title: PET imaging of insulin-like growth factor type 1 receptor expression with a 64Cu-labeled Affibody molecule.
abstract: The insulin-like growth factor 1 receptor (IGF-1R) serves as an attractive target for cancer molecular imaging and therapy. Previous single photon emission computerized tomography (SPECT) studies showed that the IGF-1R-targeting Affibody molecules (99m)Tc-ZIGF1R:4551-GGGC, [(99m)Tc(CO)3](+)-(HE)3-ZIGF1R:4551 and (111)In-DOTA-ZIGF1R:4551 can discriminate between high and low IGF-1R-expression tumors and have the potential for patient selection for IGF-1R-targeted therapy. Compared with SPECT, positron emission tomography (PET) may improve imaging of IGF-1R-expression, because of its high sensitivity, high spatial resolution, strong quantification ability. The aim of the present study was to develop the (64)Cu-labeled NOTA-conjugated Affibody molecule ZIGF-1R:4:40 as a PET probe for imaging of IGF-1R-positive tumor. An Affibody analogue (Ac-Cys-ZIGF-1R:4:40) binding to IGF-1R was site-specifically conjugated with NOTA and labeled with (64)Cu. Binding affinity and specificity of (64)Cu-NOTA-ZIGF-1R:4:40 to IGF-1R were evaluated using human glioblastoma U87MG cells. Small-animal PET, biodistribution, and metabolic stability studies were conducted on mice bearing U87MG xenografts after the injection of (64)Cu-NOTA-ZIGF-1R:4:40 with or without co-injection of unlabeled Affibody proteins. The radiosynthesis of (64)Cu-NOTA-ZIGF-1R:4:40 was completed successfully within 60 min with a decay-corrected yield of 75 %. (64)Cu-NOTA-ZIGF-1R:4:40 bound to IGF-1R with low nanomolar affinity (K D = 28.55 ± 3.95 nM) in U87MG cells. (64)Cu-NOTA-ZIGF-1R:4:40 also displayed excellent in vitro and in vivo stability. In vivo biodistribution and PET studies demonstrated targeting of U87MG gliomas xenografts was IGF-1R specific. The tumor uptake was 5.08 ± 1.07 %ID/g, and the tumor to muscle ratio was 11.89 ± 2.16 at 24 h after injection. Small animal PET imaging studies revealed that (64)Cu-NOTA-ZIGF-1R:4:40 could clearly identify U87MG tumors with good contrast at 1-24 h after injection. This study demonstrates that (64)Cu-NOTA-ZIGF-1R:4:40 is a promising PET probe for imaging IGF-1R positive tumor.
authors: Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen, China.
authors: Xinhui
authors: X
authors: Su
authors: Kai
authors: K
authors: Cheng
authors: Yang
authors: Y
authors: Liu
authors: Xiang
authors: X
authors: Hu
authors: Shuxian
authors: S
authors: Meng
authors: Zhen
authors: Z
authors: Cheng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D014408:Biomarkers, Tumor; D003301:Copper Radioisotopes; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D013205:Staphylococcal Protein A; D017526:Receptor, IGF Type 1