Accumulation of radiolabeled anti-CEA antibody (mT84.66) in the case of multiple LS174T tumors in a nude mouse model.
A comparison was made between labeled antibody accumulations in nude mice having either single or multiple human xenografts. The LS174T tumors were implanted subcutaneously. All animals were given 2 micrograms of labeled murine anti-carcinoembryonic antigen (CEA) monoclonal antibody 111In-mT84.66. Some animals were also given specific antibody pretreatment (SAP) of 200 micrograms of unlabeled mT84.66 to reduce liver accumulation of activity. In order to represent these multiple tumor examples, a simple initial-phase pharmacokinetic model was first fitted to each of the two groups (SAP and PBS treated) of single-tumor animals. Using the resultant six non-adjustable parameters as constants, the n = 1 uptake model was then used to represent tumor, liver and blood accumulations (%injected dose/organ) in the multiple-tumor animals. The model was found to be a good representation; in particular, it had far better agreement than single tumor predictions in the PBS mice. Differences between the single-tumor accumulations and those seen in multiple tumor examples were generally between two- and three-fold. The model also demonstrated that the result of SAP was to essentially eliminate the effect of liver targeting of tumor-secreted CEA. We conclude that an initial-phase one-tumor model can describe the decrease of accumulation of activity in the case of multiple tumors in nude mice in both untreated (PBS) and pretreated conditions. Implications for clinical imaging and therapy with monoclonal agents are discussed.
Williams
L E
LE
Division of Radiology, City of Hope National Medical Center, Duarte, CA 91010, USA. lwilliams@coh.org
Beatty
B G
BG
Shively
J E
JE
Beatty
J D
JD
D000465:Algorithms; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007205:Indium Radioisotopes