[99mTc(CO)3]+-(HE)3-ZIGF1R:4551, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

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.