Astatine-211 labeling of protein using TCP as a bi-functional linker: synthesis and preliminary evaluation in vivo and in vitro

• Published in: Journal of radioanalytical and nuclear chemistry Vol. 288; no. 1; pp. 71 - 77
• Main Authors: Yang, Yuanyou, Lin, Rushan, Liu, Ning, Liao, Jiali, Wei, Min, Jin, Jiannan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.04.2011
• Subjects: Biocompatibility; Biomedical materials; Chemistry; Chemistry and Materials Science; Diagnostic Radiology; Hadrons; Heavy Ions; In vitro testing; In vivo testing; In vivo tests; Inorganic Chemistry; Nuclear Chemistry; Nuclear Physics; Physical Chemistry; Proteins; Surgical implants; TCP (protocol); TCP; BSA; At; Stability; Conjugation
• ISSN: 0236-5731; 1588-2780
• DOI: 10.1007/s10967-010-0872-2

With 2,3,5,6-tetrafluorophenyl 3-( nodo -carboranyl) propionate (TCP) as a new potential bi-functional linker, bovine serum albumin (BSA) was conjugated with 211 At, and the conjugated model protein ( 211 At-TCP-BSA) was preliminarily evaluated in vitro and in vivo by comparison with 211 At-SAB-BSA and 211 At-SAPC-BSA, which conjugated with 211 At via aryl derivatives ATE ( N -succinimidyl-3-(tri- n -butylstannyl) benzoate) or SPC ( N -succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate). The radiolabeled intermediate 211 At-TCP was coupled to BSA in yields ranging from 35 to 45% with radiochemical purity of more than 98%. The conjugated 211 At-TCP-BSA exhibited considerable stability in vitro in 0.1 mol/L PBS (pH 7.6) at room temperature (RT), similar to 211 At-SAPC-BSA and 211 At-SAB-BSA. Biodistribution of the 211 At conjugated protein was investigated in NIH strain mice by I.V injection. The results showed that 211 At-TCP-BSA was constantly stable in vivo as well as in vitro, but more stable than 211 At-SAPC-BSA and 211 At-SAB-BSA. These results implied that radioastatinated carboranes based on B–At bonds are higher stability than radioastatinated aryl derivatives based on C–At to in vivo deastatination. In other word, TCP should be a promising bi-functional linker for 211 At conjugation of proteins or antibodies.