Engineering of Affibody molecules for Radionuclide Molecular Imaging and Intracellular Targeting

摘要: PURPOSE: Radionuclide imaging of insulin-like growth factor type 1 receptor (IGF-1R) expression in tumours might be used for selection patients who would benefit from IGF-1R-targeted therapy. We have previously shown the feasibility IGF-1R using Affibody molecule (111)In-DOTA-His(6)-Z(IGF1R:4551). The use (99m)Tc instead (111)In should improve sensitivity and resolution imaging, reduce dose burden to patients. hypothesized that inclusion a HEHEHE tag His(6) Z(IGF1R:4551) permit its convenient purification IMAC, enable labelling with [(99m)Tc(CO)(3)](+), biodistribution. METHODS: was expressed N terminus. resulting (HE)(3)-Z(IGF1R:4551) construct labelled [(99m)Tc(CO)(3)](+). Targeting IGF-1R-expressing cells [(99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) evaluated vitro vivo. RESULTS: stably preserved specific binding DU-145 prostate cancer vitro. In mice, accumulated organs (pancreas, stomach, lung salivary gland). demonstrated 3.6-fold lower accumulation liver spleen than (111)In-DOTA-Z(IGF1R:4551). NMRI nu/nu mice xenografts, tumour uptake 1.32 ± 0.11 %ID/g tumour-to-blood ratio 4.4 0.3 at 8 h after injection. xenografts were visualized gamma camera 6 CONCLUSION: (99m)Tc(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) is promising candidate visualization malignant tumours.