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The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m ( 99m Tc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of 99m Tc, 5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V 2 DTPA) for labeling of Gd, and vinylbenzyl-O-β-d-galactopyranosyl-d-gluconamide (VLA) for targeting ASGPR were synthesized, respectively. Then the copolymer P(VLA-co-VNI-co-V 2 DTPA) (pVLND 2 ) was synthesized and characterized by gel permeation chromatography, dynamic light scattering, and high-performance liquid chromatography analysis. After labeling with 99m Tc and Gd simultaneously, the radiochemical purity, toxicity, relaxivity (r 1 ), and in vivo SPECT/MR imaging in mice were evaluated. Single-photon emission computed tomography/magnetic resonance imaging and biodistribution results showed that pVLND 2 could target ASGPR well. The significantly improved signal to noise ratio was observed in mice liver during MR imaging. All the results suggest that this novel kind of copolymer has the potential to be further developed as a functional SPECT/MR imaging agent.

A Novel Copolymer-Based Functional SPECT/MR Imaging Agent for Asialoglycoprotein Receptor Targeting