Abstract
1943
Objectives To develop versatile cage-like bifunctional chelators with high in vivo stability based on sarcophagine cages for Cu-64 radiopharmaceuticals.
Methods A novel sarcophagine caged-like bifunctional chelator, named AmBaSar, was developed. The new chelator containing a hexa-aza cage for Cu-64 radiolabeling and a linker aromatic carboxyl for peptide conjugation was designed and prepared using a conventional synthetic strategy, and characterized by elemental analysis, MS and 1H-NMR. The bifunctional chelator was conjugated with the cyclic peptide RGD, and then labeled with Cu-64 as a prototype agent.
Results The AmBaSar was labeled with Cu-64 in pH 5.0 ammonium acetate buffer solution with radiochemical yield ≥ 95% after 60 min incubation on 37 °C. The AmBaSar conjugated cyclic peptide RGD was prepared in 80% yield. Labeling with Cu-64 provided final product in 80% radiochemical yield and 95% radiochemical purity after 60 min. Preliminary biological evaluation of this new Cu-64-chelator in normal mouse demonstrates renal clearance as the primarily mode of excretion.
Conclusions The novel versatile sarcophagine caged-like bifunctional chelator AmBaSar was designed, synthesized, and characterized. The new chelator AmBaSar was conjugated with the cyclic peptide RGD, and then labeled with Cu-64 to form the new PET probe Cu-64 AmBaSar-RGD for imaging the ανβ3 integrin receptor.
- © 2009 by Society of Nuclear Medicine