Localization by whole-body autoradiography of intact and fragmented radiolabeled antibodies in a metastatic human colonic cancer model.
In this report, we have employed macroautoradiography to compare the tumor targeting of 125I-labeled anti-carcinoembryonic antigen (CEA) MAb (NP-4) to 125I-labeled anti-colon-specific antigen-p (CSAp) MAb (Mu-9) and their labeled F(ab')2 and Fab' fragments, in nude mice each bearing large dorsal human colonic tumor xenografts, and small nodular tumors in the liver and lungs. Using intact MAbs (NP-4 and Mu-9), clearance of background radioactivity was delayed to 3-7 days post-treatment. Treatment with F(ab')2 and Fab' fragments of both NP-4 and Mu-9 MAbs, however, promoted clearance of background 125I-radioactivity which was well advanced by 6-24 h and complete by 24-48 h after injection. Localization of 125I-radioactivity in large and micrometastatic tumor perimeters was the most characteristic uptake pattern observed for both intact and fragmented MAbs. Qualitative analysis of macroautoradiographic images and quantitative densitometry indicated that the higher tumor-to-blood ratios achieved with labeled F(ab')2 and Fab' fragments at early time points, compared to labeled whole immunoglobulin, appeared to be more a function of rapid plasma clearance, tumor mass, location of xenografts and specific tumor growth patterns than increased tumor penetrance by lower molecular weight univalent and bivalent immune fragments.
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Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Sharkey
R M
RM
Grundy
J P
JP
Goldenberg
D M
DM
D015502:Absorptiometry, Photon; D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D001345:Autoradiography; D003110:Colonic Neoplasms / Q000276:immunology*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D009362:Neoplasm Metastasis
D000912:Antibodies, Neoplasm; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes