Preclinical Evaluation of a New Format of Ga- and In-Labeled Affibody Molecule Z for the Visualization of IGF-1R Expression in Malignant Tumors Using PET and SPECT.

The Insulin-like growth factor-1 receptor (IGF-1R) is a molecular target for several monoclonal antibodies undergoing clinical evaluation as anticancer therapeutics. The non-invasive detection of IGF-1R expression in tumors might enable stratification of patients for specific treatment and improve the outcome of both clinical trials and routine treatment. The affibody molecule Z binds specifically to IGF-1R with subnanomolar affinity. The goal of this study was to evaluate the Ga and In-labeled affibody construct NODAGA-(HE)-Z for the imaging of IGF-1R expression, using PET and SPECT. The labeling was efficient and provided stable coupling of both radionuclides. The two imaging probes, [Ga]Ga-NODAGA-(HE)-Z and [In]In-NODAGA-(HE)-Z, demonstrated specific binding to IGF-1R-expressing human cancer cell lines in vitro and to IGF-1R-expressing xenografts in mice. Preclinical PET and SPECT/CT imaging demonstrated visualization of IGF-1R-expressing xenografts already one hour after injection. The tumor-to-blood ratios at 3 h after injection were 7.8 ± 0.2 and 8.0 ± 0.6 for [Ga]Ga-NODAGA-(HE)-Z and [In]In-NODAGA-(HE)-Z, respectively. In conclusion, a molecular design of the Z affibody molecule, including placement of a (HE)-tag on the N-terminus and site-specific coupling of a NODAGA chelator on the C-terminus, provides a tracer with improved imaging properties for visualization of IGF-1R in malignant tumors, using PET and SPECT.