Magnetic Resonance Angiography Using the Intravascular Contrast Agent Vasovist®

Magnetic Resonance Angiography Using the Intravascular Contrast Agent Vasovist®

Goyen Mathias
European Cardiovascular Disease 2006
Published: May 2006
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Atherosclerosis is a generalised disease and contributes to cardiac death, stroke, limb loss and a range of other illnesses. Disease in the major arteries, including the infra-renal abdominal aorta, internal iliac arteries, renal arteries and peripheral vasculature, remains a major cause of morbidity and mortality. For example, the prevalence of disease in the infra-renal abdominal aorta ranges from less than 3% in 60-year-old patients to 20% in 75-year-old patients 1,2, and the incidence increases with increasing age. Other forms of vascular disease such as renal artery stenosis present additional manifestations, including hypertension and renal failure. As the average age of the population increases, the burden of vascular disease is anticipated to increase.

Until recently, X-ray angiography (XRA) requiring arterial catheterisation and the use of substantial volumes of iodinated contrast agent was the clinical standard practice when a detailed image of the vasculature was required. However, less invasive imaging techniques using X-ray computed tomography (CT) or magnetic resonance imaging (MRI) have been developed. These imaging methods, either without exogenous contrast agents (MRI only) or with exogenous contrast agents (both CT and MRI) have become increasingly popular over the past few years as data have suggested that their accuracy, in some clinical settings, might approach that of the accepted standard diagnostic method, catheter XRA using iodinated dye. 3-5

Enhancement of MR images with exogenous contrast agents such as chelates of gadolinium or iron has become standard clinical practice in many settings. Such contrast agents provide technical benefits, including improved image quality, and clinical benefits, such as improved sensitivity and specificity for disease. Magnetic resonance angiography (MRA), a more recent development in MRI, uses tailored acquisition sequences to highlight blood flow and is widely used to assist in the management of patients with vascular diseases, especially in the brain. In many vascular beds like peripheral vessels, however, noncontrast MRA is not used routinely in clinical practice due to shortcomings of unenhanced MRA and/or the limitations of currently available MR contrast agents.

What is Vasovist ®?
MS-325 is the product development code for the drug product containing trisodium gadolinium (international non-proprietary name: gadofosveset) as the active substance. Vasovist® injection is composed of an aqueous solution (244mg/ml, 0.25mmol/litre) of drug substance, gadofosveset trisodium, and a small amount of ligand excipient, fosveset, to ensure minimal free gadolinium in solution. The drug substance consists of a stable gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) chelate substituted with a diphenylcyclohexylphosphate group. Vasovist® injection is a clear, colourless to slightly yellow solution in which the pH has been adjusted from 6.5 to 8.0. The density is 1.12g/ml and the osmolality ranges from 700–950mOsm/Kg at 37ºC. The viscosity of Vasovist® injection ranges from 2.7 to 3.3cps at 20ºC. The molecular formula is C33H40GdN3Na3O15P and the molecular weight for the anhydrous form is 957.86. Vasovist® is administered either by a hand or power injector to deliver a dose of 0.03mmol/kg in 25-30 seconds.

Overview of the Clinical Development Programme
Prior to approval in the EU, Vasovist® underwent extensive evaluation of the safety and efficacy of the drug. The clinical development programme for efficacy included two phase II studies and four phase III studies. In phase II studies, approximately 300 patients were evaluated to define optimal dose for MRA. The optimal dose for MRA was found to be 0.03mmol/kg. The clinical effectiveness of Vasovist® was demonstrated through analysis of efficacy data of 672 patients who were included in four adequate and wellcontrolled phase III studies. Vascular beds representative of areas of turbulent blood flow to an organ and slow flow were studied. In all of these studies, the fundamental methodology was the same.

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