Biodistribution and pharmacokinetics of 125I-labeled monoclonal antibody M75 specific for carbonic anhydrase IX, an intrinsic marker of hypoxia, in nude mice xenografted with human colorectal carcinoma

0191628 - UMG-J 20033136 RIV US eng J - Článek v odborném periodiku
Chrastina, A. - Závada, Jan - Parkkila, S. - Kaluz, Š. - Kaluzová, M. - Rajcani, J. - Pastorek, J. - Pastorekova, S.
Biodistribution and pharmacokinetics of 125I-labeled monoclonal antibody M75 specific for carbonic anhydrase IX, an intrinsic marker of hypoxia, in nude mice xenografted with human colorectal carcinoma.
International Journal of Cancer. Roč. 105, č. 4 (2003), s. 873-881. ISSN 0020-7136. E-ISSN 1097-0215
Grant CEP: GA MZd 45362
Výzkumný záměr: CEZ:AV0Z5052915
Klíčová slova: carbonic anhydrase IX
Kód oboru RIV: FD - Onkologie a hematologie
Impakt faktor: 4.375, rok: 2003

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)(alpha) = 3.4 hr and an elimination phase t(1/2)(beta) = 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.
Trvalý link: http://hdl.handle.net/11104/0087366