Open Access

Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 Affibody molecule

  • Authors:
    • Hadis Honarvar
    • Javad Garousi
    • Elin Gunneriusson
    • Ingmarie Höidén-Guthenberg
    • Mohamed Altai
    • Charles Widström
    • Vladimir Tolmachev
    • Fredrik Y. Frejd
  • View Affiliations

  • Published online on: November 27, 2014     https://doi.org/10.3892/ijo.2014.2782
  • Pages: 513-520
  • Copyright: © Honarvar et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme involved in regulation of tissue pH balance. In cancer, CAIX expression is associated with tumor hypoxia. CAIX is also overexpressed in renal cell carcinoma and is a molecular target for the therapeutic antibody cG250 (girentuximab). Radionuclide imaging of CAIX expression might be used for identification of patients who may benefit from cG250 therapy and from treatment strategies for hypoxic tumors. Affibody molecules are small (7 kDa) scaffold proteins having a high potential as probes for radionuclide molecular imaging. The aim of the present study was to evaluate feasibility of in vivo imaging of CAIX-expression using radiolabeled Affibody molecules. A histidine-glutamate-histidine-glutamate-histidine-glutamate (HE)3-tag-containing CAIX-binding Affibody molecule (HE)3-ZCAIX:1 was labeled with [99mTc(CO)3]+. Its binding properties were evaluated in vitro using CAIX-expressing SK-RC-52 renal carcinoma cells. 99mTc-(HE)3-ZCAIX:1 was evaluated in NMRI nu/nu mice bearing SK-RC-52 xenografts. The in vivo specificity test confirmed CAIX-mediated tumor targeting. 99mTc-(HE)3-ZCAIX:1 cleared rapidly from blood and normal tissues except for kidneys. At optimal time-point (4 h p.i.), the tumor uptake was 9.7±0.7% ID/g, and tumor-to-blood ratio was 53±10. Experimental imaging of CAIX-expressing SK-RC-52 xenografts at 4 h p.i. provided high contrast images. The use of radioiodine label for ZCAIX:1 enabled the reduction of renal uptake, but resulted in significantly lower tumor uptake and tumor-to-blood ratio. Results of the present study suggest that radiolabeled Affibody molecules are promising probes for imaging of CAIX-expression in vivo.
View Figures
View References

Related Articles

Journal Cover

February-2015
Volume 46 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Honarvar H, Garousi J, Gunneriusson E, Höidén-Guthenberg I, Altai M, Widström C, Tolmachev V and Frejd FY: Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 Affibody molecule. Int J Oncol 46: 513-520, 2015
APA
Honarvar, H., Garousi, J., Gunneriusson, E., Höidén-Guthenberg, I., Altai, M., Widström, C. ... Frejd, F.Y. (2015). Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 Affibody molecule. International Journal of Oncology, 46, 513-520. https://doi.org/10.3892/ijo.2014.2782
MLA
Honarvar, H., Garousi, J., Gunneriusson, E., Höidén-Guthenberg, I., Altai, M., Widström, C., Tolmachev, V., Frejd, F. Y."Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 Affibody molecule". International Journal of Oncology 46.2 (2015): 513-520.
Chicago
Honarvar, H., Garousi, J., Gunneriusson, E., Höidén-Guthenberg, I., Altai, M., Widström, C., Tolmachev, V., Frejd, F. Y."Imaging of CAIX-expressing xenografts in vivo using 99mTc-HEHEHE-ZCAIX:1 Affibody molecule". International Journal of Oncology 46, no. 2 (2015): 513-520. https://doi.org/10.3892/ijo.2014.2782