RT Journal Article
SR Electronic
T1 PET Imaging of <sup>86</sup>Y-Labeled Anti-Lewis Y Monoclonal Antibodies in a Nude Mouse Model: Comparison Between <sup>86</sup>Y and <sup>111</sup>In Radiolabels
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1281
OP 1287
VO 42
IS 8
A1 Anna Lövqvist
A1 John L. Humm
A1 Arif Sheikh
A1 Ron D. Finn
A1 Jacek Koziorowski
A1 Shutian Ruan
A1 Keith S. Pentlow
A1 Achim Jungbluth
A1 Sydney Welt
A1 Fook T. Lee
A1 Martin W. Brechbiel
A1 Steven M. Larson
YR 2001
UL http://jnm.snmjournals.org/content/42/8/1281.abstract
AB 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.