Premium
Convenient Synthesis and Evaluation of a Heptadentate Bifunctional Ligand for Radioimmunotherapy Applications
Author(s) -
Chong HyunSoon,
Sun Xiang,
Dong Pengfei,
Kang Chi Soo
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101063
Subject(s) - chemistry , radioimmunotherapy , conjugate , bifunctional , chelation , conjugated system , combinatorial chemistry , ligand (biochemistry) , stereochemistry , kinetics , aziridine , ring (chemistry) , antibody , monoclonal antibody , organic chemistry , catalysis , biochemistry , receptor , polymer , mathematical analysis , mathematics , physics , quantum mechanics , immunology , biology
An efficient synthetic route to a bifunctional chelating agent C ‐NE3TA‐NCS for antibody‐targeted radioimmunotherapy (RIT) applications was developed. Various synthetic methods centered on key reaction steps, including bimolecular cyclization, ring‐opening reactions of aziridine and aziridinium cations, and reductive amination, were explored to optimize the preparation of a tetraaza‐based chelate TANPA and C ‐NE3TA analogues. Heptadentate C ‐NE3TA‐NCS was conjugated to a tumor‐targeting antibody and compared with hexadentate C ‐NOTA‐NCS for radiolabeling reaction kinetics with lanthanides for RIT. The C ‐NE3TA–antibody conjugate displayed significantly enhanced complexation kinetics with 90 Y compared with the C ‐NOTA–antibody conjugate. The synthetic methods for TANPA and C ‐NE3TA‐NCS reported herein have broad applications for the preparation of bifunctional and macrocyclic chelating agents.