Metal-Polymer Complexes of Gallium/Gallium-68 with Copolymers of N-Vinylpyrrolidonewith N-Vinylformamideand N-Vinyliminodiacetic Acid: A Hint for Radiolabeling of Water-Soluble Synthetic Flexible Chain Macromolecules.

Nikolay I Gorshkov,Аlexander V Tokarev,Аlbert I Kipper,Sergei V Shatik,Iirina I Gavrilova,Еvgenii F Panarin,Valerii D Krasikov,Мarina А Bezrukova,Аndrey Yu Murko

doi:10.3390/polym12122889

Abstract

Copolymer of N-vinylpyrrolidone (VP) with vinylformamide (VFA) and N-vinyliminodiacetic acid (VIDA) was synthesized; its metal-polymer complexes (MPCs) with gallium were obtained. The complexes were characterized by size exclusion chromatography, hydrodynamic and optical methods, scanning electron microscopy, and spectral methods (UV, IR, 1Н NMR spectroscopy). It was demonstrated that in going from polymer to complex, hydrodynamic parameters of macromolecules change only slightly, although the polymer contains intramolecular Ga(VIDA)2 fragments in its structure. A new method for preparation of MPCs with gallium and gallium-68 radionuclide was suggested. The obtained metal-polymer complex is stable over a wide range of pH values as well as in the histidine challenge reaction. In vivo distribution experiments in intact animals showed high primary accumulation of thegallium-68 MPC in blood with subsequent excretion via urinary tract.

Highlights

Nuclear medicine is a modern non-invasive method for diagnostics and therapy of various pathologies, including oncological diseases
The goals of the present work included the synthesis of N-vinylpyrrolidone(VP)/N-vinylformamide (VFA) copolymers containing N-vinyliminodiacetic acid (VIDA) as a bifunctional chelating agent (VP-VFA-VIDA), characterization of the copolymers by spectroscopic and chromatographic methods, study of complexation between the copolymer and gallium ion, isolation of metal-polymer complexes (MPC) (VP-VFA-VIDA)-Ga, estimation of their stability at various pH values and in histidine challenge reaction (HCR), determining conditions of radiochemical synthesis, and evaluation of biological distribution of radiolabeled MPC in intact laboratory animals
Introducing metal ions into flexible chain polymer carriers is a rather complex task, since coordination properties of polymers depend on (a) molecular mass, polydispersity and structural parameters of polymers; (b) polyelectrolyte effects that exert an influence of conformational behavior of polymers in solutions; and (c) steric availability of coordination groups of bifunctional chelating agents (BFC) [20]