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Biodistribution and pharmacokinetics of 125 I‐labeled monoclonal antibody M75 specific for carbonic anhydrase IX, an intrinsic marker of hypoxia, in nude mice xenografted with human colorectal carcinoma
Author(s) -
Chrastina Adrián,
Závada Jan,
Parkkila Seppo,
Kaluz Štefan,
Kaluzová Milota,
Rajčáni Július,
Pastorek Jaromír,
Pastoreková Silvia
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11142
Subject(s) - biodistribution , radioimmunotherapy , monoclonal antibody , pharmacokinetics , tumor hypoxia , in vivo , internalization , biology , microbiology and biotechnology , antibody , cancer research , in vitro , pathology , medicine , pharmacology , immunology , cell , biochemistry , radiation therapy
Carbonic anhydrase IX (CA IX) is frequently expressed in human carcinomas and absent from the corresponding normal tissues. Strong induction by tumor hypoxia predisposes CA IX to serve as a target for cancer diagnostics and therapy. Here we evaluated targeting properties and pharmacokinetics of CA IX‐specific monoclonal antibody (MAb) M75. Binding parameters of 125 I‐labeled M75, including equilibrium dissociation constant, hypoxia‐related binding to various cell lines and internalization, were analyzed in vitro . Biodistribution of 125 I‐M75 in nude mice bearing HT‐29 human colorectal carcinoma xenografts with hypoxic pattern of CA IX expression was studied by measurements of radioactivity in dissected tissues and macroautoradiography of tissue sections. Pharmacokinetics of intravenously administered 125 I‐M75 was described using a 2‐compartment model. Blood clearance showed a distribution phase t 1/2 (α) = 3.4 hr and an elimination phase t 1/2 (β) = 55.3 hr postinjection. Despite predominant CA IX localization in less accessible perinecrotic regions, 125 I‐M75 exhibited specific accumulation in xenograft, with a mean uptake of 15.3 ± 3.6% of injected dose per gram of tumor tissue at 48 hr postadministration. Specificity of M75 localization was confirmed by low tumor uptake of control antibody. Altogether, our data demonstrate that M75 MAb is a promising tool for selective immunotargeting of hypoxic human tumors that express CA IX. © 2003 Wiley‐Liss, Inc.