November 13 Features

Acusphere preps novel ultrasound agent for FDA submission

Phase III data indicate Imagify could compete with nuclear perfusion

A novel ultrasound contrast agent being groomed to replace nuclear cardiac perfusion will soon be on reviewers' desks at the FDA. The timing couldn't be better--or worse. Perfusion stress echo when performed with developer Acusphere's Imagify, promises advantages over nuclear stress testing in terms of quicker results, lower cost, and zero exposure to radioactivity. But Imagify is coming along at a tough time. Just weeks ago, the agency slapped a black box warning on two ultrasound agents already on the U.S. market, Optison and Definity, citing concerns that they may have been involved in the deaths or serious injury of several patients.Imagify can emerge from the shadow cast by these warnings, say the luminary who ran its international testing program and the Acusphere executive who will be in charge of its marketing. The agent is not only safer but also more effective and more clinically useful than ultrasound agents now on the market, they told DI SCAN. Data presented Nov. 6 at the American Heart Association meeting demonstrate that Imagify can compete effectively with nuclear stress testing to evaluate chest pain in patients at risk of a heart attack, said Dr. Roxy Senior, lead investigator of the phase III trials and director of echocardiology at Northwick Park Hospital and the Imperial College of Medicine in London, U.K.Subjects were split between two phase III trials, RAMP (Real time Assessment of Myocardial Perfusion)-1 and -2. The first involved 285 subjects with angina, the second, 377 subjects. Investigators compared accuracy, sensitivity, and specificity of perfusion stress echo using Imagify with nuclear stress testing. "The results clearly suggest that Imagify is as accurate as nuclear techniques to detect coronary artery disease," Senior said.Mona Haynes, vice president of marketing and sales for Acusphere, and her colleagues plan to submit those data early next year as part of the company's new drug application to the FDA. Where it goes from there is up to the FDA, she said."We will probably have a better feel as we approach the Prescription Drug User Fee Act date in terms of questions the FDA are asking and whether they are beginning the labeling discussions," she said.Haynes said she is not concerned that the FDA recently mandated black box warnings for the ultrasound contrast agents now on the U.S. market. Imagify has a better safety profile than either agent due to its unique construction, Haynes said.Only mild and transient adverse effects appeared throughout the clinical testing and these were resolved without long-lasting consequences. Most common were headache, chest pain or discomfort, and nausea and flushing, which occurred following the administration of dipyridamole used as an alternative to exercise stress.One reason for the improved safety profile, according to Senior, is the agent's structure. Instead of microbubbles, Imagify is composed of microspheres crafted from a synthetic material that dissolves in the body."They don't contract and expand as microbubbles do," Senior said. "That will minimize whatever issues the FDA might have with the agent."The agent was administered to more than 1000 subjects with no serious side effects, he said. Almost 700 of these subjects participated in the last phase of these trials, during which investigators compared contrast-enhanced echo using Imagify at stress and at rest with nuclear stress/rest testing in patients being evaluated for inducible ischemia. These tests differentiate Imagify from ultrasound contrast media currently on the market, namely GE's Optison and Bristol-Myers Squibb's Definity, which have not been proven clinically effective in visualizing cardiac perfusion. "Imagify is the first ultrasound contrast agent to be tested in this manner," Senior said.Optison and Definity are approved in the heart only for left ventricular opacification. Like these other agents, Imagify will enable assessment of wall motion--but it will also visualize blood flow. When combined, data from these two tests will serve as a stronger predictor of coronary artery disease than either finding alone, according to Dr. Michael Picard, director of clinical echocardiography at Massachusetts General Hospital Heart Center in Boston and clinical monitor for Imagify testing conducted at the hospital.Adding to Imagify's appeal will be its ease of use. Contrast-enhanced ultrasound is much easier to perform than nuclear perfusion. Ultrasound images can be acquired at the patient's bedside, as Imagify can be administered with a slow bolus injection. Perfusion data then can be generated for up to five minutes.

Cardiac IT morphs to handle images and patient data

Vendor consolidation drives system integration

Demand is rising for integrated IT cardiology products that provide images and nonimage data, according to the IMV Medical Information Division. This demand has given rise to a new breed of information technology, one that combines the capabilities of cardiology PACS and cardiovascular information systems.Feeding the development of these systems has been a raft of corporate consolidations over the past three years. These include the merger of Philips Medical Systems and Witt Biomedical, GE and Dynamic Imaging, McKesson and Medcon, Agfa and Heartlab, Emageon and Camtronics, and Fuji and ProSolv.This consolidation will be good for the imaging community as it will likely lead vendors to consider integration issues early in the planning stages of future CPACS and CVIS installations, according to Mary C. Patton, director of market research at IMV."Ultimately the customer will benefit from that," she told DI SCAN, "because after the initial cost of the system, integration issues are the biggest concerns that people have in implementing these kinds of systems."The IMV survey showed that two-thirds of the hospitals that have a CPACS/CVIS system are planning to upgrade, replace, or add new capabilities over the next three years.Two factors are driving this. One is the need for efficiency, which requires that images be provided in the context of nonimage patient information, such as hemodynamic monitoring and EKG data. The second is the extension of CT and MR into cardiovascular imaging, and advances in PET/CT and SPECT."Hospitals looking to implement CPACS in the next two to three years are looking at a broader range of modalities than have been included in these systems in the past," Patton said.In the just-released report, "The Cardiology Information Continuum: Present Access and Future Integration Strategies for Cardiovascular Image and Information Systems," IMV analysts examined responses from a random sample of 202 hospital administrators, which included those in charge of cardiovascular services, IT/MIS, CPACS, and radiology.Respondents stated that cardiac cath and echocardiography images, along with structured reporting, are the highest priorities for inclusion in cardiovascular information services systems. IMV analysts found the current reality, however, to lag behind these intentions. Most CPACS/CVIS systems now in place are more likely to provide access to cardiology images only and not provide a fully integrated structured reporting capability. The reason is simple. Separate radiology and cardiology PACS are being integrated in stages, rather than all at once. This integration is done using certain building blocks found in common data archive infrastructures, common databases, workstations, and image visualization software.Although a majority of PACS users have begun this process, many have integrated only one or two components. A substantial number--about 45% of respondents in the IMV survey--still have not integrated any."Many larger hospitals that began implementing cardiology PACS in 2004 and 2005 are now grappling with the issues of integration and are looking to vendors to help them address those issues," Patton said.

Contrast agent illuminates breast cancer with near-infrared light

Pam800 binds to microcalcifications, fluoresces NIR

Simple, low-cost, and free of the radiation risks associated with x-ray mammography, near-infrared radiation appears on the verge of becoming the next great advance in breast cancer detection. Although highly promising, the technique's inherent scattering of photons limits spatial resolution. As a result, small tumors can go undetected. Effective contrast agents that target the physiologic and molecular signs of tumors have been lacking.Now researchers at Beth Israel Deaconess Medical Center in Boston may have the answer. They have developed a contrast agent that targets the microcalcifications related to cancerous breast tumors. The agent, Pam800, is derived from pamidronate, an osteoporosis drug, and labeled with a dye that fluoresces in the presence of near-infrared light. This drug, a bisphosphonate, preferentially binds to calcium, which means Pam800 lights up bone but also the microcalcifications that appear along with breast cancer--or at least it should. Pam800 so far has been tested only in swine.Using NIR after administering Pam800 in pigs, Dr. John V. Frangioni, an associate professor of radiology at Beth Israel, and his colleagues have successfully detected tiny hydroxyapatite crystals deposited in the animals' soft tissue. Hydroxyapatite, a salt containing calcium and phosphate, is the same material found in the microcalcifications that accompany breast cancer.The successful animal tests put the Boston researchers on track to develop an NIR-based imaging technique they hope will selectively reveal malignant tissue in the human breast. The technique might even provide the basis for image-guided surgery. The road ahead involves a good bit of translational science from animal to human, but it may also afford a bonus. Because hydroxyapatite is present in bone, the NIR-based technique might provide other visualizing opportunities, and might vastly extend the utility of NIR to radiography.

PET scans may clear path for noninvasive lung cancer treatment

Stereotactic body radiotherapy uses PET as proof of efficacy

Finding the right balance between invasive and noninvasive treatment can be tricky, especially in radiation oncology. Some luminaries in this field have proposed the use of stereotactic body radiotherapy to treat small, primary lung cancers. The noninvasive technology, which involves pinpoint administration of high-energy radiation, is already applied in patients who are not candidates for surgery. But oncologists are reluctant to try it on surgical candidates without proof of clinical efficacy. PET/CT might provide that proof and the means for ensuring that lung cancer patients do not miss out on any treatment opportunities.Researchers from Fox Chase Cancer Center in Philadelphia, PA, presented data last week at the American Society for Therapeutic Radiology and Oncology's meeting that showed metabolic response as monitored by FDG-PET at three months post-treatment may be an early indicator of failure in patients who received stereotactic body radiotherapy. This may allow for timely salvage surgery in patients who need it, and can provide the rationale for using stereotactic body radiotherapy among those who can be treated surgically."Our study appears to show PET scans at three months following treatment allow an earlier and more accurate method to evaluate tumor response," said Steven Feigenberg, M.D., an attending physician in the department of radiation oncology at Fox Chase. "Confirming these findings is critical so that we can scientifically compare stereotactic body radiotherapy with surgery for these small tumors."