Localization by whole-body autoradiography of intact and fragmented radiolabeled antibodies in a metastatic human colonic cancer model

• Published in: International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology Vol. 19; no. 1; pp. 87,95 - 93,99
• Main Authors: Fand, Irwin, Sharkey, Robert M., Grundy, John P., Goldenberg, David M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1992; Pergamon
• Subjects: Absorptiometry, Photon; Animals; Antibodies, Neoplasm - immunology; Autoradiography; Biological and medical sciences; Colonic Neoplasms - immunology; Digestion. Liver. Biliary tract. Spleen. Pancreas; Female; Humans; Immunoglobulin Fab Fragments - immunology; Investigative techniques, diagnostic techniques (general aspects); Iodine Radioisotopes; Medical sciences; Mice; Mice, Nude; Molecular Weight; Neoplasm Metastasis; Radionuclide investigations; CSAp; MAbs; WBAR; IgG; RAID; RAIT; CEA; Radionuclide study; Tumoral marker; Monoclonal antibody; Malignant tumor; Experimental study; Iodine Complexes; In vitro; Uptake; Autoradiography; Animal; Distribution; Digestive diseases; F(ab')2-Fragment; Whole body; Colon; Radiopharmaceuticals; Comparative study
• ISSN: 0883-2897
• DOI: 10.1016/0883-2897(92)90190-A

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.