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Bracco Imaging Customized Solutions Meet the Demands of an Evolving Radiology Market

Company Commitment to Providing Products, Services and Technologies to Promote Safety, Efficacy and Efficiency Demonstrated at RSNA 2010

CHICAGO, November 28, 2010 – Bracco Imaging S.p.A. – one of the world’s leading companies in the imaging agent business and part of the Bracco Group – is demonstrating how its customized evidence-based diagnostic imaging solutions are meeting the demands of an evolving radiology market at the 96th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA), which is being held November 28 - December 3, 2010 at Chicago’s McCormick Place, booth #4035.

Bracco continues to build on its longstanding commitment to safety, efficacy and efficiency at this year’s meeting, where the company is sharing clinical and scientific insights as well as regulatory progress related to its contrast media in Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Nuclear Medicine, Cardiac Catheterization, and Interventional/Diagnostic Radiology, and its contrast delivery systems.

“A number of factors are shaping the evolution of radiology today, including rapid innovation, cost control and an acute awareness of product safety,” said Carlo Medici, Head of Global Commercial Operations of Bracco Imaging S.p.A. and President and Chief Executive Officer, Bracco Diagnostics Inc. “By listening to the individual radiologist and focusing on evidence-based solutions for a more rapid, accurate diagnosis, Bracco is pursuing new standards for safety, efficacy and efficiency in diagnostic imaging.”

From the development of the first modern nonionic contrast agent in 1981 to the integration of protocols and contrast delivery platforms showcased at RSNA 2010, customer-driven innovation is a hallmark of Bracco’s integrated solutions approach.

Bracco’s diagnostic imaging products have outpaced growth in key areas due to its focus on high quality processes and products that are in tune with the needs of patients, physicians and the broader healthcare market. A defining example of this commitment is Isovue ® (iopamidol injection), a product whose supporting clinical evidence, versatile indications and availability in a convenient range of iodine concentrations and packaging options have made it the number-one low osmolar contrast media agent in the U.S. 1,2 - more -

1 Contrast Manufacturers Industry Group (CMIG) Market Data 2010, by W&W Services, Inc. 2 IMS DDD™ 2010, by IMS Health Incorporated Bracco Imaging at RSNA 2010

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The company also continues to see robust growth stemming from products and solutions related to its 2008 acquisition of E-Z-EM, Inc., one of the most recognized brands among radiologists and gastrointestinal (GI) physicians across several markets including CT Contrast, Delivery Systems, Workflow Solutions and Virtual Colonoscopy. Among these are the company’s injector and data management systems, which enable radiologists, administrators and technologists to gain workflow efficiencies, imaging optimization and patient safety benefits. Also, through this acquisition, Bracco is now the only provider of barium-based oral imaging products.

Safety, Efficacy and Efficiency in MRI

Bracco’s dual product portfolio of gadolinium-based contrast agents (GBCAs)—MultiHance ® (gadobenate dimeglumine) injection, 529 mg/mL, and ProHance ® (gadoteridol) injection, 279.3 mg/mL—are increasingly the MRI agents of choice by radiologists in more than 2,000 healthcare facilities in the U.S., as evidenced by five years of steady growth in a market that continues to recede. 3

MultiHance was the first and only contrast agent approved for MRI of the central nervous system (CNS) in the U.S., with twice the relaxivity compared to other tested extracellular contrast agents, which means greater contrast-to-noise and lesion-to-brain ratio, which may lead to improved visualization. ProHance is the only macrocyclic gadolinium contrast agent available in the U.S., with an exceptionally stable Gd chelate.

“Clinical and scientific data are defining the many differences between GBCAs, and the response from regulating agencies and the medical community is taking shape in real time,” comments Alberto Spinazzi, MD, senior vice president of group medical and regulatory affairs for Bracco Diagnostics. “MultiHance provides improved contrast enhancement due to its higher relaxivity, and both MultiHance and ProHance provide excellent stability, combined characteristics absent from other GBCA offerings. Understanding these characteristics is a function of our commitment to quality as well as clinical and scientific evidence, which have been recognized by both regulators and radiologists.”

Spinazzi continued, “Yet in addition to efficacy and safety, we understand the need for efficiency; the need to streamline processes and eliminate costs from the system. Incremental solutions, such as our innovative delivery and data management systems, add up to improved diagnostic capabilities with cost-effective and efficient technology.”

Nephrogenic systemic fibrosis (NSF), a rare and potentially life threatening syndrome in patients with renal impairment, has been associated with GBCAs. This has fueled significant clinical and scientific activity in attempts to determine the etiology of this disease. In response to the development of this disease and the current body of scientific information available, the U.S. Food and Drug Administration (FDA) recently published new guidelines defining specific classes of GBCAs based on risk of causing NSF. In a briefing document dated December 8, 2009, the FDA, in addressing the risk for NSF, wrote: “Of the 5 GBCs considered, the higher risk is associated with Omniscan, Magnevist, and OptiMARK while the lowest risk is associated with ProHance and MultiHance.” 4,5,6,7 - more -

3 Data on file 4 OMNISCAN™ (gadodiamide) injection, Full Prescribing Information. Princeton, NJ: GE Healthcare Inc.; 2007 5 MAGNEVIST ® (brand of gadopentetate dimeglumine) injection, Full Prescribing Information. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2010 6 OptiMARK ™ (gadoversetamide) injection, Full Prescribing Information. St. Louis, MO: Mallinckrodt Inc.; 2009 7 FDA Briefing Document, December 8, 2009 Bracco Imaging at RSNA 2010

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Per the FDA’s September 9, 2010 Safety Announcement, Omniscan, Magnevist and OptiMARK are now contraindicated for use in patients with acute kidney injury of any origin and in patients with severe chronic kidney disease. 8

Further, the American College of Radiology warned in its June 2010 version 7.0 of the Manual on Contrast Media that radiologists should administer GBCAs to renally impaired patients only where necessary, “using the lowest possible dose of GBCM required to obtain the needed clinical information, avoiding double or triple dose studies, and avoiding the use of those GBCM that have been most frequently associated with NSF.”

MultiHance was further differentiated by two updates to its prescribing information within the past year. The first reflects findings from two multicenter studies.9,10 Together, the studies demonstrate that MultiHance provides significantly greater diagnostic information and lesion visualization when compared to two other commonly used contrast agents used at an equivalent dose. The second labeling update reflects FDA approval of MultiHance for intravenous use in MRI of the CNS in children over two years of age, to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine and associated tissues.

About Isovue Isovue is a safe and effective nonionic low osmolar, low viscosity contrast agent well established with U.S. clinical experience since 1986. More than 270 million doses of iopamidol have been administered worldwide. 11 Indicated for a wide variety of radiographic, angiographic and CT indications, Isovue offers desired flexibility by providing a wide range of iodine concentrations and packaging options. Isovue-M is chemically identical to Isovue, but specifically packaged and labeled for intrathecal use. Clinical applications for Isovue-M include intrathecal administration in adult neuroradiology, including myelography, contrast enhancement of CT cisternography and ventriculography, and thoraco-lumbar myelography, in children over the age of two years old.

IMPORTANT SAFETY INFORMATION: Nonionic iodinated contrast media inhibit blood coagulation, in vitro, less than ionic contrast media. Clotting has been reported when blood remains in contact with syringes containing nonionic contrast media. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angiographic procedures with both ionic and nonionic contrast media. Therefore, meticulous intravascular administration technique is necessary, particularly during angiographic procedures, to minimize thromboembolic events. As with all injectable contrast agents, the possibility of severe reactions should be borne in mind, regardless of the patient’s pre-existing medical history. As with any other iodinated contrast media, caution must be exercised in patients with severely impaired renal function, combined renal and hepatic disease, combined renal and cardiac disease, severe thyrotoxicosis, myelomatosis, or anuria, particularly when large doses are administered. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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8 FDA Safety Announcement, September 9, 2010 9 Rowley HA et al. Contrast-Enhanced MR Imaging of Brain Lesions: a Large-Scale Intraindividual Crossover Comparison of Gadobenate Dimeglumine versus Gadodiamide. Am J Neuoradiology October 2008 29:1684-91. 10 Maravilla KR et al. Contrast Enhancement of Central Nervous System Lesions: Multicenter Intraindividual Crossover Comparative Study of Two MR Contrast Agents. Radiology 2006; 240: 389-400. 11 Data on file. Bracco Imaging at RSNA 2010

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About MultiHance MultiHance is the highest relaxivity gadolinium-based MRI contrast agent approved for use in the U.S. for MRI of the CNS. The clinical experience with MultiHance exceeds eight million doses administered worldwide.12

MultiHance is indicated for intravenous use in CNS MRI in adults and children over two years of age, to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine and associated tissues. 13 It has approximately twice the relaxivity of other available gadolinium-based contrast agents approved for CNS MRI in the U.S., providing a marked increase in signal, and in signal- to-noise ratio (SNR).14

Effective October 2, 2009, the FDA has approved a change in the Pharmacodynamics Section of MultiHance’s prescribing information to inform healthcare professionals that MultiHance may provide improved CNS visualization when compared with other gadolinium-based contrast agents, including Omniscan 4 and Magnevist 5. The new wording is:

Unlike other tested paramagnetic contrast agents (See Table 1), MultiHance demonstrates weak and transient interactions with serum proteins that causes slowing in the molecular tumbling dynamics, resulting in strong increases in relaxivity in solutions containing serum proteins. The improved relaxation effect can contribute to increased contrast-to-noise ratio and lesion-to-brain ratio, which may improve visualization. 13

MultiHance, with its higher relaxivity, and higher signal and SNR, improves visualization of smaller lesions and delineation of larger lesions of the CNS compared to Magnevist 5 at equivalent doses of 0.1 mmol/kg. 9,10

Lastly, as concluded in a recent study by Rumboldt et al, the diagnostic performance and contrast efficacy achieved with a MultiHance dose of 0.1 mmol/kg at 1.5T is maintained at 3T. 15

About ProHance ProHance is the first and only macrocyclic gadolinium-based MRI contrast agent available for use in the U.S. ProHance was launched in the U.S. market in 1992.

ProHance is indicated for use in MRI in adults and children over two years of age, to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues. ProHance is also indicated for use in MRI in adults to visualize lesions in the head and neck. 16

ProHance has the highest thermodynamic stability constant and conditional stability and the lowest osmolality of the nonionic agents. 17 18

The clinical experience with ProHance exceeds 13 million doses administered worldwide. 12 19

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12 Data on file 13 MultiHance ® (gadobenate dimeglumine) injection, 529 mg/mL. Full Prescribing Information. Princeton, NJ: Bracco Diagnostics Inc., 2010 14 Knopp MV et al. Primary and secondary brain tumors at MR imaging: bicentric intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine. Radiology 2..4; 230:55-64 15 Rumboldt Z, et al. Multicenter, Double-Blind, Randomized, intraindividual Crossover Comparison of Gadobenate Dimeglumine and Gadopentetate in MRI of Brain Rumors. JMRI: 2009; 29:760-767 16 Prohance ® (Gadoteridol) injection, 279.3 mg/mL Full Prescribing Information. Princeton, NJ: Bracco Diagnostics, Inc.; 2007. 17 Idée JM, Port C, Raynal I, et al. Clinical and geological consequences of transmetallation Induced by contrast agents for magnetic resonance imaging: a review. Fundamental and Clinical Pharmacology. 2006; 20:563-576.

Bracco Imaging at RSNA 2010

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IMPORTANT SAFETY INFORMATION FOR MULTIHANCE AND PROHANCE

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS

Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with: • Acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73 m 2), or • Acute renal insufficiency of any severity due to the hepatorenal syndrome or in the perioperative liver transplantation period.

In these patients, avoid use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast-enhanced magnetic resonance imaging. NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle, or internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium- based contrast agent, do not exceed the recommended dose and allow a sufficient period of time for elimination of the agent from the body prior to any readministration. (See WARNINGS)*.

As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life-threatening, or fatal anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic disorders. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For additional information, please visit http://usa.braccoimaging.com/products/imaging- modalities.html . Full Prescribing Information for all Bracco products, including the full list of indications, safety information and important boxed warnings where appropriate, is available at Bracco’s RSNA 2010 booth and in its RSNA 2010 press kit. If you have any questions of require additional information about any Bracco product, please contact Bracco Professional Services at 1-800-257-5181, option 2.

About Bracco Imaging Bracco Imaging S.p.A. is one of the World’s leading companies in the diagnostic imaging business. Bracco Imaging develops, manufactures and markets diagnostic imaging agents and solutions that meet medical needs and facilitate clinical solutions. Headquartered in Milan, Italy, Bracco Imaging operates in over 90 markets worldwide, either directly or indirectly, through subsidiaries, joint ventures, licenses and distribution partnership agreements.

Bracco Imaging is a subsidiary of Bracco S.p.A., the holding company of the Bracco Group which also markets Ethical and Over the Counter (OTC) pharmaceutical products in Italy as well as Medical Devices and Advanced injection systems for contrast imaging products worldwide. Furthermore, the Bracco Group offers diagnosis services through the Milan-based Centro Diagnostico Italiano (Italian Diagnostic Center).

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