Nanoparticle applications in medicine have seen a tremendous growth in the last decade. In addition to their drug targeting application and their ability to improve bioavailability of drugs, nanoparticles can be designed to allow their detection with a variety of imaging methodologies. In the current study we developed a multimodal nanoparticle platform to enable imaging guided therapy, which was evaluated in a colon cancer mouse model. This “theranostic” platform, is based on oil-in-water nanoemulsions and carries iron oxide nanocrystals for MRI, the fluorescent dye Cy7 for NIRF imaging and the hydrophobic glucocorticoid prednisolone acetate valerate (PAV) for therapeutic purposes. Angiogenesis targeted nanoemulsions functionalized with αvβ3-specific RGD-peptides were evaluated as well. When subcutaneous tumor were palpable the nanoemulsions were administered at a dose of 30 mg FeO/kg and 10 mg PAV/kg. MRI and NIRF imaging showed significant nanoparticle accumulation in the tumors, while tumor growth profiles revealed a potent inhibitory effect in all the PAV-nanoemulsions treated animals as compared to the ones treated with control nanoemulsions, the free drug or saline. In conclusion, this study demonstrated that our nanoemulsions, when loaded with PAV, iron oxide nanocrystals and Cy7, represent a flexible and unique theranostic nanoparticle platform that can be applied for imaging guided therapy of cancer.

In this article, we present a first-pass perfusion imaging protocol to determine quantitative regional perfusion values (in mL min(-1) g(-1)) of the mouse myocardium. Perfusion was quantified using a Fermi-constrained deconvolution of the myocardial tissue response with the arterial input function. A dual-bolus approach was implemented. Experimental evidence is presented for the linearity of signal intensity in the left-ventricular lumen during the prebolus (r=0.99, P<0.001) and in the myocardium during the full-bolus injection (r=0.99, P<0.01) as function of Gd(DTPA)2- injection concentration used. The prebolus was used to reconstruct a nonsaturated arterial input function. Regional perfusion values proved repeatable in a cohort of nine healthy C57BL/6 mice. The perfusion values over two measurements with a 1-week interval were 7.3±0.9 and 7.2±0.6 mL min(-1) g(-1), respectively. No effects of time (P>0.05) and myocardial region (P>0.05) were observed. The between-session coefficient of variation was only 6%, whereas the inter-animal coefficient of variation was 11 and 8% for the separate experiments. We expect that the first-pass perfusion method here presented will be useful in preclinical studies of myocardial perfusion deficits and valuable to assess the impact of pro-angiogenic therapy after myocardial infarction.

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failure by transverse aortic constriction (TAC), which was not done thus far. Regional left ventricular (LV) myocardial perfusion (mL/min/g) was assessed in healthy mice (n = 6) and mice with TAC (n = 14). A dual-bolus first-pass perfusion MRI technique was employed to longitudinally quantify myocardial perfusion values between 1 and 10 weeks after surgery. LV function and morphology were quantified from cinematographic MRI. Myocardial rest perfusion values in both groups did not change significantly over time, in line with the essentially constant global LV function and mass. Myocardial perfusion was significantly decreased in TAC mice (4.2 ± 0.9 mL/min/g) in comparison to controls (7.6 ± 1.8 mL/min/g) (P = 0.001). No regional differences in perfusion were observed within the LV wall. Importantly, increased LV volumes and mass, and decreased ejection fraction correlated with decreased myocardial perfusion (P < 0.001, in all cases). Total LV blood flow was decreased in TAC mice (0.5 ± 0.1 mL/min, P < 0.001) in comparison to control mice (0.7 ± 0.2 mL/min). Myocardial perfusion in TAC mice was significantly reduced as compared to healthy controls. Perfusion was proportional to LV volume and mass, and related to decreased LV ejection fraction. Furthermore, this study demonstrates the potential of quantitative first-pass contrast-enhanced MRI for the study of perfusion deficits in the diseased mouse heart.