Labeling polyamidoamine (PAMAM) dendrimers with technetium-99m via hydrazinonicotinamide (HYNIC)

Dendrimers are branched nanomolecules, with a three dimensional structure, very low polydispersity and high functionality. Poly(amidoamine) (PAMAM) dendrimers are the most investigated class of dendrimers. In this study, PAMAM G4 dendrimer conjugated with HYNIC (hydrazinonicotinamide), an efficient bifunctional chelator, was characterized. Structure of the derivatized dendrimer was confirmed by (1)H-NMR and (13)C-NMR spectra and MALDI-TOF mass spectrometry. HYNIC-dendrimer was labeled with technetium-99m testing three different co-ligands (tricine, nicotinic acid and ethylenediaminodiacetic acid). The radiolabeled complexes were characterized by reverse phase HPLC, as well as their stabilities. Radiolabeling yield was about 99% with all co-ligands and complexes were found stable for 24 h. Biodistribution studies were performed administrating tricine-(99m)Tc-HYNIC-dendrimer, nicotinic acid-(99m)Tc-HYNICdendrimer and EDDA-(99m)Tc-HYNIC-dendrimer to normal mice; results showed blood clearance with hepatic and renal depuration in all cases. In this sense, labeling of PAMAM G4 dendrimer with technetium-99m using HYNIC could be obtained in high yield in a simple method and with high specific activity.