A palm oil-enriched diet induces dyslipidemia and ultrastructural alterations of endothelium with vascular smooth muscle cells migration in carotid artery

Abstract

Alpha-particle-emitting radionuclides have been the subject of considerable investigation as cancer therapeutics, since they have the advantages of high potency and specificity. Among α-emitting radionuclides that are medically relevant and currently available, the lead-212/bismuth-212 radionuclide pair could constitute an in vivo generator. Considering its short half-life (T1/2 = 60.6 min), 212Bi can only be delivered using labelled carrier molecules that would rapidly accumulate in the target tumor. To expand the range of applications, an interesting method is to use its longer half-life parent 212Pb (T1/2 = 10.6 h) that decays to 212Bi. The challenge consists in keeping 212Bi bound to the vector after the 212Pb decay. Preclinical and clinical studies have shown that a variety of vectors may be used to target alpha-emitting radionuclides to cancer cells. Nanoparticles, notably liposomes, allow combined targeting options, achieving high specific activities, easier combination of imaging and therapy and development of multimodality therapeutic agents (e.g., radionuclide therapy plus chemotherapy). The aim of this work consists in assessing the in vitro stability of 212Pb/212Bi encapsulation in the liposomes. Indeed, the release of the radionuclide from the carrier molecules might causes toxicity to normal tissues. To reach this goal, Asymmetrical Flow Field-Flow Fractionation (AF4) coupled with a Multi-Angle Light Scattering detector (MALS) was used and coupling with a gamma (γ) ray detector was developed. AF4-MALS-γ was shown to be a powerful tool for monitoring the liposome size together with the incorporation of the high energy alpha emitter. This was successfully extended to assess the stability of 212Bi-radiolabelled liposomes in serum showing that more than 85% of 212Pb/212Bi is retained after 24 h of incubation at 37 °C.