Abstract 5765: 3T MRI Molecular Imaging of Benfluorex Treatment of Metabolic Syndrome with αvβ3-Integrin Targeted Nanoparticles
1.5T MRI with αvβ3-integrin targeted gadolinium nanoparticle contrast agents (NP) can detect stage I atherosclerosis in experimental animals by localizing specifically to inflammatory plaque components within minutes after injection. We hypothesized that NP could serve as an early surrogate biomarker of therapeutic efficacy for benfluorex treatment of metabolic syndrome in diabetic JCR-LA:cp rats on a 3T clinical scanner. Six week old JCR-LA:cp rats (n=6) received benfluorex in their feed (0.069% wt/wt) for 16 weeks, while control animals (n=5) received regular diet. The abdominal aorta was imaged (T1w spin echo) in 4 cross-sections at baseline and 2-hour post-injection (IV, 1.0 ml/kg NP) every 4 wks with a 3.0 T whole-body clinical MRI scanner, and total aortic wall signal was computed across all sections. Treatment of diabetic JCR-LA:cp rats with benfluorex reduced food consumption and body weight (16.0%; p<0.05); and fasting plasma insulin, leptin and triglyceride were decreased by 52.6%, 18.2% and 36.2% in treated animals. Aortic wall signal for untreated animals rose progressively, whereas signal in treated animals progressively decreased, indicative of attenuation of angiogenesis and vascular inflammation (Figure⇓, *p<0.05). These observations represent the first report of the use of molecular imaging with an MRI surrogate biomarker at clinical field strength for quantifying therapeutic efficacy in a model of metabolic syndrome.
This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).