What is MRA?

MRA, or magnetic resonance angiography, is a form of magnetic resonance imaging (MRI) using magnetic field and pulse radio waves to image the arteries, blood vessels that carry blood to our organs and tissues. MRA has several advantages over other forms of angiography. Unlike X-ray methods (conventional X-ray angiography or CT angiography), it involves no ionizing radiation. In addition, unlike conventional angiography, it does not involve insertion of a catheter.¹

What is ABLAVAR^®?

ABLAVAR^® is the first and only contrast agent designed and FDA-approved specifically for use as a contrast agent in magnetic resonance angiography (MRA). ABLAVAR^® is indicated to evaluate aortoiliac occlusive disease (AIOD) in adults with known or suspected peripheral vascular disease.^2,3

ABLAVAR^® is a blood-pool contrast agent that reversibly binds to a protein in the blood called albumin.² This binding provides an expanded imaging window of up to 1 hour, which allows you to obtain bright, high-resolution, steady-state images in addition to finely detailed, first-pass images with a single dose that contains 70% less gadolinium than all other agents used in MRA.^*2,4-9

*Of these agents, only ABLAVAR^® is approved for MRA.

What is an MRA blood-pool contrast agent?

An MRA blood-pool contrast agent is specifically designed to stay in the intravascular space (blood pool) long enough to provide bright, finely detailed, steady-state and first-pass images, which can lead to better delineation of vessel pathology.⁹

How does ABLAVAR^® work?

Following intravenous injection, ABLAVAR^® binds reversibly to endogenous serum albumin resulting in longer vascular residence time than non-protein binding contrast agents, which provides the increased imaging window.^2,9,10 The binding to serum albumin also increases the magnetic resonance relaxivity of ABLAVAR^® and decreases the relaxation time (T1) of water protons resulting in an increase in signal intensity (brightness) of blood.²

What are the results and benefits of the albumin binding of ABLAVAR^®?

Results of albumin binding	Practical benefit
Long vascular (blood pool) residence time2,9	Allows up to 1 hour (when needed) to image vascular tree2,9 Allows for steady-state MRA with increased spatial resolution and without the need for bolus timing2,9
Increased magnetic resonance relaxivity2,9,11	Lowers the dose needed2,12 Increases spatial resolution9 Decreases need for repeat dosing9,11 Increases signal intensity of blood2

Are there any advantages to using ABLAVAR^® for first-pass imaging?

Yes. Because ABLAVAR^® has high relaxivity, it provides a bright bolus for first-pass imaging at a dose of gadolinium that contains 70% less gadolinium than the dose typically used for MRA.^*2,4-8,13

*Of these agents, only ABLAVAR^® is approved for MRA.

What are the advantages of steady-state imaging?

Images can be acquired for up to 1 hour after injection when needed.^9,2 Steady-state images can be acquired with high spatial resolution, providing increased accuracy in depiction of vessels and visualization of vessel walls.⁹ The accuracy and diagnostic confidence of CE-MRA are enhanced by steady-state studies, and patient management can be impacted.^14-16 Steady-state images may also be useful when the first-pass bolus is missed, when patient movement blurs the images, or when more detail is required to reexamine diseased vasculature noted on first-pass images.^17,18

Further demonstration of the benefits of steady-state imaging can be found in a 2008 article by Hadizadeh et al in Radiology.¹⁸

How did ABLAVAR^® perform in clinical trials?

In both pivotal clinical trials, ABLAVAR^® demonstrated accuracy that was comparable to conventional X-ray angiography with fewer uninterpretable studies than both 2-D time-of-flight and conventional angiography.^14,15

Has ABLAVAR^® been used elsewhere in the world?

Yes, the same contrast agent, gadofosveset trisodium, has been in use in the EU and Canada, and some other countries, since 2005.¹⁹

What is the safety profile of ABLAVAR^®?

In clinical trials and postmarket experience, the safety profile of ABLAVAR^® has been similar to that of other gadolinium-based MR contrast agents.^13,14

Side effects were generally mild and transient.^14,15 The most common adverse events reported in patients receiving the label dose of 0.03 mmol/kg were itching of the skin, also called pruritis (5%), headache (4%), and nausea (4%).² Anaphylactoid/anaphylactic reactions occurred in 0.1% (2/1676) of patients during clinical trials.²

How is ABLAVAR^® excreted?

ABLAVAR^® is eliminated primarily in the urine, with between 79% and 94% (mean of 83.7%) of an injected dose recovered in the urine. Of the total ABLAVAR^® recovered in urine, 94% is recovered within the first 72 hours. A small portion of ABLAVAR^® dose is recovered in feces (approximately 4.7%).²

Are there any known drug interactions with ABLAVAR^®?

No drug interaction reactions were observed in clinical trials. Consider the possibility of ABLAVAR^® interaction with concomitantly administered medications that bind to albumin. In a trial of 10 patients taking a stable dose of warfarin, a single dose of ABLAVAR^® did not alter the anticoagulant activity of warfarin as measured by the INR.²

What is the recommended dose of ABLAVAR^®?

The recommended dose is 0.03 mmol/kg (0.12 mL/kg), a dose unique among all Gd agents used in MR imaging because it contains 70% less Gd in 40% less volume than these other agents.*^2,4-8 Administer ABLAVAR^® as an intravenous bolus injection, manually or by power injection, over a period of time up to 30 seconds followed by a 25-30 mL normal saline flush.²

*Of these agents, only ABLAVAR^® is approved for MRA.

What are the recommended imaging guidelines?

ABLAVAR^® imaging is completed in 2 stages: the first-pass (dynamic) imaging stage and the steady-state (equilibrium) imaging stage. Both stages are essential for adequate evaluation of the arterial system, and dynamic imaging always precedes steady-state imaging. During interpretation of the steady-state images, ABLAVAR^® within the venous system may limit or confound the detection of arterial lesions.²

To assess the initial distribution of ABLAVAR^® within the arterial system, begin dynamic imaging immediately upon injection. Begin steady-state imaging after dynamic imaging has been completed, generally 5 to 7 minutes following ABLAVAR^® administration. At this time point, ABLAVAR^® is generally distributed throughout the blood. In clinical trials, steady-state imaging was completed within approximately 1 hour following ABLAVAR^® injection.²

Does ABLAVAR^® require a power injector for administration?

No, the ABLAVAR^® bolus may be administered either manually or by power injector.²

Can the vial be used again once opened?

ABLAVAR^® is intended for single-use only and should be used immediately upon opening. Discard any unused portion of the ABLAVAR^® vial.²

Are MRA contrast agents reimbursed by private insurance or Medicare?

Reimbursement policies vary from insurer to insurer, and you will need to check in each case. Lantheus Medical Imaging, Inc. provides basic ABLAVAR^® reimbursement information for healthcare professionals on the reimbursement page of this web site. Reimbursement information is also available through the Reimbursement Support Line: (800) 362-2668 ext. 7995. However, Lantheus Medical Imaging, Inc. cannot guarantee that use of any information provided will result in coverage or payment at any particular level.

Lantheus Medical Imaging, a worldwide leader in diagnostic medicine for more than 50 years, is dedicated to creating and providing pioneering medical imaging solutions to improve the treatment of human disease.  The company’s proven success in discovering, developing and marketing innovative medical imaging agents provides a strong platform from which to bring forward new breakthrough tools for the diagnosis and management of disease.  Lantheus imaging products include the echocardiography contrast agent DEFINITY® Vial for (Perflutren Lipid Microsphere) Injectable Suspension; ABLAVAR® (gadofosveset trisodium), a first-in-class magnetic resonance agent indicated for the evaluation of aortoiliac occlusive disease in adults with known or suspected peripheral vascular disease; TechneLite® (Technetium Tc99m Generator); Cardiolite® (Kit for the Preparation of Technetium Tc99m Sestamibi for Injection); and Thallium 201 (Thallous Chloride Tl 201 Injection).  Lantheus has more than 650 employees worldwide with headquarters in North Billerica, Massachusetts, and offices in Puerto Rico, Canada and Australia.  For more information, visit www.lantheus.com.

Please see full Prescribing Information, including boxed WARNING regarding Nephrogenic Systemic Fibrosis (NSF), contact your local representative, or call customer service at (800) 362-2668.

References

1. MR Angiography (MRA). RadiologyInfo.org Web site. http://www.radiologyinfo.org/en/info.cfm?pg=angiomr. Accessed September 16, 2010. 2. ABLAVAR® [package insert]. North Billerica, MA: Lantheus Medical Imaging, Inc.; 2011. 3. US Food and Drug Administration Web site. http://www.fda.gov/drugs. Accessed September 16, 2010. 4. Magnevist® [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals, Inc.; 2010. 5. Omniscan™ [package insert]. Princeton, NJ: GE Healthcare, Inc.; 2010. 6. MultiHance® [package insert]. Princeton, NJ: Bracco Diagnostics, Inc.; 2010. 7. ProHance® [package insert]. Princeton, NJ: Bracco Diagnostics, Inc.; 2010. 8. Optimark™ [package insert]. St. Louis, MO: Mallinckrodt, Inc.; 2010. 9. Goyen M. Gadofosveset-enhanced magnetic resonance angiography. Vasc Health Risk Manag. 2008;4(1):1-9. 10. Lauffer RB, Parmelee DJ, Dunham SU, et al. MS-325: albumin-targeted contrast agent for MR angiography. Radiology. 1998;207(2):529-538. 11.Schwenke C, Kienbaum S, Bergmann, K. Health economic Benefits of Vasovist. In: Leiner T, Goyen M, Rohrer M, Schönberg S, eds. Clinical Blood Pool MR Imaging. Heidelberg, Germany: Springer Medizin Verlag; 2008:243. 12.Perreault, P, Edelman M, et al. MR Angiography with Gadofosveset Trisodium for Peripheral Vascular Disease: Phase II Trial. Radiology. 2003;229:811-820. 13. Bremerich J, Bilecen D, Reimer P. MR angiography with blood pool contrast agents. Eur Radiol. 2007;17(12):3017-3024. 14. Goyen M, Edelman M, Perreault P, et al. MR angiography of aortoiliac occlusive disease: a phase III study of the safety and effectiveness of the blood-pool contrast agent MS-325. Radiology. 2005;236(3):825-833. 15. Rapp JH, Wolff SD, Quinn SF, et al. Aortoiliac occlusive disease in patients with known or suspected peripheral vascular disease: safety and efficacy of gadofosveset-enhanced MR angiography—multicenter comparative phase III study. Radiology. 2005;236(1):71-78. 16. Huppertz A, Kroll H, Klessen C, et al. Biphasic blood pool contrast agent-enhanced whole-body MR angiography for treatment planning in patients with significant arterial stenosis. Invest Radiol. 2009;44(7):422-432. 17. Willinek W, Hadizadeh D. Patient management and referrals: impact of high-resolution steady-state MRA with Vasovist. In: Leiner T, Goyen M, Rohrer M, Schönberg S, eds. Clinical Blood Pool MR Imaging. Heidelberg, Germany: Springer Medizin Verlag; 2008:253. 18. Hadizadeh DR, Gieseke J, Lohmaier SH, et al. Peripheral MR angiography with blood pool contrast agent: prospective intraindividual comparative study of high-spatial-resolution steady-state MR angiography versus standard-resolution first-pass MR angiography and DSA. Radiology. 2008;249(2):701-711. 19. Data on file, Lantheus Medical Imaging, Inc.