Image is Everything

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Kim Ribbink

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Research into the human genome and intricate studies of disease states are opening the door to personalized therapy. But for those therapies to reach the right target audience, accurate and early diagnosis of disease are essential. Amersham Health, which develops and markets diagnostic pharmaceuticals for diagnosis of heart disease, circulatory disor ders, lung disease, diseases of the brain, and cancer, as well as radiotherapy products for the treatment of cancer, is positioning itself to play a leading role in making the connection a reality.

“Amersham is playing a part in the move toward personalized medicine,” says John Padfield, Ph.D., CEO of Amersham Health and a director of the company’s parent, Amer sham Plc. “The pharmaceutical industry has two parts — the therapeutic side, which treats people, and the diagnostic side, which diag noses patients to find the right patient at the right time, and to get the right drug for the right outcome.” Before patients can be treated, according to company officials, they must first be diag nosed. Medical diagnostic products play a sig nificant role in making the invisible visible. This enables healthcare providers to expand and improve their abilities to detect and define the extent of disease for better treat ment. As Amersham Health moves in the direc tion of helping to shift the “whole basis of by Kim Ribbink Everything IS IMAGE The opportunity to match a patient’s diagnosis with the right drug is becoming more realistic, and with its platform of diagnostic products AmershamHealth is striving to be at the forefront of personalized medicine. medicine from “diagnosis and treatment” to “prediction and preven tion,” the company is reaching out to pharmaceutical companies with the goal to develop therapeutics and diagnostics in tandem. In January of this year, the company formed an alliance with Pfizer Inc. to link early and accurate diagnosis of disease with targeted effective therapy. Under the agreement, Pfizer is funding imaging research programs in Amersham Health’s Imanet business, a developing network of research centers using positron emission tomography (PET), the most advanced molecular imaging technique available. The research will be aimed at identifying new molecular diagnostic products based on library compounds in Pfizer’s research portfolio, whilst simultaneously using Amersham’s imaging technology to accelerate research decisions. There is an important role for rapidly advancing imaging technolo gy, including PET and a technology relating to Amersham Health’s Spin Signal, in facilitating early approval of new therapeutics. Spin Sig nal is anticipated to have a wide range of applicability within both med ical diagnostics and in life sciences. Amersham Health’s first target area is in highresolution ventilation imaging of the lungs. Such imaging techniques can be used in disease management to ensure effective use of therapeutics for devastating illnesses including DIAGNOSTIC trends 69 PharmaVOICE M a y / J u n e 2 0 02 Anatomy Function Perfusion Viability Metabolism Drug distribution/ molecular pathways/ molecular targets/ receptors/ binding sites XRay/CT Ultrasound SPECT MRI PET Targeted PET The Spectrum of Medical Imaging Parkinson’s and Alzheimer’s disease, heart disease, and COPD (chronic obstructive pulmonary disease). Amersham Health has the rights to develop and commercialize resulting diagnostics from this collabora tion. “One of the reasons we’re collaborating with Pfizer is to get comple mentary therapies — the therapeutic drug and diagnostic drug — to come out at the same time,” Dr. Padfield says. As such alliances develop, Amersham predicts that the development of diagnostic tests will enable physicians to pinpoint the characteristics of a type of cancer, or cardiovascular or neurological abnormalities. In 2001, according to Amersham, more than 700 million medical imag ing procedures were performed worldwide. And of these, about 110 million scans were “enhanced” or made possible with medical diagnos tic products. THE PLATFORM Amersham Health’s imaging portfolio consists of four medical imag ing modalities: XRay (including computed tomography or CT) — Omnipaque and Visipaque; magnetic resonance imaging, or MRI — DIAGNOSTIC trends Omniscan; radiopharmaceutical imaging — Myoview, DaTSCAN, and Neospect; and ultrasound — Optison. Additionally, the company has a radiotherapy platform, which includes OncoSeed, Rapid Strand, TheraSeed, and EchoSeed. Already Amersham’s imaging products give specialists the tools to make a more definitive diagnosis (see products box on this page for more details). Amersham focuses its diagnostic solutions on three core areas — car diology, neurology, and cancer — all of which are becoming more prevalent as the global population ages. Imaging is particularly wellsuited to assist in the diagnosis and management of such diseases and indeed, according to Amersham, statistics show that people older than 45 require three to four times as many investigations as those younger than 45. Agerelated diseases such as cardiovascular disease; neurological disease, including Alzheimer’s, stroke, and depression; and cancer are among the most common in industrialized nations and represent the highest cost burden to the healthcare system. “With the aging population growing as it is, there is a need to do more diagnosis on patients than there ever has been in the past,” says Daniel Peters, president of Amersham Health’s medical diagnostics business worldwide. “Anywhere from two to four times the number of procedures are conducted on patients older than age 50 to confirm clin ical diagnoses.” Radiopharmaceutical imaging always requires a diagnostic product, depending on the procedure. Each modality is rapidly evolving to meet the growing demands of healthcare requirements. Overall, the empha sis in technology advancement is to improve the speed, efficiency, and functionality of instrumentation, lower its costs, and thereby increase accessibility. Currently, imaging products are generally injected into the blood stream to enhance images of the structure or functioning of body organs and tissues obtained during diagnostic imaging procedures. These enhanced diagnostic images enable physicians to more accurately detect, diagnose, and treat diseases of the heart, lung, brain, and functional abnormalities. “The diagnostic physician, the cardiologist, the neurologist, and the 70 M a y / J u n e 2 0 0 2 PharmaVOICE ment of the central nervous system to detect lesions of the brain, spinal cord, and associated tissues. Omniscan is available in SafePak, a unique perprocedure system that permits proper dose delivery and features needlefree technology. . TESLASCAN (mangafodipir trisodium) is a liverspecific contrast agent. When injected intravenously, Teslascan aids in the detection, localization,characterization, and evaluation of liver lesions. Imaging can begin within minutes of injection, and additional scans can be taken up to 24 hours later without reinjection or loss of image quality. . CERETEC (technetium Tc 99m exametazime) is an imag ing agent with two distinct indications. One is for visualization of cerebral blood flow in stroke patients.The other is for labeling of white blood cells to localize intraabdominal infection and inflammatory bowel disease. . DATSCAN, a diagnostic for Parkinson’s dis ease, was launched in September 2000 in Amersham Health’s Product Portfolio Europe, and is the first marketed product that can distinguish true Parkinsonism from other conditions having similar symptoms but quite different treatment regimens. (In the U.S., the company has entered preclinical studies with Trodat, also for the diagnosis of Parkinson’s dis ease.) . INDIUMOXINE (Indium In111 oxyquinoline solution) is a diagnostic radiopharmaceutical intended for radiolabeling autologous leuko cytes (white blood cells). Leukocytes labeled with IndiumOxine are used to detect inflam matory processes to which leukocytes migrate, such as those associated with abscesses or other infections. After the patient’s blood is drawn and labeled with IndiumOxine, it is re injected and radiopharmaceutical imaging is performed,usually 24 hours after injection. . MYOVIEW (technetiumTc99m tetrofosmin), a cardiac imaging agent, is useful in the diagno sis and localization of regions of reversible myocardial ischemia in the presence or absence of infarction under exercise and rest conditions. Imaging can begin as soon as 15 minutes or up to four hours after administration of Myoview, enhancing patient management and department flexibility. In November 2001, the FDA approved the use of Myoview with pharmacological stress agents in patients with known or suspected coronary artery disease who are unable to exercise. . NEOSPECT, a new molecular diagnostic A mersham Health is actively managing and developing its portfolio of diagnostic and therapeutic products in the areas of cardiology,neurology,oncology,and pulmonology, which fall into four imaging modalities:XRay, including computed tomography or CT; magnetic resonance imaging,or MRI; radiopharmaceutical imaging;and ultrasound.The compa ny also markets brachytherapy seed implants for the treatment of prostate cancer. . OMNIPAQUE (iohexol) — a lowosmolar, nonion ic, iodinated contrast agent introduced in the 1985,has beenused in more than 100 million patients worldwide. Its indica tions include a broad range of intravascular diagnostic procedures such as coronary angiography,spinalcord imaging,andbody cavity procedures, including shoulder and knee joints. . VISIPAQUE (iodixanol), launched in 1996, is the only isosmolar contrast medium (IOCM) available in the U.S. With an osmo lality equal to that of blood, Visipaque was designed for patient safety and comfort. It also is the only contrast medium formulat ed with sodium and calcium in a ratio equivalent to blood. . OMNISCAN (gadodi amide) was launched in the U.S. in 1993 to provide contrast enhance XRay Radioimaging MRI DIAGNOSTIC trends oncologist can use one of our product offerings and the collective data so they know which tool to use to get the best information they can to make a diagnosis,” Mr. Peters explains. For example, in the case of XRay imaging, a cardiologist or radiol ogist might use Visipaque, an isosmolar contrast medium, to detect whether the vasculature is blocked. “Visipaque is injected intravenously or intraarterially, through a catheter, directly into the part of the anatomy in question,” Mr. Peters says. “A physician can insert a catheter right into the heart, inject the contrast agent, and get exquisite pictures. Because of its isosmolar nature Visipaque is very welltolerated by the patient.” Myoview is another one of Amersham’s leading radiopharmaceutical imaging products used predominantly for cardiovascular procedures. According to the company, Myoview can quickly and accurately demon strate which areas of the heart are affected and how serious the damage is. Myoview has proved so effective in visualizing blood flow to the heart that it’s used every 18 seconds to examine a heart patient in the U.S. “Myoview is injected intravenously,” Mr. Peters says. “It circulates through the body and is captured by the myocardial tissues of the heart. The radioisotopes that are attached to Myoview emit an image that is picked up by a gamma camera, and based on the intensity of the image the physician can determine if there’s full, blocked, or partial perfusion. This provides a very good picture for cardiac perfusion, which is critical to determine the effectiveness of cardiac function.” Omniscan is a MRI product that is used for vascular imaging as well as central nervous system imaging. The diagnostic contrast agent helps identify lesions or abnormalities in the body and the MRI equipment then captures an image of the blockage or tumor. Technologies such as MRI and CT have advanced, with the addition of contrast agents such as those from Amersham, aiding physicians in making the most effective diagnoses. “MRI was frequently heralded, as were many of the other technolo gies, as not needing the intervention of contrast agents for images,” Mr. Peters continues. “We have shown with Omniscan that while MRI and other technologies produce great images, when contrast agents are added they make images that are much more exquisite and allow physicians to make a more definitive diagnosis.” Amersham is working to expand the role of imaging beyond diagno 71 PharmaVOICE M a y / J u n e 2 0 02 product for the diagnosis of suspected lung cancer, was launched in April 2001. . OPTISON (human albumin microspheres) was launched in 2001 for imaging heart wall abnormalities. . ECHOSEED (Iodine125) is a new generation of brachytherapy seed, which was launched in 2001. EchoSeed’s patented technology uses conventional ultrasound imaging to provide physicians with more information about seed placement during the course of an implant pro cedure. . METASTRON (strontium89 chloride injec tion) is an intravenously administered radioiso tope that provides pain relief for patients suf fering from bonepaindue to metastatic cancer, and was approved by the FDA in 1993. The active agent, strontium89, is a calcium analog, and when injected into the bloodstream it tar gets areas where calcium uptake is seen,includ ing growing bone cancers. . ONCOSEED (Iodine125 Seeds) is indicated for permanent interstitial implantation (brachytherapy) of selected localized tumors with lowtomoderate radiosensitivity. OncoSeed may be used either as primary treat ment (for such diseases as prostate cancer or unresectable tumors) or for treatment of resid ual disease after excision of the primary tumor. . RAPID STRAND is the Rigid Absorbable Per manent Implant Device that consists of I125 seeds (welded titanium capsule containing I 125 adsorbed onto a silver rod) spaced at a fixed distance within an absorbable suture. RAPID Strand provides a method of implanting I125 seeds together in a line, ensuring more precise seed spacing and minimizing seed migration. . THERASEED,which was launched in 2001, is the leading Palladium103 prostate brachyther apy seed. . BEXXAR (tositumomab, iodine I 131 tositumomab), which has been filed with the FDA for the treat mentofnonHodgkin’s lymphoma,will bedevel oped and marketed in Europe by Amersham Health through an agreement with Corixa Corp. The product will be registered by Amersham Health under a different trade name in Europe. . NC 100668, a technetiumbased molecular diagnostic, was entered into Phase I clinical tri als in November 2001 for the detection of thrombus formation. This product initially will target the pulmonary embolism market. . OMNISCAN is in Phase III trials to extend the use of the MRI product in diseases of the cardiac and vascular systems.The trials are expected to be concluded in firsthalf 2002. . SONAZOID is being developed for the diagnosis of both heart and liver disease. In cardiology, Sonazoid entered Phase IIb doseranging studies to assess blood flow to the heart muscle following successful completion of Phase IIa efficacy studies. For the liver indication, Phase IIb clinical trials on Sonazoid were completed in Japan and Phase III clinical trials have commenced.The prevalence of primary liver cancer in East Asia is seven times higher than in the rest of the world. In the U.S. and Europe, Phase IIb trials for the liver indication also were com pleted,and subject to satisfactory indepen dent evaluation, Phase III trials are planned for the second half of 2002. . SPINSIGNAL is a technology in develop ment that will allow, for the first time, high resolution, highspeed imaging of gases using MRI. Amersham Health’s first target area for the technology is in highresolution ventilation imaging of the lungs.The clinical program is targeted at early detection,stag ing, and monitoring of lung diseases, and the first product stemming from the tech nology is Helispin, which is in Phase II clini cal trials. Ultrasound Radiotherapy In the Pipeline DIAGNOSTIC trends sis to predictive screening, which will detect disease earlier. For example, the company’s DaTSCAN product is being used to detect the first signs of Parkinson’s disease and differentiate this condition from other, less serious brain disorders. As new therapies and compounds evolve and become available for the treatment of Parkinson’s disease this imaging technique will become invaluable to treating the disease ear lier. Ultimately, the company’s goal is to diagnose disease before it becomes apparent. THEBIG PICTURE As the leading global pharmaceutical provider of diagnostic and pre dictive imaging products, Amersham has wellpositioned its products and technologies within the market (see “Global medical diagnostic market” box on page 74). The goal now is to continue to add to the pipeline as technologies for diagnosis develop, to find ways to bring diagnosis and therapy together, and to encourage clinicians to adopt these new technologies quickly. The company’s alliance with Pfizer is a definitive step forward to reaching the goal of more closely linking diagnosis and therapy, and of expanding its pipeline. Another milestone in bringing together the technologies to facilitate diagnosis was Amersham’s alliance in Novem ber 2001 with GE Medical Systems, a unit of General Electric Co. The research agreement’s goal is to accel erate the development of PETbased molecular diagnostic imaging tech nologies and systems. The first pro ject under this agreement involves the development of a PET synthesis system that will produce a new gen eration of targeted molecular radio pharmaceuticals. “We’re entering into alliances with companies such as Pfizer and GE Medical Systems as a way to add to our pipeline of diagnostic prod ucts and because of the pharmaceutical industry’s needs to get these comple mentary services to mar ket,” Dr. Padfield explains. “Our alliance with GE Medical tells us something about how, over the past five years, the industry has been converging. We’re all trying to achieve earlier, more accurate diagnosis, we’re trying to develop better treatments, and yes, we’re all trying to get dou bledigit profit growth.” Such molecular imaging techniques can be used in patients with a family his tory of Parkinson’s disease or Alzheimer’s disease to identify their chances of developing the illness and to target it with early therapy if necessary. For companies such as GE Medical or Siemens that sell multimillion dollar equipment such as CT or MRI machines, the need to link those technologies with contrasting agents such as Visipaque or Omniscan becomes more important as the technologies become more advanced. The goal of the GE Medical alliance ultimately is to deliver a nextgen eration “chemistry lab” that can output a number of innovative PET diagnostics with high disease specificity. Current PET synthesis systems that interface with cyclotrons are capable of generating just one diagnostic pharmaceutical, usually 18F fluorodeoxyglucose (FDG). The first products to be developed through this new PET synthesis system will be high pharmaceutical quality FDG and FDOPA, which is used to aid in the diagnosis and evaluation of Parkinson’s patients and cancer patients. The ability to target disease earlier has obvious farreaching conse quences. According to the Centers for Disease Control, cancer is the sec ond leading cause of death; one in four deaths is related to cancer, while Parkinson’s disease afflicts one in 100. Early detection, precise diagno sis, and effective treatment of these diseases are the basis for researching new PET diagnostics. “The way molecular diagnosis is going, whether they are gamma camera types of products such as with Myoview, or PET in the future, there is no picture unless there is a Myoview or a PETbased pharma ceutical product,” Dr. Padfield says. “Additionally, as we’re getting more and more into the molecular and cellular parts of the body, it becomes increasingly important to tag those parts in some way. It is necessary to have the chemistry and the biology working handinhand with the hardware and increasingly working with the software to provide exquisite images — allowing physicians to very quickly offer a diagno sis. A patient can’t be sitting in a $2.5 million machine for 25 or 30 minutes while the diagnostician scratches his head and tries to interpret the image.” 72 M a y / J u n e 2 0 0 2 PharmaVOICE With theagingpopulationgrowing as it is,there is aneedtodomore diagnosisonpatientsthan there everhasbeen in thepast. PETwillmake molecular imaging realand it will do it verysoon. Daniel L.Peters Dr.William Clarke DIAGNOSTIC trends According to William Clarke, M.D., M.Sc., executive VP of research and development at Amersham Health, PET imaging provides metabol ic and functional information about diseases that complements anatom ical imaging such as CT, MRI, or SPECT. “PET imaging can help physi cians provide earlier diagnosis of diseases and also provide rapid and quantitative assessment of a patient’s response to therapy.” “This truly is the future of PET imaging and molecular diagnostic science,” says Eric Stahre, general manager of genomics and molecular imaging at GE Medical Systems. “Our companies will take information learned from the mapping of the human genome to target early biomarkers of disease.” PET PROJECTS Positron emission tomography, or PET, is perhaps one of the most exciting developments in imaging technology in recent years. “Technology like PET is increasing the affinity between the diagnos tic target and the therapeutic receptor and the hardware, allowing for more precision and greater speed,” Dr. Padfield says. The technology itself has been around for about 25 years, but the growth and impact on patient care has only taken off in the past two to three years, the company explains. “PET has become an everyday clinical reality,” Dr. Clarke says. “It gives physicians that much more information to take that much better care of the patient.” PET is an advanced molecular imaging technique that combines com puter technology with procedures using chemicals that emit positrons (positively charged electrons). The technique requires shortlived radioac tive isotopes that are produced in a cyclotron and attached to a biochem ical molecule such as sugar, along with a hightechnology scanner. “The way PET works is that an atom is made that emits a positron, which is an antimatter electron,” Dr. Clarke explains. “This atom decays, gives off the positron, which hits an electron and then disappears, giving off gamma rays 180 degrees apart. A camera then takes a picture of where all those gamma rays came from, providing a very accurate placement of where that energy is.” PET can provide earlier diagnosis of diseases of the brain, the heart, and cancer. For cancer in particular, PET can detect early metases and/or recurrence of cancer before there are changes noted on physical exami nation or XRays, as well as differentiate postoperative or postradiation therapy changes from recurrent cancer. In addition, according to Amer sham, PETwill have an important role to play in postgenomic research. For example in medical research, PET will enable the identification of molecular changes linked to genetic disease, the effect of the environ ment on gene expression, and drug screening and development. PET technology enables the oncologist or general physician to pin point where a tumor is with greater precision than any other technolo gy on the market. “PET will make molecular imaging real and it will do it very soon,” Dr. Clarke continues. “In many ways PET is performing this function right now. Metastatic cancer is diagnosed with the current PET agent licensed in the U.S., which is FDG, a glucose analog. Radioactive fluo rine is tagged to a glucose molecule to make fluorodeoxyglucose (FDG), which is taken up by the patient’s cells. Cancer cells usually have increased metabolic activity and take up more radioactive glucose, which can be imaged by PET scans. The technology enables physicians to see tiny tumors. Regulators and reimbursers in the U.S. are now paying for PET scans because the technology dramati cally has shown the way a thera py is being directed.” Once therapy begins, PET also can be used to monitor a patient’s response to treatment. “For example, in the case of lymphoma, patients were often on a treatment, which is highly toxic, for longer than needed,” Dr. Clarke says. “Until recently, the physician would do an MRI scan during treatment to see whether the tumor was getting smaller. And even though the therapy may have killed, or is killing, cells from the lym phoma, the bulk of the tumor remains for some period of time. Now, after three weeks or less of chemotherapy for lymphoma, physicians are conducting a PET scan. Even though the size and the shape of the tumor are exact 73 PharmaVOICE M a y / J u n e 2 0 02 Amershamexecutives say theyhavethe platform fromwhich to initiate theprocess ofcreatingproducts forthe future. Oneof thechallengesasthepharma industry lookstomolecularmedicine, is finding therightpatient for that therapeuticagent.Atsomepoint there maybegenechiporgeneticbased predispositiontesting. Dr. JohnM.Padfield where the future lies. The link, we believe, will come through in vivo diagnostics or sophisticated ex vivo diagnostics.” Part of the challenge, Dr. Padfield says, lies in proving to regulators and payers the impor tance of determining the link between a spe cific strain of an illness and the drug designed to treat that disease. “If a company were able to demonstrate that a therapeutic drug gets to a specific tar get, then it might be possible to conduct clin ical trials on a smaller patient group,” he says. “It’s a lock and key analogy. How does a com pany prove that the therapy, or key, goes to the lock, or disease? For us, discovering the key to the diagnostic lock is important. We are work ing with the pharmaceutical industry to prove that the link between the target and the drug may speed products to the marketplace. As an industry our failure rate is not good — that’s ly the same, the scan shows if the tumors are dying in response to the therapy. In almost real time, therapy is starting to change for patients. That’s very powerful and that’s going to be the trend.” AVIEW OFTHE FUTURE As the pipeline of imaging agents advances, the opportunities for patientspecif ic diagnostics and then treatment will become a reality. And, Amersham executives say, they have the platform from which to initiate the process of creating products for the future. Molecular diagnostics that can visualize diseaserelated changes in the cells and molecules of the human body are advancing through the pipeline. Advances such as these will expand the role of imaging beyond diag nosis, playing a key role in the development of products for predictive screening, disease stag ing, selection of best therapy, and monitoring therapeutic efficacy and safety. “One of the challenges as the pharmaceuti cal industry looks to molecular medicine, is finding the right patient for that therapeutic agent,” Dr. Padfield says. Cracking the human genetic code has made personalized medicine a real possibility. The more scientists learn about genes and pro teins, say Amersham executives, the greater the realization that patients with the same symptoms, seemingly resulting from the same disease, don’t necessarily have the same root cause. The first step is to create accurate diag nostic tests and link these with targeted effec tive therapies, in essence linking the right drug for the right disease. According to Amersham officials, the next step is to study how the unique genetic profile of each individual affects which treatment is right for them. This affects how patients respond to drugs and ensuing side effects. When this causal relationship is fully under stood, companies will come close to delivering on the promise of “the right drug for the right patient.” “At some point there may be gene chip or geneticbased predisposition testing,” Dr. Padfield says. “But the challenge is finding the link between the existence of a certain gene and environmental exposure or other parts of a person’s makeup, which causes one individual to get a disease while another doesn’t — that’s just life. If we could double the success rate — imagine what that would mean economically. If we can increase the suc cess rate through the tools we provide, then that’s clearly an advantage to us, our shareholders, and patients.” In addition to winning over the clinicians and regulators to advanced technologies, thera peutic and diagnostic companies need to win over the patient, who may be disinclined to dis cover they have a predisposition to a disease until there is a therapeutic agent to treat the condition. “Medicine is going through a transforma tion,” Dr. Padfield says. “There’s a technolog ical component, which many companies are working on, but there are going to be very important sociological, governmental, and regulatory improvements required to bring these advances to the market. If the FDA, or other regulatory bodies, judge these new diag nostics in the same way they evaluate 20year old diagnostics, we’re not going to make the progress necessary to bring new treatments to market. There needs to be a new way of think ing about the regulations of complementary therapeutics and diagnostics.” F PharmaVoice welcomes comments about this article. Email us at DIAGNOSTIC trends 74 M a y / J u n e 2 0 0 2 PharmaVOICE Global Medical Diagnostic Market Amersham Health 37% Guerbet 1% Others 6% Schering AG 11% Tyco/Mallinckrodt 13% BMS/DuPont 14% Bracco 18% Source: Amersham Plc. Annual Report & Accounts 2001 Note: Marketshare figures are based on primary data collected in accordance with Best Practice Market Submissions and revised at least twice a year. Experts on this topic WILLIAM CLARKE,M.D.,M.SC.Executive VP of research and development, Amersham Health,a business of Amersham Plc., Buckinghamshire,U.K.; Amersham Health is the leading global pharmaceutical provider of diagnostic and predictive imaging products and services and related therapeutic products JOHNM.PADFIELD,PH.D.CEO,Amersham Health,and director of the company’s parent, Amersham Plc., Buckinghamshire, U.K.; Amersham Health is the leading glob al pharmaceutical provider of diagnostic and predictive imaging products and ser vices and related therapeutic products DANIEL L. PETERS.President of Amersham Health’s Medical Diagnostics business worldwide,Buckinghamshire,U.K.; Amersham Health is a business unit of Amersham Plc., and is the leading pharmaceutical company that provides diagnostic and predictive imaging products and services and related therapeutic products ERIC STAHRE. General manager of genomics and molecular imaging at GE Medical Systems,Waukesha,Wisc.;GE Medi cal Systems is a global leader in medical imaging, interventional procedures,health care services, and information technology

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