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

摘要

Purpose The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of diseasespecific 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 Cu-64 and microPET imaging was performed to follow the clearance pattern of the 64CuTE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with Cu-64. Results TE2A was prepared in salt-free form from cyclam in an overall yield of 74. The microPET images showed that Cu-64-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 Cu-64 in 94 yield within 30 min. Conclusion TE2A can be used by itself as a bifunctional chelator without any further structural modification.