[99mTc(CO)3]+-(HE)3-Z IGF1R45514551: a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours.
2013 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 40, no 3, 439-449 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 40, no 3, 439-449 p.
Affibody molecules, affinity proteins, radionuclide molecular imaging, intracellular targeting, EGFR, HER2, IGF-1R
Radiology, Nuclear Medicine and Medical Imaging
IdentifiersURN: urn:nbn:se:kth:diva-116887DOI: 10.1007/s00259-012-2284-8ISI: 000314676900015PubMedID: 23179942ScopusID: 2-s2.0-84873997284OAI: oai:DiVA.org:kth-116887DiVA: diva2:601422
FunderSwedish Research Council
QC 201302142013-01-292013-01-292013-03-08Bibliographically approved