Evaluation of a radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression

  • Authors:
    • Maria Rosestedt
    • Ken G. Andersson
    • Bogdan Mitran
    • Sara S. Rinne
    • Vladimir Tolmachev
    • John Löfblom
    • Anna Orlova
    • Stefan Ståhl
  • View Affiliations

  • Published online on: October 11, 2017     https://doi.org/10.3892/ijo.2017.4152
  • Pages:1765-1774
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Abstract

The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated. Preclinical studies have shown that the contrast when imaging using anti-HER3 affibody molecules can be improved over time. We aim to develop an agent for PET imaging of HER3 expression using the long-lived positron-emitting radionuclide cobalt-55 (55Co) (T1/2=17.5 h). A long-lived cobalt isotope 57Co was used as a surrogate for 55Co in this study. The anti-HER3 affibody molecule HEHEHE-ZHER3-NOTA was labelled with radiocobalt with high yield, purity and stability. Biodistribution of 57Co-HEHEHE-ZHER3-NOTA was measured in mice bearing DU145 (prostate carcinoma) and LS174T (colorectal carcinoma) xenografts at 3 and 24 h post injection (p.i.). Tumour-to-blood ratios significantly increased between 3 and 24 h p.i. (p<0.05). At 24 h p.i., tumour-to-blood ratios were 6 for DU145 and 8 for LS174T xenografts, respectively. HER3‑expressing xenografts were clearly visualized in a preclinical imaging setting already 3 h p.i., and contrast further improved at 24 h p.i. In conclusion, the radiocobalt-labelled anti-HER3 affibody molecule, HEHEHE-ZHER3-NOTA, is a promising tracer for imaging of HER3 expression in tumours.

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December 2017
Volume 51 Issue 6

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

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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APA
Rosestedt, M., Andersson, K.G., Mitran, B., Rinne, S.S., Tolmachev, V., Löfblom, J. ... Ståhl, S. (2017). Evaluation of a radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression. International Journal of Oncology, 51, 1765-1774. https://doi.org/10.3892/ijo.2017.4152
MLA
Rosestedt, M., Andersson, K. G., Mitran, B., Rinne, S. S., Tolmachev, V., Löfblom, J., Orlova, A., Ståhl, S."Evaluation of a radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression". International Journal of Oncology 51.6 (2017): 1765-1774.
Chicago
Rosestedt, M., Andersson, K. G., Mitran, B., Rinne, S. S., Tolmachev, V., Löfblom, J., Orlova, A., Ståhl, S."Evaluation of a radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression". International Journal of Oncology 51, no. 6 (2017): 1765-1774. https://doi.org/10.3892/ijo.2017.4152