HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Synthesis and preclinical evaluation of bifunctional ligands for improved chelation chemistry of 90Y and 177Lu for targeted radioimmunotherapy.

Abstract
We report a practical and high-yield synthesis of a bimodal bifunctional ligand 3p-C-NETA-NCS containing the isothiocyanate group for conjugation to a tumor targeting antibody. 3p-C-NETA-NCS was conjugated to a tumor-targeting antibody, trastuzumab, and the corresponding 3p-C-NETA-trastuzumab conjugate was evaluated and compared to trastuzumab conjugates of the known bifunctional ligands C-DOTA, C-DTPA, and 3p-C-DEPA for radiolabeling kinetics with (90)Y and (177)Lu. 3p-C-NETA-trastuzumab conjugate exhibited extremely rapid complexation kinetics with (90)Y and (177)Lu. (90)Y-3p-C-NETA-trastuzumab and (177)Lu-3p-C-NETA-trastuzumab conjugates were stable in human serum for 2 weeks. A pilot biodistribution study was conducted to evaluate in vivo stability and tumor targeting of (177)Lu-radiolabeled trastuzumab conjugate using nude mice bearing ZR-75-1 human breast cancer. (177)Lu-3p-C-NETA-trastuzumab conjugate displayed low radioactivity level at blood (1.6%), low organ uptake (<2.2%), and high tumor-to-blood ratio (6.4) at 120 h. 3p-C-NETA possesses favorable in vitro and in vivo profiles and is an excellent bifunctional chelator that can be used for targeted RIT applications using (90)Y and (177)Lu and has the potential to replace DOTA and DTPA analogues in current clinical use.
AuthorsChi Soo Kang, Xiang Sun, Fang Jia, Hyun A Song, Yunwei Chen, Michael Lewis, Hyun-Soon Chong
JournalBioconjugate chemistry (Bioconjug Chem) Vol. 23 Issue 9 Pg. 1775-82 (Sep 19 2012) ISSN: 1520-4812 [Electronic] United States
PMID22881720 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Monoclonal, Humanized
  • Chelating Agents
  • Ligands
  • Yttrium Radioisotopes
  • Lutetium
  • Trastuzumab
Topics
  • Antibodies, Monoclonal, Humanized (chemistry)
  • Chelating Agents (chemistry)
  • Drug Evaluation, Preclinical
  • Kinetics
  • Ligands
  • Lutetium (chemistry)
  • Radioimmunotherapy
  • Trastuzumab
  • Yttrium Radioisotopes (chemistry)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: