET using Y-86 (beta (+) 33%; half-life, 14 .7 h) as a surrogate radiolabel could be a more accurate alternative. The a im of this study was to evaluate an Y-86-labeled monoclonal antibody (mAb) as a PET imaging agent and to compare the biodistribution of Y-86- and In-1 11-labeled mAb. Methods The humanized anti-Lewis Y mAb hu3S193 was labeled with In-111 or 86Y through CHX-A"-diethylenetriaminepentaacetic acid chelat ion. In vitro cell binding and cellular retention of radiolabeled hu3S193 w ere evaluated using HCT-15 colon carcinoma cells, a cell line expressing Le wis Y. Nude mice bearing HCT-15 xenografts were injected with Y-86-hu3S193 or In-111-hu3S193. The biodistribution was studied by measurements of disse cted tissues as well as by PET and planar imaging. Results: The overall rad iochemical yield in hu3S193 labeling and purification was 42 +/-2% (n = 2) and 76%+/-3% (n = 6) for Y-86 and In-111, respectively. Both radioimmunocon jugates specifically bound to HCT-15 cells. When cellular retention of hu3S 193 was studied using In-111-hu3S193, 80% of initially cell-bound In-111 ac tivity was released into the medium as high-molecular-weight compounds with in 8 h. When coadministered, in vivo tumor uptake of Y-86-hu3S193 and In-11 1-hu3S193 reached maximum values of 30 +/-6 and 29 +/-6 percentage injected dose per gram and tumor sites were easily identifiable by PET and planar i maging, respectively. Conclusion: At 2 d after injection of In-111-hu3S193 and Y-86-hu3S193 radioimmunoconjugates, the uptake of In-111 and Y-86 activ ity was generally similar in most tissues. After 4 d, however, the concentr ation of Y-86 activity was significantly higher in several tissues, includi ng tumor and bone tissue. Accordingly, the quantitative information offered by PET, combined with the presumably identical biodistribution of Y-86 and Y-90 radiolabels, should enable more accurate absorbed dose estimates in Y -90 radioimmunotherapy.