1005484-22-9Relevant academic research and scientific papers
Rational design and generation of a bimodal bifunctional ligand for antibody-targeted radiation cancer therapy
Chong, Hyun-Soon,Ma, Xiang,Le, Thien,Kwamena, Baidoo,Milenic, Diane E.,Brady, Erik D.,Song, Hyun A.,Brechbiel, Martin W.
, p. 118 - 125 (2008/09/18)
An antibody-targeted radiation therapy (radioimmunotherapy, RIT) employs a bifunctional ligand that can effectively hold a cytotoxic metal with clinically acceptable complexation kinetics and stability while being attached to a tumor-specific antibody. Clinical exploration of the therapeutic potential of RIT has been challenged by the absence of adequate ligand, a critical component for enhancing the efficacy of the cancer therapy. To address this deficiency, the bifunctional ligand C-NETA in a unique structural class possessing both a macrocyclic cavity and a flexible acyclic moiety was designed. The practical, reproducible, and readily scalable synthetic route to C-NETA was developed, and its potential as the chelator of 212Bi, 213Bi, and 177Lu for RIT was evaluated in vitro and in vivo. C-NETA rapidly binds both Lu(III) and Bi(III), and the respective metal complexes remain extremely stable in serum for 14 days. 177Lu-C-NETA and 205/6Bi-C-NETA possess an excellent or acceptable in vivo biodistribution profile.
