PET imaging of (86)Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: comparison between (86)Y and (111)In radiolabels.
Absorbed doses in (90)Y radioimmunotherapy are usually estimated by extrapolating from (111)In imaging data. PET using (86)Y (beta(+) 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 (86)Y-labeled monoclonal antibody (mAb) as a PET imaging agent and to compare the biodistribution of (86)Y- and (111)In-labeled mAb.


METHODS
The humanized anti-Lewis Y mAb hu3S193 was labeled with (111)In or (86)Y 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 (86)Y-hu3S193 or (111)In-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 (86)Y and (111)In, respectively. Both radioimmunoconjugates specifically bound to HCT-15 cells. When cellular retention of hu3S193 was studied using (111)In-hu3S193, 80% of initially cell-bound (111)In activity was released into the medium as high-molecular-weight compounds within 8 h. When coadministered, in vivo tumor uptake of (86)Y-hu3S193 and (111)In-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.


CONCLUSIONS
At 2 d after injection of (111)In-hu3S193 and (86)Y-hu3S193 radioimmunoconjugates, the uptake of (111)In and (86)Y activity was generally similar in most tissues. After 4 d, however, the concentration of (86)Y 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 (86)Y and (90)Y radiolabels, should enable more accurate absorbed dose estimates in (90)Y radioimmunotherapy.
Lövqvist
A
A
Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Humm
J L
JL
Sheikh
A
A
Finn
R D
RD
Koziorowski
J
J
Ruan
S
S
Pentlow
K S
KS
Jungbluth
A
A
Welt
S
S
Lee
F T
FT
Brechbiel
M W
MW
Larson
S M
SM
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000378:metabolism; D001345:Autoradiography; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015021:Yttrium Radioisotopes
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes