PET/CT and MR imaging biomarker of lipid-rich plaques using [Cu-64]-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 50 mu l Cu-64-CD68-Fc (similar to 20-30 mu g labeled protein/mouse containing approximately 10-12MBq Cu-64-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 clinicalMR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23mm). Enhanced Cu-64-CD68-Fc uptake was found in the aortic arches of ApoE (/) compared to WT mice (ApoE (/) mice: 10.5 +/- 1.5Bq/cm(3) vs. WT mice: 2.1 +/- 0.3Bq/cm(3); 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 R-1 maps (R-1=1.47 +/- 0.06 s(-1) vs. 0.92 +/- 0.05 s(-1); P <0.001). Radiolabeled scavenger receptor (Cu-64-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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.