Local delivery of CER-001 in advanced plaques
Proof-of-concept for apoA-1 as initiator of reverse cholesterol transport

Atherosclerosis is considered a chronic inflammatory disease in which macrophages play a major role by taking up (oxidized) low-density lipoprotein (LDL). The lipid-laden macrophages accumulate and undergo apoptosis leading to the formation of a necrotic core and eventually the vulnerable plaque. Cholesterol efflux from lipid-laden macrophages is a key atheroprotective mechanism, a process referred to as reverse cholesterol transport (RCT) in which apolipoprotein (apo)A-1 and HDL particles remove cholesterol from peripheral cells. In view of the abundant evidence for apoA-1 on stimulating efflux from macrophages in vitro, it is reasonable to assume that apoA-1 will also stimulate efflux from vessel wall macrophages in vivo if apoA-1 succeeds in getting into the proximity of plaque macrophages. The radio-isotope Zirconium-89 (89Zr) has emerged as a ‘gold-standard’ in the field of antibody-based PET imaging. The experience in oncology and the fact that 89Zr-labeling is a GMP-approved method makes this a suitable candidate for proving target delivery of apoA-1/HDL into advanced atherosclerotic plaques in humans using non-invasive imaging techniques. With this project we aim to show that exogenously infused apoA-1 (CER-001®) penetrates into advanced plaques in patients, making it ‘highly likely’ that efflux of cholesterol from macrophages to the apoA-1/HDL complex will occur.

To demonstrate that 89Zr-CER-001 penetrates into atherosclerotic plaques in patients by means of PET imaging.

PET/CT scans will be performed at timepoints 10 minutes, 24 hours and 72 hours after 89Zr-CER-001 infusion.

Infusion with (89Zr-)CER-001 and PET-CT imaging