This report originally appeared in the April 2011 issue of DOTmed Business News

Two images were presented to a skeptical radiologist at Little Company of Mary, a nonprofit, Catholic, community hospital. The angiography results for the images mirrored each other. "Alright, you have my attention," he told Kate Erickson, manager of imaging services at the hospital.

One image had been acquired using contrast, the other without. The results were so convincing that the hospital made the decision to go without contrast agents for many of its procedures.

"Non-contrast is a different way of approaching an MRI scan – it’s based on what the patient’s heart is actually doing, not on parameters plugged in," says Erickson.

An agent for change
Whereas today’s Gadolinium-based contrast agents (GBCAs) are relatively safe, the risks have been significantly curtailed since the 1950s when the first generation of iodinated contrast solutions was introduced. Even today’s more refined iodinated contrast solutions are associated with greater incidences of reactions than Gadolinium agents.

Although GBCAs are usually safe for the millions of patient who receive them every year, they are not risk-free. “It’s fair to say contrast agents, as injectionable drugs, do carry a risk of adverse reactions,” says Mark Hibberd, senior medical director of global medical affairs and pharmacovigilance for Lantheus Medical Imaging, a leading manufacturer of contrast agents. “Some of the newer agents are better, but adverse reactions can still be significant.”

Last year, the FDA required updates to warnings on contrast packaging to drive home the risk of nephrogenic systemic fibrosis, a rare and debilitating disease first discovered in 1997 and linked to the use of GBCAs on patients with compromised kidney functions.

Although reports of the connection trickled out, it wasn’t until June 2006 that the FDA released its first public health advisory acknowledging the relationship. By May 23, 2007, the agency requested a “New Warnings” section be added to packaging acknowledging the risk of NSF. Currently, the registry for the International Center for Nephrogenic Systemic Fibrosis has recorded over 355 identified cases of the disease. Further research into both prevention and cure is ongoing.

However, as Hibberd points out, agents are by no means created equal. “The ones used for CT and angiography are very different than MR, which is different from ultrasound, with ultrasound easily the safest. Iodinated contrast is the most dangerous, but within the class there’s subtle differences. In nuclear cardiology the safety tends to be very good. There’s obviously radiation exposure, but it’s kept to the absolute lowest level necessary.

“Among the Gadolinium-based agents, Ablavar, which Lantheus acquired over a year ago, has seen no cases of NSF so far.“

Hibberd says the dose for Ablavar (gadofosveset trisodium) is 1/3 to 1/10 less than other brands because it was specifically designed for MRA procedures. Currently, it’s only approved for vascular use, but there are independent investigations into its potential for tissue imaging.

It’s reasonable to expect differences among brands of contrast agents, but from time to time, the manufacturing process my inadvertently introduce differences from batch to batch. “Before, physicians might have prescribed contrast a little too freely. There wasn’t accountability about which patient got what batch, but the FDA is taking a closer look to see how it’s distributed. I think there’s going to be more talk about prefilled syringes,” says Scott Scofield, CEO of Vivid Imaging, a medical equipment service company.

Liquid gold’s boom and bust
There’s no denying the improved imaging capabilities provided by contrast solutions have been useful to the public and the medical community, even if profits aren’t what they once were according to Chuck Marshall, president and CEO for Florida Service Plus Inc. a service and training company specializing in injectors.

Marshall started his career in 1984 with a major injector OEM before moving on to open his current company in 1991. He’s had an opportunity to see some of the sector’s major financial shifts firsthand. “Eight years ago, the income derived from injector syringe sales was estimated at $150 million, while service was $35 million,” he recalls. “Contrast on the other hand, was like liquid gold. That part of the market was estimated at $3 billion.”

Today’s market tells a different story. Patents have expired on some contrast agents allowing the cheaper generics to seep into the market and undercut name brands. The recent reimbursement cuts haven’t helped matters. “Contrast’s taking hits from CMS reimbursements,” says Scofield. Profit margin per ml was maybe 10 to 15 cents in the past, now it’s very thin — single digits. Even the margins on generics are tight.”

That’s not totally preventing some pharmaceutical companies from trying though. On March 14, The U.S. Food and Drug Administration approved Bayer Pharmaceuticals’ Gadolinium-based contrast agent Gadavist, making it the sixth available on the market overall.

A sticking point
Overall though, the agent itself isn’t delivering the financial goods for manufacturers like it did in the past, so what’s to cause the sector from drying up as OEMs seek greener pastures? To put it simply, innovation is saving the day. Although patents may be expiring on pharmaceuticals and the extensive research and development followed by the lengthy and costly approval process make new releases few and far between, there’s still a revenue source and they’re much easier to find than the proverbial one languishing in a haystack.

Needles hold patents too, but unlike pharmaceuticals, OEMS are able to quickly bring new injector needles to market. And they have a clever way to make them “must haves.”As patents on older needles expire, the attachments accepting the now patent-free needle are phased out. Between the syringes and tubing, a steady stream of supplies leaves the manufacturing plants with a steady cash flow returning.

Meanwhile, with the updates to needles and injectors, a new income generator is emerging. “Once the injector is set up to only handle a pre-filled syringe, contrast agents and saline will start to pick up again,” Florida Service Plus’ Marshall believes.

That is of course, unless Toshiba America Medical Systems has its way.

Clear images, hold the contrast
Little Company of Mary employs Toshiba’s technology to provide those high-quality images sans the contrast. Economics plays multiple roles in this story as well.

Toshiba’s Vantage MRI system was welcomed overseas according to Stuart Clarkson, director of the MR business unit for Toshiba. “Starting in 1999, we investigated vessels and vascular structures difficult to image without Gadolinium. Our research was of particular interest in Japan where Gadolinium contrast-agents were never subject to reimbursement from the government.”




The positive for LCMH is that the facility’s introduction into non-contrast imaging involved fourth or fifth generation technology. That technology, with a current install base of 1,100 worldwide, still carries a significant price tag – ranging from $1.1 to $1.5 million depending upon the configuration.

But the outlay is just one side of the financial story. Erickson believes her hospital has probably already recouped the cost of the technology in the three years it’s been in use.

“We run between 48 and 55 procedures annually that traditionally required contrast,” she says. “We’re experiencing savings throughout our system and an improvement to the workflow surrounding procedures as well.”

Erickson points out that the lack of contrast agents means there’s no need for a lab draw prior to the procedure, so the disposables typically involved are no longer needed. Patients don’t have to have that extra task scheduled and there’s not the extra pay needed to cover staff expenses. A second source of savings is realized the day of the procedure when again, a needle isn’t needed for the IV.

There’s often skepticism from both staff and patients to deal with as well. “We’ve worked with patients who have been previously imaged in the past in other facilities who were very pleasantly surprised that we don’t need contrast —some asked to call their doctor to make sure the doctor was aware of non-contrast,” Erickson says.

Do-overs and details
Erickson points out an additional benefit with running a non-contrast imaging procedure that’s a benefit to both patient and provider. “In normal contrast-enhanced imaging, getting the bolus a must. In non-contrast imaging, you don’t run the risk of missing the bolus when it reaches the area to be imaged —you can reshoot over and over with no loss.”

But how does the technology work?

“Multi-phase imaging is used to visualize the blood flow as it courses through the renal arteries,” according to Clarkson. “So, a static one-time picture has evolved into flow dynamics. We have the ability to suppress signal from stationary tissue and make flowing blood bright. If we repeat this same scan with increasing delay times between the arterial tagging and imaging pulses, we can visualize the blood flow deeper into the imaging volume. The resulting images are then viewed as a movie loop which results in the multi-phase angiographic images —all done with no radiation and without an injection of Gadolinium."

The wishlist
With the technological foundation created six decades ago, contrast injectors and agents have had time to grow and mature. Better understanding of the imaging process and even of the interaction between contrast materials and the circulatory system on a cellular level is leading some to propose that the best is yet to come.

With the emergence of 3-D ultrasound, contrast agents are finding a new market and research is offering promise in other areas as well. “We have a new compound, Flurpiridaz, that’s a PET agent for myocardial imaging. We’re beginning our Phase III trials for registration. The Phase II data were very exciting and we will have presentation of the information at the ICNC [the European College of Cardiology] conference,” says Lantheus’ Hibberd. “It looks like a major advance in the ability to accurately detect heart disease.”

Lantheus has another PET agent that recently completed Phase I clinical trials. The company said it could help with the diagnosis of patients with heart failure by imaging the tissue structure.

On the equipment side, Toshiba has a few more irons in the fire as well. “We’re looking at ways to see the blood going further into the vascular tree. In this way, if someone has cancer, a liver lesion for example and medicine is being prescribed, we’ll be able to see how effective the treatment is and if it’s not effective, a different course of action can be taken. Obviously non-contrast imaging would be a great benefit to a patient with a liver lesion,” says Clarkson.

Toshiba is also teasing out a way to potentially look at pulmonary emboli —something commonly imaged in the imaging department. In most cases, the patient would get a CT scan to check for the ailment. Stuart believes they may be able to move it over to MR, giving pregnant women a safer non-radiation alternative.

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DOTmed Registered Injectors & Contrast Agents Sales & Service Companies
Names in boldface are Premium Listings.
Domestic
Chuck Marshall III, Florida Services Plus, Inc., FL
Moshe Alkalay, Hi Tech Int'l Group, FL
DOTmed Certified
David Denholtz, Integrity Medical Systems, Inc., FL
DOTmed Certified
DM 100
Patrick Miles, Med Exchange International, MA
DOTmed Certified
DM 100
Chad Seelye, Block Imaging International, Inc., MI
DM 100
Alison Fortin, Global Inventory Management LLC, NH
DOTmed Certified
DM 100
Ryan Gilday, Clinical Imaging Systems, Inc., NJ
DM 100
Robert Manetta, Nationwide Imaging Services Inc., NJ
DOTmed Certified
DM 100
Scott Scofield, Vivid Imaging, NV
Ian Alpert, Tandem Medical Equipment, Inc., NY
DOTmed Certified
DM 100
Stephen Maull, Maull Biomedical Training, LLC, OH
Sean Chen, Grand Medical Equipment, Inc., PA
DM 100
Robert Smith, Inter-Components, TX
Andy Stevens, Counterpane Inc., WA

International
Bruno Vandelanotte, Angiomedics, Belgium
Thomas Koenigbauer, MED & IT Trading, Germany
Vasant Sohoni, Vasant Sohoni & Associates, India
Silvano Gutierrez, Ruanova S.A. DE C.V., Mexico
Stefan Grozescu, Medisis, Romania

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