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

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.

Introduction of Re(CO)3+/99mTc(CO)3+ Organometallic Species into Vinylpyrrolidone-Allyliminodiacetate Copolymers

“…As can be seen, no significant changes in MWD between starting co-polymers and resulting MPCs were observed. The same tendency was observed previously [ 33 , 34 ] using more precise methods, e.g., molecular hydrodynamics and optics in combination with SEC. This fact suggests the hypothesis, that the introduction of metals into the macromolecular matrix will not significantly disturb its hydrodynamical and biological properties and, thus, should not drastically disturb its biological behavior.…”

“…The same effect occurring in 1 H NMR spectra of similar metal–polymer complexes Ga-VP-VIDA has been previously described [ 27 ]. The coupling of signals of methylene protons was also observed in 1 H NMR spectra of low molecular weight complex [Re(CO) 3 (IDA)][N(Et) 4 ] [ 34 ].…”

“…Therefore, firstly, we studied the possibility of complexation between Re(CO) 3 + organometallic compound and PVP (MM = 30 kDa) by HPLC on ultrashort monolith columns (carboxymethyl modification). The use of monolithic sorbents, which are able to separate both homopolymers in a gradient mode and metal ions [ 33 , 34 ], may be a possible solution of a complex problem of separation of flexible-chain BASP and metal ions.…”

“…The reaction between polymer amino groups and monochloroacetic acid was carried out in KOH water solution (pH = 10) at 90 °C [ 34 , 36 ]. The content of IDA-containing groups was estimated by potentiometric titration.…”

“…Previously, we have reported the introduction of the iminodiacetate (IDA) chelation unit into vinylpyrrolidone–vinylformamide copolymers; complexation of this macromolecular chelator with group (III) metals (gallium, indium) and the corresponding radionuclides ( 68 Ga, 111,113 In) has been investigated [ 33 , 34 ]. Iminodiacetate is also known as a powerful ligand for linking M(CO) 3 + species in aqueous solutions [ 28 ].…”