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

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-Z_IGF1R: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 Z_IGF1R: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-Z_IGF1R:4551 construct was labelled with [^99mTc(CO)₃]⁺. Targeting of IGF-1R-expressing cells using [^99mTc(CO)₃]⁺-(HE) ₃-Z_IGF1R:4551 was evaluated in vitro and in vivo. Results: (HE)₃-Z_IGF1R: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-Z_IGF1R: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-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: ^99mTc(CO)₃]⁺-(HE) ₃-Z_IGF1R:4551 is a promising candidate for visualization of IGF-1R expression in malignant tumours.

Original language	English
Pages (from-to)	439-449
Number of pages	11
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	40
Issue number	3
DOIs	https://doi.org/10.1007/s00259-012-2284-8
Publication status	Published - Feb 2013
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1007/s00259-012-2284-8

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Orlova, A., Hofström, C., Strand, J., Varasteh, Z., Sandstrom, M., Andersson, K., Tolmachev, V., & Gräslund, T. (2013). ⁺-(HE)₃-Z_IGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours. European Journal of Nuclear Medicine and Molecular Imaging, 40(3), 439-449. https://doi.org/10.1007/s00259-012-2284-8

⁺-(HE)₃-Z_IGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours. / Orlova, Anna; Hofström, Camilla; Strand, Joanna; Varasteh, Zohreh; Sandstrom, Mattias; Andersson, Karl; Tolmachev, Vladimir; Gräslund, Torbjörn.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 40, No. 3, 02.2013, p. 439-449.

Research output: Contribution to journal › Article › peer-review

Orlova, A, Hofström, C, Strand, J, Varasteh, Z, Sandstrom, M, Andersson, K, Tolmachev, V & Gräslund, T 2013, '⁺-(HE)₃-Z_IGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours', European Journal of Nuclear Medicine and Molecular Imaging, vol. 40, no. 3, pp. 439-449. https://doi.org/10.1007/s00259-012-2284-8

Orlova, Anna ; Hofström, Camilla ; Strand, Joanna ; Varasteh, Zohreh ; Sandstrom, Mattias ; Andersson, Karl ; Tolmachev, Vladimir ; Gräslund, Torbjörn. / ⁺-(HE)₃-Z_IGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours. In: European Journal of Nuclear Medicine and Molecular Imaging. 2013 ; Vol. 40, No. 3. pp. 439-449.

@article{0f3c84af310d4085ab9d74b8387ca122,

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

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.",

keywords = "Affibody molecules, Biodistribution, HEHEHE tag, IGF-1R, Molecular imaging, Technetium-99m",

author = "Anna Orlova and Camilla Hofstr{\"o}m and Joanna Strand and Zohreh Varasteh and Mattias Sandstrom and Karl Andersson and Vladimir Tolmachev and Torbj{\"o}rn Gr{\"a}slund",

note = "Funding Information: 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 (Vetenskapsr{\aa}det) and the Magn. Bergvall foundation. Copyright: Copyright 2013 Elsevier B.V., All rights reserved.",

year = "2013",

month = feb,

doi = "10.1007/s00259-012-2284-8",

language = "English",

volume = "40",

pages = "439--449",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer Verlag",

number = "3",

}

TY - JOUR

T1 - +-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

AU - Orlova, Anna

AU - Hofström, Camilla

AU - Strand, Joanna

AU - Varasteh, Zohreh

AU - Sandstrom, Mattias

AU - Andersson, Karl

AU - Tolmachev, Vladimir

AU - Gräslund, Torbjörn

N1 - Funding Information: 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. Copyright: Copyright 2013 Elsevier B.V., All rights reserved.

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - Affibody molecules

KW - Biodistribution

KW - HEHEHE tag

KW - IGF-1R

KW - Molecular imaging

KW - Technetium-99m

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JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

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