Preclinical Studies of MVT-100, A Novel Ultrasound Enhancing Agent

Over the past decades, many investigations have used perfluorocarbon (PFC)-based contrast products to enhance ultrasound (US) imaging. Currently octafluoropropane (OFP), decafluorobutane, and sulfur hexafluoride or a combination of those gases is used for the preparation of ultrasound enhancing agents (UEA). This study reports the development of MVT-100, a novel microbubble ultrasound enhancing agent (UEA) designed for improved stability, safety, and imaging performance. The objective of these studies was to fully characterize and compare the biophysical, chemical and in vivo properties of the new UEA (herein referred to as MVT-100) as compared with the well-known and widely utilized UEA known as perflutren lipid microspheres (Perflutren) (commercialized under the name of Definity®).

Analytical methods were used to characterize the MBs. Low mechanical index (MI) contrast-enhanced ultrasound was performed in mice and pigs.

Comparison of Perflutren MB with MVT-100 MB showed similarities of the products in their overall particle numbers, gas content, osmolality, pH and phospholipid concentrations. However, MVT-100 exhibited a zeta potential that was essentially neutral (+0.5 ± 0.1 mV), compared with the negative zeta potential of Perflutren (-4.2 ± 2.0 mV), a tighter size distribution and lower polydispersity index (0.114 ± 0.012 vs. 0.159 ± 0.036, p = 0.048). Under accelerated storage conditions (40°C for 4 weeks), MVT-100 demonstrated markedly greater lipid stability, with only 2.05% loss of total phospholipid content compared with 13.10% for Perflutren. Murine renal retention studies showed that MVT-100 MB exhibited significantly lower (∼2.5 fold) renal retention in the kidney as compared with Perflutren. In porcine studies, MVT-100 hemodynamic parameters were identical to those of Perflutren. Echocardiographic porcine studies showed that ventricular opacification and endocardial border delineation following MVT-100 administration were comparable between agents at early time points, with higher and more sustained opacification with MVT-100 at later time points (generalized linear mixed model: main effect of agent p < 0.001, time × agent interaction p < 0.001) and no evidence of a significant difference in acoustic shadowing between agents (p > 0.99).

MVT-100 is a novel UEA that exhibits promising properties as a new imaging agent for contrast echocardiography with appealing storage conditions.