Synthesis, conjugation, and radiolabeling of a novel bifunctional chelating agent for 225Ac radioimmunotherapy applications

Lara L. Chappell, Kim A. Deal, Ekaterina Dadachova, Martin W. Brechbiel

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


225Ac (t(1/2) = 10 days) is an alternative α-emitter that has been proposed for radioimmunotherapy (RIT) due to its many favorable properties, such as half-life and mode of decay. The factor limiting use of 225Ac in RIT is the lack of an acceptably stable chelate for in vivo applications. Herein is described the first reported bifunctional chelate for 225Ac that has been evaluated for stability for in vivo applications. The detailed synthesis of a bifunctional chelating agent 2-(4-isothiocyanatobenzyl)-1,4,7,10,13,16-hexaazacyclohexadecane- 1,4,7,10,13,16-hexaacetic acid (HEHA-NCS) is reported. This ligand was conjugated to three monoclonal antibodies, CC49, T101, and BL-3 with chelate-to-protein ratios between 1.4 and 2. The three conjugates were radiolabeled with 225Ac, and serum stability study of the [225Ac]-BL-3-HEHA conjugate was performed.

Original languageEnglish (US)
Pages (from-to)510-519
Number of pages10
JournalBioconjugate Chemistry
Issue number4
StatePublished - Jul 2000

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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