Structural Effects on the Biodistribution and Positron Emission Tomography (PET) Imaging of Well-Defined ⁶⁴Cu-Labeled Nanoparticles Comprised of Amphiphilic Block Graft Copolymers

Abstract

The synthesis of poly(methyl methacrylate-co-methacryloxysuccinimide-graft-poly(ethylene glycol)) (PMMA-co-PMASI-g-PEG) via living free radical polymerization provides a convenient route to well-defined amphiphilic graft copolymers having a controllable number of reactive functional groups, variable length PEG grafts, and low polydispersity. These copolymers were shown to form PMMA-core/PEG-shell nanoparticles upon hydrophobic collapse in water, with the hydrodynamic size being defined by the molecular weight of the backbone and the PEG grafts. Functionalization of these polymeric nanoparticles with a 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) ligand capable of chelating radioactive 64Cu nuclei enabled the biodistribution and in vivo positron emission tomography of these materials to be studied and directly correlated to the initial structure. Results indicate that nanoparticles with increasing PEG chain lengths show increased blood circulation and low accumulation in excretory organs, suggesting the possible use of these materials as stealth carriers for medical imaging and systemic administration.

PEGylated polymers for medicine: from conjugation to self-assembled systems

“…Examples of micelles with cross-links in the corona are referred to as shell cross-linked micelles (SCMs), or shell cross-linked nanoparticles (termed SCKs, after the initially-coined term ''shell cross-linked knedels''). Wooley and co-workers described the preparation and characterization of SCKs in 1996, 141 and the concept has since been extended considerably to provide a suite of tailored nanoparticles for drug delivery, 142 by the addition of biologically active moieties, [143][144][145][146][147] imaging agents, 148,149 stimuli-sensitive and degradable linkages, 11,13,150,151 core excavation, 16 and PEGylation. 152 One recent detailed study compared PEGylated and non-PEGylated SCK's with different hydrophobic cores, one consisting of the malleable poly(methyl acrylate), and the other composed of hard polystyrene.…”

The cell labeling efficacy, cytotoxicity and relaxivity of copper-activated MRI/PET imaging contrast agents

“…DOTA is a well-established ligand to form stable complex with metal ions like Cu(II), Gd(III) and In(II) [47]. DOTA derived ligands have widely been utilized to coordinate radioactive metal ions to use as PET imaging agent [48]. For the controlled incorporation of 64 Cu, highly efficient Cu(II) binding ligand, DOTA was chosen.…”

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

“…Biodistribution studies with polymersomes, in particular, would be greatly aided by the encapsulation of an imaging agent in the vesicles; this would enable non-invasive monitoring of the location of vesicles during drug delivery without the need to sacrifice the animal. Although nanoparticles have been used with a spectrum of different imaging modalities including PET [48,49] and MRI [50][51][52], here we will focus on polymersomes that encapsulate fluorescent agents for optical imaging. Because light scattering decreases with increasing wavelength, and hemoglobin and water absorption spectra have their nadir in the near infrared (NIR) spectral region, much work has been focused on developing NIR contrast agents for in vivo imaging studies [9].…”