Nucl Med Mol Imaging.  2010 Sep;44(3):185-192.

A New Synthesis of TE2A-a Potential Bifunctional Chelator for (64)Cu

• Pandya DN
• Kim JY
• Kwak W
• Park JC
• Gawande MB
• An GI
• Ryu EK
• Yoo J

Abstract

PURPOSE
The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of disease-specific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator.
METHODS
TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with (64)Cu and microPET imaging was performed to follow the clearance pattern of the (64)Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with (64)Cu.
RESULTS
TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that (64)Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with (64)Cu in 94% yield within 30 min.
CONCLUSION
TE2A can be used by itself as a bifunctional chelator without any further structural modification.

Keyword

TE2A; Bifunctional chelator; (64)Cu; Conjugation; RGD peptide

MeSH Terms

Acetates
Alkylation
Heterocyclic Compounds
Kidney
Liver
Oligopeptides
Peptides, Cyclic
Acetates
Heterocyclic Compounds
Oligopeptides
Peptides, Cyclic