Simvastatin

Simvastatin was purchased from Cayman Chemical (Ann Arbor, MI). Simvastatin was activated prior to its use as previously described (Borahay et al., 2015 ). Activation converts the prodrug (lactone structure) to its active form (β-hydroxyacid structure). Briefly, Simvastatin (25 mg) was dissolved in 625μL of ethanol. This solution was then added to 935μL of 0.1 NaOH and heated in a water bath (50°C) for 2 hours before diluting with water. The pH was adjusted to reach 7 using HCl. This solution was diluted 8-fold with water to reach a 2mg/mL concentration and was sterile filtered before being stored at 4°C until use.
Simvastatin-loaded liposome nanoparticles (Simvastatin-NP) was prepared using 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC) which were purchased from Avanti Polar Lipids (Alabaster, AL) and 1,2-Distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE). DOPC/DSPE-Peg2000 were prepared in 10:1 mixture and Simvastatin-DOPC/DSPE-Peg2000 was prepared in 1:10 mixture. Simvastatin-DOPC/DSPE-Peg2000 was kept lyophilized at −20°C and dissolved in normal saline immediately prior to use.

Phospholipids (DMPC, MHPC and DSPE) and simvastatin were purchased from Avanti Polar Lipids (Alabaster, AL) and AK Scientific (Union City, CA), respectively. All other chemicals were acquired from Sigma-Aldrich (St. Louis, MO). APOA1 was isolated from human HDL concentrates (Bioresource Technology, Weston, FL) following a previously described procedure (17 (link)). ⁸⁹Zr was produced at Memorial Sloan-Kettering Cancer Center on an EBCO TR19/9 variable-beam energy cyclotron (Ebco Industries Inc., Vancouver, BC, Canada) via the ⁸⁹Y(p,n)⁸⁹Zr reaction and purified in accordance with previously reported methods(18 (link)). ¹⁸F was produced via the¹⁸O(p,n)¹⁸F reaction using a GEMS PETtrace-800 cyclotron (GE Healthcare, Chicago, IL).