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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

Orlova, Anna ; Hofström, Camilla ; Strand, Joanna LU ; Varasteh, Zohreh ; Sandstrom, Mattias ; Andersson, Karl ; Tolmachev, Vladimir and Gräslund, Torbjörn (2013) In European Journal of Nuclear Medicine and Molecular Imaging 40(3). p.49-439
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 (111)In-DOTA-His(6)-Z(IGF1R:4551). The use of (99m)Tc instead of (111)In 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 His(6) tag in Z(IGF1R:4551) would permit its convenient purification using IMAC, enable labelling with [(99m)Tc(CO)(3)](+), and improve its biodistribution.

METHODS: Z(IGF1R:4551) was expressed with a HEHEHE tag in the N terminus.... (More)

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 (111)In-DOTA-His(6)-Z(IGF1R:4551). The use of (99m)Tc instead of (111)In 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 His(6) tag in Z(IGF1R:4551) would permit its convenient purification using IMAC, enable labelling with [(99m)Tc(CO)(3)](+), and improve its biodistribution.

METHODS: Z(IGF1R:4551) was expressed with a HEHEHE tag in the N terminus. The resulting (HE)(3)-Z(IGF1R:4551) construct was labelled with [(99m)Tc(CO)(3)](+). Targeting of IGF-1R-expressing cells using [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) was evaluated in vitro and in vivo.

RESULTS: (HE)(3)-Z(IGF1R:4551) was stably labelled with (99m)Tc with preserved specific binding to IGF-1R-expressing DU-145 prostate cancer cells in vitro. In mice, [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung and salivary gland). [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) demonstrated 3.6-fold lower accumulation in the liver and spleen than (111)In-DOTA-Z(IGF1R: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: (99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) is a promising candidate for visualization of IGF-1R expression in malignant tumours.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Cell Line, Tumor, Cell Transformation, Neoplastic, Drug Stability, Gene Expression Regulation, Neoplastic, Heterocyclic Compounds, 1-Ring/chemistry, Humans, Male, Mice, Prostatic Neoplasms/diagnostic imaging, Radionuclide Imaging, Receptor, IGF Type 1/metabolism, Recombinant Fusion Proteins/chemistry, Technetium
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
40
issue
3
pages
49 - 439
publisher
Springer
external identifiers
  • scopus:84873997284
  • pmid:23179942
ISSN
1619-7070
DOI
10.1007/s00259-012-2284-8
language
English
LU publication?
no
id
8b6bebb0-c93c-4922-9555-b92a2f5b3677
date added to LUP
2022-11-16 13:43:16
date last changed
2024-02-17 23:57:07
@article{8b6bebb0-c93c-4922-9555-b92a2f5b3677,
  abstract     = {{<p>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 (111)In-DOTA-His(6)-Z(IGF1R:4551). The use of (99m)Tc instead of (111)In 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 His(6) tag in Z(IGF1R:4551) would permit its convenient purification using IMAC, enable labelling with [(99m)Tc(CO)(3)](+), and improve its biodistribution.</p><p>METHODS: Z(IGF1R:4551) was expressed with a HEHEHE tag in the N terminus. The resulting (HE)(3)-Z(IGF1R:4551) construct was labelled with [(99m)Tc(CO)(3)](+). Targeting of IGF-1R-expressing cells using [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) was evaluated in vitro and in vivo.</p><p>RESULTS: (HE)(3)-Z(IGF1R:4551) was stably labelled with (99m)Tc with preserved specific binding to IGF-1R-expressing DU-145 prostate cancer cells in vitro. In mice, [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) accumulated in IGF-1R-expressing organs (pancreas, stomach, lung and salivary gland). [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) demonstrated 3.6-fold lower accumulation in the liver and spleen than (111)In-DOTA-Z(IGF1R: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.</p><p>CONCLUSION: (99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) is a promising candidate for visualization of IGF-1R expression in malignant tumours.</p>}},
  author       = {{Orlova, Anna and Hofström, Camilla and Strand, Joanna and Varasteh, Zohreh and Sandstrom, Mattias and Andersson, Karl and Tolmachev, Vladimir and Gräslund, Torbjörn}},
  issn         = {{1619-7070}},
  keywords     = {{Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Drug Stability; Gene Expression Regulation, Neoplastic; Heterocyclic Compounds, 1-Ring/chemistry; Humans; Male; Mice; Prostatic Neoplasms/diagnostic imaging; Radionuclide Imaging; Receptor, IGF Type 1/metabolism; Recombinant Fusion Proteins/chemistry; Technetium}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{49--439}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours}},
  url          = {{http://dx.doi.org/10.1007/s00259-012-2284-8}},
  doi          = {{10.1007/s00259-012-2284-8}},
  volume       = {{40}},
  year         = {{2013}},
}