Labeling Polyamidoamine (PAMAM) Dendrimers with Technetium-99m via Hydrazinonicotinamide (HYNIC)

Abstract

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.

Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation

“…These NPs demonstrated significant liver, spleen and kidney uptake. 70 , 71 Similar distribution values have been reported for antibody-conjugated G4 dendrimer targeted to tumour antigens, with increased tumour uptake. 72 In comparison, smaller G2 particles possess a faster excretion rate.…”

Radiolabeling optimization and characterization of 68 Ga labeled DOTA–polyamido-amine dendrimer conjugate – Animal biodistribution and PET imaging results

“…However, radiolabeling of these conjugates as imaging probes has not been attempted so frequently. Recently, Kovacs et al (2014) have attempted to radiolabel PAMAM dendrimers with 99m Tc via hydrazinonicotinamide (HYNIC). These authors have reported the radiolabeling efficiency of 99.0% for 99m Tc–PAMAM–HYNIC conjugate and the preparation remained stable for up to 24-h.…”

Mannose receptor 1 expression does not determine the uptake of high-density mannose dendrimers by activated macrophages populations

“…In the present study, our goal was to develop an imaging agent that selectively targets TAMs that express MRC1. For this purpose, we used PAMAM G5 dendrimers, a class of macromolecules synthetic, highly branched, and monodisperse with well-defined size and shape [24,25]. They are formed of a multi-carbon ethylene diamine core and abundant numbers of the primary amino group on the surface, which allows doing a range of chemical modification to obtain specific biological properties.…”

“…They are formed of a multi-carbon ethylene diamine core and abundant numbers of the primary amino group on the surface, which allows doing a range of chemical modification to obtain specific biological properties. They are classified by generation number that is the number of focal points when going from the core towards the dendrimer surface [24]. PAMAM dendrimers have been widely used in biomedical applications in diagnosis and therapy [24][25][26][27][28][29][30][31][32][33].…”