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

Journal of Nuclear Medicine

Fook T. Lee¹  John L. Humm¹  Shutian Ruan¹  Jacek Koziorowski¹  Sydney Welt¹  Keith S. Pentlow¹  Anna Lövqvist¹  Martin W. Brechbiel¹  Arif Sheikh¹  Steven M. Larson¹  Ron D. Finn¹  Achim Jungbluth¹ 

[1] 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 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 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

关键词: ⁸⁶Y;    PET imaging;    radioimmunotherapy;    Lewis Y;    3S193 antibody;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Absorbed doses in 90Y radioimmunotherapy are usually estimated by extrapolating from 111In imaging data. PET using 86Y (β+ 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.

【 授权许可】

Unknown