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

Anna Orlova, Camilla Hofström, Joanna Strand, Zohreh Varasteh, Mattias Sandstrom, Karl Andersson, Vladimir Tolmachev, Torbjörn Gräslund

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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: Z IGF1R: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-Z IGF1R: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.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume40
Issue number3
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Keywords

  • Affibody molecules
  • Biodistribution
  • HEHEHE tag
  • IGF-1R
  • Molecular imaging
  • Technetium-99m

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of '<sup>+</sup>-(HE)<sub>3</sub>-Z<sub>IGF1R:4551</sub>, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours'. Together they form a unique fingerprint.

Cite this