title: A two-step strategy to radiolabel choline phospholipids with99mTc in S180 cell membranes via strain-promoted cyclooctyne-azide cycloaddition reaction.
abstract: As tumor markers, the radiolabeling of choline (Cho)-containing phospholipids in cellular membranes with99mTc is a challenge. The conventional strategy to combine the metallic radionuclide with Cho by large ligand damages the bioactivity of Cho, resulting in low tumor-to-nontumor ratios. Pretargeting strategy based on strain-promoted cyclooctyne-azide cycloaddition (SPAAC) reaction was applied to solve this general problem. Functional click synthons were synthesized as pretargeting components: azidoethyl-choline (AECho) serves as tumor marker and azadibenzocyclooctyne (ADIBO) conjugated to bis(2-pieolyl) amine (BPA) ligand (ADIBO-BPA) as99mTc(CO)3-labeling and azido-binding group. Both in vitro cell experiment and in vivo biodistribution experiment indicate that it is versatile to radiolabel Cho in cellular membranes via this two-step pretargeting strategy. We believe that this pretargeting strategy can indeed enhance the target-specificity and also reduce background signals to optimize imaging quality.
authors: Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors: Qingxin
authors: Q
authors: Chen
authors: Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: twchu@pku.edu.cn.
authors: Taiwei
authors: T
authors: Chu
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D001386:Azides / Q000737:chemistry*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry*; D002794:Choline / Q000032:analysis*; D057930:Click Chemistry; D061565:Cycloaddition Reaction; D034242:Cyclooctanes / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis*; D015609:Organotechnetium Compounds / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D000588:Amines; D001386:Azides; D034242:Cyclooctanes; D008024:Ligands; D015609:Organotechnetium Compounds; D010743:Phospholipids; D002794:Choline
keywords: (99m)Tc(CO)(3)-labeling; ADIBO-BPA; AECho; Pretargeting; SPAAC; Tumor imaging