Nycomed and Diatide introduce TC-99m

Nuclear medicine physicians can now offer referring physicians a new diagnostic test that identifies acute venous thrombosis in the lower extremities. If left undetected, acute thrombi can lead to pulmonary embolism, a life-threatening condition.

In early October, Nycomed Amersham Imaging (Princeton, NJ) and Diatide, Inc. (Londonderry, NH) announced nationwide availability of technetium-99m apcitide (AcuTectTM), which received marketing clearance from the U.S. Food and Drug Administration (FDA) in September. Nycomed and Diatide have a co-promotion agreement for apcitide, for which Diatide said it received a $2 million "milestone payment" from Nycomed Amersham in September. "We have distribution agreements in place with all of the major radiopharmacies and most independent pharmacies," said Ronald B. Kinder, executive vice president and chief operating officer of Diatide.

Technetium-99m apcitide is a radiolabeled peptide that targets receptors on the cell surface of platelets that have become activated in the blood-clotting process. A peptide is an extremely small molecule made up of a handful of amino acids, like a tiny protein fragment. Diatide, Inc., a fairly new company in Londonderry, NH, specializes in radiolabeled peptides for both diagnosis and therapy. Apcitide is the company's first radiotracer to complete FDA review and enter the market, and the first imaging agent that targets acute deep-vein thrombosis (DVT). In medical journal papers, apcitide is sometimes called "P280."

"P280 has been shown in Phase III multicenter clinical trials to have a relatively high diagnostic accuracy for deep-vein thrombosis. We are planning to use it to distinguish between recurrent deep-vein thrombosis and postphlebitic syndrome, which is inflammation of the vein," said Raymond Taillefer, MD, director of the Nuclear Medicine Department at Hospital Hôtel-Dieu de Montreal, Québéc, Canada. "It's important to make this distinction because deep-vein thrombosis is treated with anticoagulants whereas postphlebitic syndrome is treated with other types of drugs," said Dr. Taillefer, who participated in clinical trials for apcitide.

Advantages of technetium-99m apcitide vs. ultrasound and venography

"The advantage of apcitide is that we are actually looking at active blood clotting using physiologic nuclear medicine images. With anatomic images, provided by ultrasound and contrast x-ray venography, we can see an anatomic abnormality that may or may not be an active thrombus," said Robert F. Carretta, MD, director of the Nuclear Medicine Department at Sutter Roseville Medical Center, Roseville, Calif.

"Another advantage of apcitide is that we can image shortly after injection and get the report to the referring physician very quickly. It will not replace ultrasound, which is an excellent screening procedure. But ultrasound has its limitations in the calf veins, and often does not detect acute deep-vein thrombosis below the knee," said Dr. Carretta, who also participated in apcitide clinical trials.

May replace venography gold standard

Acute and chronic DVT result in similar symptoms but can lead to radically different complications, costs, and treatment protocols. In addition, about three-quarters of patients with suspected DVT actually have nonthrombotic causes of leg pain.1

Apcitide is designed to complement ultrasound in discerning acute (active) from chronic blood clots. DVT-commonly formed in the iliac, femoral, or popliteal veins-is a major complication for many patients who undergo orthopedic surgery.2 This disorder is associated with cancer and other chronic diseases, as well as trauma. Venous thrombi are deposits of fibrin, red blood cells, platelets, and leukocytes. They usually form in regions of slow or disturbed blood flow in sinuses or valve cusp pockets in the deep veins of the calf. Symptoms typically include leg swelling, warmth, pain, and tenderness.

Contrast venography (phlebography) is considered the gold standard for diagnosing DVT.2,3 However, contrast venography is not routinely used because of time, expense, patient discomfort, and safety issues.3 In a joint statement released by Diatide and Nycomed, the companies stated that apcitide could potentially replace contrast venography as the new gold standard for identifying DVT. Venous ultrasound, often combined with color Doppler, has good sensitivity in patients with symptoms of DVT above the knee.2 However, ultrasound has a lower accuracy for DVT below the knee and in asymptomatic, high-risk patients.2

2 million DVT cases/year, 60,000 PE deaths/year

According to the American Heart Association, DVT occurs in approximately 2 million Americans each year.2 An estimated 600,000 patients develop pulmonary embolism (PE) each year, leading to about 60,000 deaths from this complication.2 About 70% of PE cases arise from DVT of the lower extremities.3

Anticoagulants, such as heparin, provide effective therapy to prevent PE in patients with DVT, but treatment must be continued for weeks or months after diagnosis of the acute event.2 Additionally, anticoagulant therapy is associated with increased risk of major bleeding and thrombocytopenia.1,3 Heparin may be the most common cause of drug-related death in reasonably healthy patients, with a morbidity of 30% and mortality of 2%.3 In light of these risks, apcitide could fill an important clinical need in differentiating acute DVT from chronic DVT, which has a lower risk of embolism that may not warrant the risks of anticoagulant therapy. In addition to the safety concerns, referring physicians also want to avoid unnecessary anticoagulant therapy because of the cost of medication and hospitalization.

Future indications?

Besides detection of DVT, technetium-99m apcitide may show potential in detection of PE, arterial thrombi, and vascular tumors.4

References

1. Anand SS, Wells PS, Hunt D, et al: Does this patient have deep vein thrombosis? JAMA 279:1094-1099, 1998.

2. Hirsh J, Hoak J: Management of deep vein thrombosis and pulmonary embolism: A statement for healthcare professionals from the Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation 93:2212-2245, 1996.

3. Pearson DA, Lister-James J, McBride WJ, et al: Thrombus imaging using technetium-99m-labeled high-potency GPIIb/IIIa receptor antagonists. Chemistry and initial biological studies. J Med Chem 39:1372-1382, 1996.

4. Muto P, Lastoria S, Varrella P, et al: Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide P280. J Nucl Med 36:1384-1391, 1995.

Worldwide release of Ensemble Tissue Harmonic Imaging technology

At the Radiological Society of North America (RSNA) annual meeting, to be held November 29 through December 4, 1998, in Chicago, Eastman Kodak Company (Rochester, NY) plans to introduce a new product line to help radiology departments better communicate images and reports to referring physicians. In addition, Kodak will exhibit the new Kodak Digital ScienceTM medical image server, basic web viewing software, and enhanced web viewing software.

At the meeting, the company will also announce enhancements for the Kodak Digital Science medical viewing stations, including enhanced patient foldering, report display, enhanced image processing, multiuser capability, and cine mode. Enhancements to Kodak Digital Science medical image and information libraries will include a global query to search for images across all archives in the network; compression choices, which include "lossless" compression and selectable levels of "lossy" compression; and a workflow module that includes enhanced "autorouting" and "pre-fetching" capabilities.

At the end of September, Siemens Medical Systems, Inc. Ultrasound Group (Issaquah, WA) announced the worldwide release of EnsembleTM Tissue Harmonic Imaging technology. According to Siemens, this technology enables the SONOLINE® Elegra ultrasound system to "isolate harmonic signal data, using signals from the entire broadband harmonic spectrum," resulting in clearer images without the use of contrast media.

"I initially used it [tissue harmonic imaging] in patients who were technically difficult to image, usually due to large body habitus, especially for viewing deep organs. Liver lesions, kidney lesions, kidney stones, and gallstones are made easier to see, with greater contrast resolution and without the loss of spatial resolution that previously occurred with the need to use a lower frequency for better tissue penetration," said Steven Winn, MD, of Alexandria Hospital (Alexandria, VA). "Ultimately, I believe tissue harmonic imaging will become as integral a part of the abdominal ultrasound exam as color Doppler is a part of vascular ultrasound," said Dr. Winn.

GE introduces wide-open, high-field MR

In mid-September, GE Medical Systems (Milwaukee) announced the addition of a new wide-open, high-field system to its line of magnetic resonance (MR) systems. The Signa® MR/i , to be available at both 1.0 and 1.5 tesla, uses the CX magnet that GE introduced last year. "In simple terms, we've married the look and feel of open MR/i systems with the performance of an advanced high-field system," said Gene Saragnese, MR global general manager of GE Medical Systems.

The market for open MR systems has shown strong growth over the past two years, according to GE. The Signa MR/i system features a 60-cm bore opening with a 70-cm length and 172-cm magnet length.