Preliminary biological evaluation of 125I-labeled anti-carbonic anhydrase IX monoclonal antibody in the mice bearing HT-29 tumors

ObjectiveTo evaluate 125I-labeled anti-carbonic anhydrase IX monoclonal antibody (125I-MAb) as a novel single-photon emission computed tomography tracer for imaging carbonic anhydrase IX in the mice bearing HT-29 tumors. MethodsAnti-carbonic anhydrase IX monoclonal antibody was labeled with iodine-125 by the iodogen method. The radiochemical purity of 125I-MAb was measured by radio-thin-layer chromatography. The in-vitro stability of 125I-MAb was determined in PBS (0.05 mol/l, pH 7.4) or new-born calf serum at 37°C, and analyzed by radio-thin-layer chromatography. A biodistribution study and planar imaging were carried out in the mice bearing HT-29 tumors. The expression of CA IX in HT-29 tumors was analyzed by immunohistochemistry. Results125I-MAb was obtained with a radiolabeling efficiency of 98%, and showed high stability in PBS and new-born calf serum. Furthermore, the biodistribution study showed specific tumor uptake in the mice bearing HT-29 tumors, and planar imaging with 125I-MAb 48 h post injection showed a high concentration of radioactivity in tumors and a much decreased concentration in tumors in the blocking group. An immunohistochemical analysis showed the expression of CA IX in HT-29 tumors. ConclusionThe preliminary biodistribution study and results from planar imaging showed the potential of 125I-MAb as an agent for tumor diagnosis and encouraged further investigation.

[1]  K. Milde-Langosch,et al.  Carbonic anhydrase IX in tumor tissue and sera of patients with primary cervical cancer , 2011, BMC Cancer.

[2]  P. Lambin,et al.  Synthesis and biological evaluation of a 99mTc-labelled sulfonamide conjugate for in vivo visualization of carbonic anhydrase IX expression in tumor hypoxia. , 2010, Nuclear medicine and biology.

[3]  Valerie A Longo,et al.  Molecular Targeting of Carbonic Anhydrase IX in Mice with Hypoxic HT29 Colorectal Tumor Xenografts , 2010, PloS one.

[4]  J. Pouysségur,et al.  High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer , 2010, British Journal of Cancer.

[5]  C. Supuran,et al.  S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases. , 2009, Journal of medicinal chemistry.

[6]  H. Minn,et al.  Expression of carbonic anhydrase IX suggests poor outcome in rectal cancer , 2009, British Journal of Cancer.

[7]  N. Rioux-Leclercq,et al.  Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma , 2008, International journal of cancer.

[8]  Richard D. Vaughan-Jones,et al.  Regulation of tumor pH and the role of carbonic anhydrase 9 , 2007, Cancer and Metastasis Reviews.

[9]  J. Humm,et al.  Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial. , 2007, The Lancet. Oncology.

[10]  C. Supuran,et al.  Hypoxia activates the capacity of tumor‐associated carbonic anhydrase IX to acidify extracellular pH , 2004, FEBS letters.

[11]  P. Malfertheiner,et al.  Expression of carbonic anhydrase IX in human pancreatic cancer , 2003, Alimentary pharmacology & therapeutics.

[12]  W. Oyen,et al.  Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[13]  W. Oyen,et al.  Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  S. Pastoreková,et al.  A novel quasi-viral agent, MaTu, is a two-component system. , 1992, Virology.

[15]  J. Pouysségur,et al.  Hypoxia-inducible carbonic anhydrase IX and XII promote tumor cell growth by counteracting acidosis through the regulation of the intracellular pH. , 2009, Cancer research.