PET/CT and MR imaging biomarker of lipid-rich plaques using [64Cu]-labeled scavenger receptor (CD68-Fc)

Abstract

Continued uptake of modified low-density lipoproteins (LDL) by the scavenger receptor, CD68, of activated macrophages is a crucial process in the development of atherosclerotic plaques and leads to the formation of foam cells. Eight-weeks-old male Apolipoprotein E-deficient (ApoE-/-) mice (n=6) were fed a high-fat diet for 12 weeks. C57BL/6J wildtype (WT) mice served as controls (n=6). Positron emission tomography (PET) with an acquisition time of 1800s (NanoPET/CT scanner; Mediso, Hungary & Bioscan, USA) was carried out 24h after intravenous tail vein administration of 50µl 64Cu-CD68-Fc (~20-30µg labeled protein/mouse containing approximately 10-12MBq 64Cu-CD68-Fc per mouse). Three days after PET/CT, all mice received an intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-binding contrast agent to assess plaque burden and vessel wall remodeling. Two hours after injection, mice were imaged in a 3T clinical MR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23mm). Enhanced 64Cu-CD68-Fc uptake was found in the aortic arches of ApoE-/- compared to WT mice (ApoE-/- mice:10.5±1.5Bq/cm³ vs. WT mice: 2.1±0.3Bq/cm³; P=0.002). Higher gadolinium-based elastin-binding contrast agent uptake was also detected in the aortic arch of ApoE-/- compared to WT mice using R1 maps (R1=1.47±0.06 s-1 vs. 0.92±0.05 s-1; P <0.001). Radiolabeled scavenger receptor (64Cu-CD68-Fc) may help to target foam cell rich plaques with high content of oxidized LDL. This novel imaging biomarker tool may have potential to identify unstable plaques and for risk stratification.