NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

Show details

124I-Chimeric monoclonal antibody G250

, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD

Created: ; Last Update: May 20, 2010.

Chemical name:124I-Chimeric monoclonal antibody G250
Abbreviated name:124I-cG250
Agent category:Antibody
Target:Carbonic anhydrase IX
Target category:Enzyme
Method of detection:Positron emission tomography (PET)
Source of signal:124I
  • Checkbox In vitro
  • Checkbox Rodents
  • Checkbox Humans
Click on protein, nucleotide (RefSeq), and gene for more information about human carbonic anhydrase IX.



In a variety of solid tumors, hypoxia was found to lead to tumor progression and the resistance of tumors to chemotherapy and radiotherapy (1-3). Tumor oxygenation is heterogeneously distributed within human tumors (4). Hypoxia in malignant tumors is thought to be a major factor limiting the efficacy of chemotherapy and radiotherapy. It would be beneficial to assess tumor oxygenation before and after therapy to provide an evaluation of tumor response to treatment and an insight into new therapeutic treatments (5). Tumor oxygenation is measured invasively using computerized polarographic oxygen-sensitive electrodes, which is regarded as the gold standard (6). Functional and non-invasive imaging of intratumoral hypoxia has been demonstrated to be feasible for the measurement of tumor oxygenation (7). This has led to the search for and development of hypoxia-targeted, non-invasive markers of tumor hypoxia.

Chapman proposed the use of 2-nitroimidazoles for hypoxia imaging (8). 2-Nitroimidazole compounds are postulated to undergo reduction in hypoxic condition, forming highly reactive oxygen radicals that subsequently bind covalently to macromolecules inside the cells (9). [18F]Fluoromisonidazole ([18F]FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia (7). Carbonic anhydrase (CA) IX is one of the most overexpressed genes in cells under hypoxic conditions (10). It is a transmembrane glycoprotein with CA activity in the extracellular domain, and it is found to be overexpressed in renal cell, cervical, lung, and colorectal tumors. Murine monoclonal antibody G250 against CA IX has been developed for in vitro and in vivo localization of CA IX in cells (11-13). G250 is found to bind to >94% of human clear-cell renal carcinoma. A murine-human chimeric G250 (cG250) has been generated to be less immunogenic in humans (14). 124I-cG250 has been evaluated as a PET imaging agent for renal cell carcinoma in mice (15) and patients (16).



The cG250 antibody (~2 nmol) was labeled with 4 MBq (0.108 mCi) 124I in the presence of Iodogen (15). 124I-cG250 was isolated with size-exclusion column chromatography with a radiolabeling efficiency of 67% and a specific activity of 6.2 MBq/nmol (0.16 mCi/nmol). Thin-layer chromatography revealed >97% of 124I was bound to cG250. 124I-cG250 exhibited an immunoreactivity of 95%.

In Vitro Studies: Testing in Cells and Tissues


Lawrentschuk et al. (15) performed binding experiments with 124I-cG250 in SK-RC-52 human renal carcinoma cells. The dissociation constant was found to be 2.2 nM with 400,000 antibody molecules per cell.

Animal Studies



Lawrentschuk et al. (15) studied the biodistribution of 124I-cG250 in mice (n = 5/group) bearing SK-RC-52 tumors at days 0 (2 h), 2, 3, and 7 after injection. The tracer accumulation in the tumors was 9.6%, 23.5%, 19.4%, and 7.4% injected dose per gram (ID/g), respectively. The liver and kidneys had lower radioactivity levels than the tumors at days 2–7. The radioactivity in the blood decreased from 32.2% ID/g (day 0) to 0.5% ID/g (day 7). The tumor/blood ratios were 5.0 and 31.0 on day 3 and day 7, respectively. The blood clearance pattern exhibited a two-phase model with a half-life of 2.6 h during the distribution phase and a half-life of 40.5 h during the elimination phase. The control antibody 124I-huA33 exhibited very low tumor accumulation. No blocking experiment was performed.

PET imaging with 124I-cG250 showed localization in the tumors and relatively low activity elsewhere in the mice at 24 h after injection. There was a significant correlation (r2 = 0.93, P < 0.0001) between tumor standard uptake values measured with PET and ex vivo measurement (% ID/g). Histoimmunostaining showed CA IX was distributed evenly in the viable tumor cells of the tumor sections.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available.

Human Studies


Divgi et al. (16) performed PET imaging with 124I-cG250 in 25 patients with renal masses who were scheduled to undergo surgical resection by laparotomy received a single intravenous infusion of 185 MBq (5 mCi (66 nmol)) 124I-cG250 over 20 min in this open-label pilot study. The obtained images were graded as positive (defined as a tumor/healthy kidney ratio >3). Fifteen of 16 clear-cell carcinomas were identified accurately with PET, and all nine non–clear-cell renal masses were negative for the tracer. The sensitivity of 124I-cG250 PET for clear-cell kidney carcinoma was 94%; the negative predictive value was 90%, and specificity and positive predictive accuracy were both 100%.


Serkies K., Jassem J. Chemotherapy in the primary treatment of cervical carcinoma. Crit Rev Oncol Hematol. 2005;54(3):197–208. [PubMed: 15890269]
Vaupel P., Mayer A. Hypoxia and anemia: effects on tumor biology and treatment resistance. Transfus Clin Biol. 2005;12(1):5–10. [PubMed: 15814285]
Rajendran J.G., Krohn K.A. Imaging hypoxia and angiogenesis in tumors. Radiol Clin North Am. 2005;43(1):169–87. [PubMed: 15693655]
Vaupel P., Harrison L. Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist. 2004;9 Suppl 5:4–9. [PubMed: 15591417]
Dehdashti F., Grigsby P.W., Mintun M.A., Lewis J.S., Siegel B.A., Welch M.J. Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: relationship to therapeutic response-a preliminary report. Int J Radiat Oncol Biol Phys. 2003;55(5):1233–8. [PubMed: 12654432]
Raleigh J.A., Dewhirst M.W., Thrall D.E. Measuring Tumor Hypoxia. Semin Radiat Oncol. 1996;6(1):37–45. [PubMed: 10717160]
Foo S.S., Abbott D.F., Lawrentschuk N., Scott A.M. Functional imaging of intratumoral hypoxia. Mol Imaging Biol. 2004;6(5):291–305. [PubMed: 15380739]
Chapman J.D. Hypoxic sensitizers--implications for radiation therapy. N Engl J Med. 1979;301(26):1429–32. [PubMed: 229413]
Chapman J.D., Baer K., Lee J. Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. Cancer Res. 1983;43(4):1523–8. [PubMed: 6831401]
Loncaster J.A., Harris A.L., Davidson S.E., Logue J.P., Hunter R.D., Wycoff C.C., Pastorek J., Ratcliffe P.J., Stratford I.J., West C.M. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res. 2001;61(17):6394–9. [PubMed: 11522632]
Lam J.S., Pantuck A.J., Belldegrun A.S., Figlin R.A. G250: a carbonic anhydrase IX monoclonal antibody. Curr Oncol Rep. 2005;7(2):109–15. [PubMed: 15717944]
Oosterwijk E., Debruyne F.M. Radiolabeled monoclonal antibody G250 in renal-cell carcinoma. World J Urol. 1995;13(3):186–90. [PubMed: 7550393]
Grabmaier K., Vissers J.L., De Weijert M.C., Oosterwijk-Wakka J.C., Van Bokhoven A., Brakenhoff R.H., Noessner E., Mulders P.A., Merkx G., Figdor C.G., Adema G.J., Oosterwijk E. Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250. Int J Cancer. 2000;85(6):865–70. [PubMed: 10709109]
Ahlskog J.K., Schliemann C., Marlind J., Qureshi U., Ammar A., Pedley R.B., Neri D. Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours. Br J Cancer. 2009;101(4):645–57. [PMC free article: PMC2736829] [PubMed: 19623173]
Lawrentschuk, N., F.T. Lee, G. Jones, A. Rigopoulos, A. Mountain, G. O'Keefe, A.T. Papenfuss, D.M. Bolton, I.D. Davis, and A.M. Scott, Investigation of hypoxia and carbonic anhydrase IX expression in a renal cell carcinoma xenograft model with oxygen tension measurements and (124)I-cG250 PET/CT. Urol Oncol, 2009. [PubMed: 19523858]
Divgi C.R., Pandit-Taskar N., Jungbluth A.A., Reuter V.E., Gonen M., Ruan S., Pierre C., Nagel A., Pryma D.A., Humm J., Larson S.M., Old L.J., Russo P. 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. Lancet Oncol. 2007;8(4):304–10. [PubMed: 17395103]
PubReader format: click here to try


Search MICAD

Limit my Search:

Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed

Related citations in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...