Localization of radiolabeled anti-CEA antibody in subcutaneous and intrahepatic colorectal xenografts: influence of tumor size and location within host organ on antibody uptake.
BACKGROUND
Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors.


METHODS
Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([(125)I]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy study, mice bearing intrahepatic metastatic tumors were injected with [(131)I]A5B7.


RESULTS
Subcutaneous tumors and large metastatic deposits had similar uptake (e.g., approximately 15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., approximately 80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6+/-12.9 vs. treated mean survival of 39.1+/-30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly supporting the use of in vivo imaging in metastatic tumor therapy studies.


CONCLUSIONS
Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits.
Dearling
Jason L J
JL
Cancer Research UK Targeting and Imaging Group, Research Department of Oncology, UCL Cancer Institute, Paul O'Gorman Building, University College London, London, UK. j.dearling@hotmail.com
Flynn
Aiden A
AA
Qureshi
Uzma
U
Whiting
Stephen
S
Boxer
Geoffrey M
GM
Green
Alan
A
Begent
Richard H J
RH
Pedley
R Barbara
RB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000556:secondary*; D008657:Metabolic Clearance Rate; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
C518613:A5B7 monoclonal antibody; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D019275:Radiopharmaceuticals