The loading of gallium-68 into polymersomes

Abstract

A polymersome is a type of nanocarrier made of amphiphilic block copolymers, consisting of a hydrophobic bilayer, a hydrophilic brush-like outer shell and a hollow, aqueous core, which is formed through self-assembly. Polymersomes could be useful in the treatment of cancer as carrier to deliver and release drugs or radionuclides to tumours locally to reduce them without damaging healthy tissue. For this purpose, it could rely on the Enhanced Permeation and Retention (EPR) effect to accumulate in tumours, which requires a long blood circulation time. Reports have shown that while the circulation half-life in healthy mice is in the order of hours, it decreases to the order of minutes in diseased mice, preventing any uptake of polymersomes in tumours. So, more research needs to be done on the in vivo biodistribution for each type of polymersome to assess whether it is suitable for radiotherapy. Thus far, imaging for polymersome in vivo biodistribution mostly relies on the use of In-111 and Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) as imaging technique. In this report it is researched whether it is possible to load gallium-68 (positron emitter, half-life 67.71 min) into poly(1,2-butadiene)-b-poly(ethylene oxide) {PBd(1800 g mol^-1)-b-PEO(600 g mol^-1)} polymersomes using an active loading method, which has not been done so far. This would allow short-term imaging using Positron Emission Tomography (PET) as an alternative imaging technique. PET has a much higher sensitivity than SPECT, which allows better image quality or shorter scan times. These advantages make PET better than SPECT for clinical use.Using Ga-68 as the positron emitting source has the advantage on being able to rely on a germanium-68/gallium-68 generator to produce Ga-68 on-site and being independent of external radionuclide suppliers.In this report the pH dependency of the formation of complex of Ga-68 with a lipophilic ligand was researched, the transfer of Ga-68 from the lipophilic ligand to a hydrophilic chelator was optimised, and loading experiments of Ga-68 into polymersomes were conducted. It was demonstrated that it is indeed possible to load Ga-68 into polymersomes, and maximum loading efficiencies of up to 36% were found. It is argued that the low loading efficiency could be caused by an unexpectedly thick hydrophobic bilayer of the prepared polymersomes, and possibly by a low amount of encapsulated hydrophilic chelator compared to the applied amount of lipophilic ligand. But more research needs to be done to confirm these observations.