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PET Imaging of ⁸⁶Y-Labeled Anti-Lewis Y Monoclonal Antibodies in a Nude Mouse Model: Comparison Between ⁸⁶Y and ¹¹¹In Radiolabels

Nuclear Medicine Service, Departments of Radiology and Medical Physics, Memorial Sloan-Kettering Cancer Center, New York; Ludwig Institute for Cancer Research, New York, New York; Ludwig Institute for Cancer Research, Austin and Repatriation Medical Center, Heidelberg, Victoria, Australia; and Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland

Absorbed doses in ⁹⁰Y radioimmunotherapy are usually estimated by extrapolating from ¹¹¹In imaging data. PET using ⁸⁶Y (ß⁺ 33%; half-life, 14.7 h) as a surrogate radiolabel could be a more accurate alternative. The aim of this study was to evaluate an ⁸⁶Y-labeled monoclonal antibody (mAb) as a PET imaging agent and to compare the biodistribution of ⁸⁶Y- and ¹¹¹In-labeled mAb. Methods: The humanized anti-Lewis Y mAb hu3S193 was labeled with ¹¹¹In or ⁸⁶Y through CHX-A''-diethylenetriaminepentaacetic acid chelation. In vitro cell binding and cellular retention of radiolabeled hu3S193 were evaluated using HCT-15 colon carcinoma cells, a cell line expressing Lewis Y. Nude mice bearing HCT-15 xenografts were injected with ⁸⁶Y-hu3S193 or ¹¹¹In-hu3S193. The biodistribution was studied by measurements of dissected tissues as well as by PET and planar imaging. Results: The overall radiochemical yield in hu3S193 labeling and purification was 42% ± 2% (n = 2) and 76% ± 3% (n = 6) for ⁸⁶Y and ¹¹¹In, respectively. Both radioimmunoconjugates specifically bound to HCT-15 cells. When cellular retention of hu3S193 was studied using ¹¹¹In-hu3S193, 80% of initially cell-bound ¹¹¹In activity was released into the medium as high-molecular-weight compounds within 8 h. When coadministered, in vivo tumor uptake of ⁸⁶Y-hu3S193 and ¹¹¹In-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 imaging, respectively. Conclusion: At 2 d after injection of ¹¹¹In-hu3S193 and ⁸⁶Y-hu3S193 radioimmunoconjugates, the uptake of ¹¹¹In and ⁸⁶Y activity was generally similar in most tissues. After 4 d, however, the concentration of ⁸⁶Y activity was significantly higher in several tissues, including tumor and bone tissue. Accordingly, the quantitative information offered by PET, combined with the presumably identical biodistribution of ⁸⁶Y and ⁹⁰Y radiolabels, should enable more accurate absorbed dose estimates in ⁹⁰Y radioimmunotherapy.

Key Words: ⁸⁶Y • PET imaging • radioimmunotherapy • Lewis Y • 3S193 antibody

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