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[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Radionuclide imaging of insulin-like growth factor type 1 receptor (IGF-1R) expression in tumours might be used for selection of patients who would benefit from IGF-1R-targeted therapy. We have previously shown the feasibility of IGF-1R imaging using the Affibody molecule 111In-DOTA-His6-ZIGF1R:4551. The use of 99mTc instead of 111In should improve sensitivity and resolution of imaging, and reduce the dose burden to patients. We hypothesized that inclusion of a HEHEHE tag instead of a His6 tag in ZIGF1R:4551 would permit its convenient purification using IMAC, enable labelling with [99mTc(CO)3]+, and improve its biodistribution.

Methods

ZIGF1R:4551 was expressed with a HEHEHE tag in the N terminus. The resulting (HE)3-ZIGF1R:4551 construct was labelled with [99mTc(CO)3]+. Targeting of IGF-1R-expressing cells using [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 was evaluated in vitro and in vivo.

Results

(HE)3-ZIGF1R:4551 was stably labelled with 99mTc with preserved specific binding to IGF-1R-expressing DU-145 prostate cancer cells in vitro. In mice, [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 accumulated in IGF-1R-expressing organs (pancreas, stomach, lung and salivary gland). [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 demonstrated 3.6-fold lower accumulation in the liver and spleen than 111In-DOTA-ZIGF1R:4551. In NMRI nu/nu mice with DU-145 prostate cancer xenografts, the tumour uptake was 1.32 ± 0.11 %ID/g and the tumour-to-blood ratio was 4.4 ± 0.3 at 8 h after injection. The xenografts were visualized using a gamma camera 6 h after injection.

Conclusion

99mTc(CO)3]+-(HE)3-ZIGF1R:4551 is a promising candidate for visualization of IGF-1R expression in malignant tumours.

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Acknowledgments

We would like to thank Tove Alm and Robert Karlsson for expert technical assistance in performing the binding measurements by SPR. This research was supported financially by grants from the Swedish Cancer Society (Cancerfonden), the Swedish Research Council (Vetenskapsrådet) and the Magn. Bergvall foundation.

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Authors and Affiliations

  1. Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden

    Anna Orlova & Zohreh Varasteh

  2. Division of Molecular Biotechnology, School of Biotechnology, Royal Institute of Technology, Stockholm, Sweden

    Camilla Hofström & Torbjörn Gräslund

  3. Division of Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden

    Joanna Strand, Karl Andersson & Vladimir Tolmachev

  4. Medical Physics, Department of Oncology, Uppsala University Hospital, Uppsala, Sweden

    Mattias Sandstrom

  5. Ridgeview Instruments AB, Uppsala, Sweden

    Karl Andersson

  6. Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden

    Vladimir Tolmachev

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  1. Anna Orlova
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Correspondence to Vladimir Tolmachev.

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Orlova, A., Hofström, C., Strand, J. et al. [99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours. Eur J Nucl Med Mol Imaging 40, 439–449 (2013). https://doi.org/10.1007/s00259-012-2284-8

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  • DOI: https://doi.org/10.1007/s00259-012-2284-8

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