Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma

  • Authors:
    • Marc-André Fortin
    • Anna Orlova
    • Per-Uno Malmström
    • Vladimir Tolmachev
  • View Affiliations

  • Published online on: February 1, 2007     https://doi.org/10.3892/ijmm.19.2.285
  • Pages: 285-291
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Abstract

The direct instillation of radiolabelled conjugates in the urinary bladder is a promising path for the treatment of bladder carcinoma. The targeting of HER2/neu receptors expressed on the surface of many bladder carcinoma cells shows potential to be developed as a therapeutic strategy, and patients identified with a high risk of progression may benefit from adjuvant targeted radionuclide therapy. A phage-display selected Affibody molecule (ZHER2:342) which binds to HER2/neu with picomolar affinity, can be used for targeting HER2/neu-expressing bladder carcinomas. A DOTA-derivative of ZHER2:342, designated as DOTA-ZHER2:342-3, is considered as a suitable targeting agent for therapy. The DOTA chelator provides stable labelling with radiometals, and the low molecular weight (7.2 kDa) of the DOTA-ZHER2:342-3 compound is expected to enable efficient tumor penetration. DOTA-ZHER2:342-3 was radiolabelled with 90Y and 177Lu in 1 M ammonium acetate buffer, at pH 5.5, and in the presence of ascorbic acid. Nearly quantitative labelling yields were achieved for both nuclides after 15 min of incubation at 60°C. After chelation, the conjugates retained their capacity to specifically bind to HER2/neu-expressing SKOV-3 cells. The radiolabelled affibody conjugate (DOTA-ZHER2:342-3) demonstrated high antigen-binding capacity and good cellular retention. Biodistribution in normal mice demonstrated low uptake in all organs and tissues except for kidneys.

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February 2007
Volume 19 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Fortin M, Orlova A, Malmström P and Tolmachev V: Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma. Int J Mol Med 19: 285-291, 2007
APA
Fortin, M., Orlova, A., Malmström, P., & Tolmachev, V. (2007). Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma. International Journal of Molecular Medicine, 19, 285-291. https://doi.org/10.3892/ijmm.19.2.285
MLA
Fortin, M., Orlova, A., Malmström, P., Tolmachev, V."Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma". International Journal of Molecular Medicine 19.2 (2007): 285-291.
Chicago
Fortin, M., Orlova, A., Malmström, P., Tolmachev, V."Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody molecule, a candidate agent for locoregional treatment of urinary bladder carcinoma". International Journal of Molecular Medicine 19, no. 2 (2007): 285-291. https://doi.org/10.3892/ijmm.19.2.285