TY - JOUR
T1 - In vitro and in vivo characterization of 177Lu-huA33. A radioimmunoconjugate against colorectal cancer
AU - Almqvist, Ylva
AU - Steffen, Ann Charlott
AU - Tolmachev, Vladimir
AU - Divgi, Chaitanya R.
AU - Sundin, Anders
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/11
Y1 - 2006/11
N2 - Introduction: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of 177Lu-labeled huA33. Methods: huA33 was labeled with the β-emitting therapeutic nuclide 177Lu using the chelator CHX-A″-DTPA, and the properties of the 177Lu-CHX-A″-huA33 (177Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. Results: The 177Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a KD value of 2.3±0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of 177Lu-huA33 was very high, peaking at 134±21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70±30, 10 days pi. Throughout the study, the uptake of 177Lu in bone (known to accumulate free 177Lu) was low, and the fraction of protein-bound 177Lu in plasma samples was high (95% to 99%). This indicates high stability of the 177Lu-huA33 conjugate in vivo. Conclusion: The 177Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.
AB - Introduction: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of 177Lu-labeled huA33. Methods: huA33 was labeled with the β-emitting therapeutic nuclide 177Lu using the chelator CHX-A″-DTPA, and the properties of the 177Lu-CHX-A″-huA33 (177Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. Results: The 177Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a KD value of 2.3±0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of 177Lu-huA33 was very high, peaking at 134±21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70±30, 10 days pi. Throughout the study, the uptake of 177Lu in bone (known to accumulate free 177Lu) was low, and the fraction of protein-bound 177Lu in plasma samples was high (95% to 99%). This indicates high stability of the 177Lu-huA33 conjugate in vivo. Conclusion: The 177Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.
KW - Lu
KW - A33 antigen
KW - Antibody
KW - Colorectal cancer
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U2 - 10.1016/j.nucmedbio.2006.09.003
DO - 10.1016/j.nucmedbio.2006.09.003
M3 - Article
C2 - 17127172
AN - SCOPUS:33751233510
VL - 33
SP - 991
EP - 998
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
SN - 0969-8051
IS - 8
ER -