A Medical Device Daily

Using positron emission tomography (PET), the medical isotope 15O-water and cold pressor tests, Japanese researchers reported at the Society of Nuclear Medicine 's (SNM; Reston, Virginia) 53rd Annual Meeting in San Diego that they were able to detect the beginnings of atherosclerosis – before the disease became clinically evident.

This finding, they said, will allow physicians to advise high-risk patients, who show no cardiovascular symptoms, to make lifestyle changes or undergo medical treatment, said Masanao Naya, MD, a physician at Hokkaido University Graduate School of Medicine (Sapporo, Japan).

In addition, researchers determined that elevated levels of interleukin-6 – one of the inflammatory chemicals produced by endothelial cells and that has been associated with an increased risk of heart disease – is “a major determinant” of coronary endothelial dysfunction, especially in individuals with high blood pressure.

Josef Machac, cardiovascular vice chairman of the Society of Nuclear Medicine's Scientific Program Committee, in a prepared statement, called the findings of the study “quite revolutionary research. By measuring the response of coronary blood flow to stress, these researchers were able to detect atherosclerosis before it became evident clinically,” he said.

Atherosclerosis is a progressive disease that begins with damage to the innermost layer of the artery – the endothelium – and buildup of fatty substances, cholesterol and cellular waste products in the inner linings of arteries, which carry oxygen-rich blood to the heart, brain and other parts of the body. Over time, plaques narrow coronary arteries, allowing less blood to flow to the heart muscle, and rupture of these plaques may result in heart attack and death, said Naya, co-author of “Determinants of Coronary Endothelial Dysfunction in Hypertensive Patients.”

Naya explained, “We can select high-risk patients with endothelial dysfunction using blood sample analysis at an early stage of atherosclerosis, then start medical treatment or lifestyle modification.”

Coronary endothelial function is impaired at an early stage of atherosclerosis in hypertensive patients; however, the magnitude of dysfunction differs among individuals, said Naya. “We can assess the endothelial dysfunction in the human heart noninvasively using PET and evaluate factors that can determine endothelial dysfunction,” he added.

The researchers examined 27 untreated patients with high blood pressure. Myocardial blood flow was measured both at rest and during stimulation induced by a cold pressor test by using PET with 15O-water. The patient's feet were immersed in icy water for four minutes, and a person's risk for hypertension or high blood pressure was evaluated by observing blood pressure response.

Additional research needs to be done, said Naya. “We have been enrolling more patients and evaluating the relevance to the prognosis and the effect of medical treatments or life modification,” he noted.

In other SNM meeting news:

• GE Healthcare (Waukesha, Wisconsin) reported the introduction of Xeleris 2, an advanced nuclear medicine review workstation.

According to the company, a highlight of the new system is XFL (Xeleris Floating License), which allows in nuclear medicine the ability for clinicians to read and process NM images from their own PCs throughout the institution.

The system enables virtually all of a department's nuclear medicine imaging systems to connect to a single workstation, further accelerating the entire imaging process, the company said, made possible by GE's DirectConnects feature, which standardizes reading tools and calculation methods for different makes and generations of nuclear medicine equipment.

Featuring a user-friendly and intuitive user interface, Xeleris 2 enables the replacement and removal of many competitive devices, GE said, and modernizes older GE nuclear medicine cameras, adding newer and more efficient applications and serviceability tools while maintaining compatibility with old peripherals and archive media.

• Digirad (Poway, California), a provider of cardiovascular imaging services and solid-state nuclear medicine imaging products to physician offices, hospitals and imaging centers, reported the release of its new Cardius 3 XPO triple-head cardiac gamma camera.

The system introduces Solidium high-definition solid-state digital detector technology, a new design that allows imaging of patients weighing up to 500 pounds and offers up to 38% faster image acquisition times than conventional dual head systems.

• Researchers at Molecular Insight Pharmaceuticals (Cambridge, Massachusetts) reported the presentation of preclinical data on Azedra (Ultratrace iobenguane I 131, or Ultratrace MIBG), the company's lead oncology product candidate for the treatment of neuroendocrine tumors.

The studies were conducted in support of Azedra's initial clinical trials in adult patients with neuroendocrine tumors. Azedra is a targeted radiopharmaceutical designed to maximize delivery of therapeutic radiolabeled MIBG molecules so that neuroendocrine tumors can be effectively diagnosed and treated, and to minimize the amount of non-radioactive MIBG molecules that are delivered to the patient. The compound targets the norepinephrine transporter, which is over-expressed in certain diseases such as in neuroendocrine cancers.

Azedra data presented in a poster evaluated the pharmacokinetics, tissue distribution and efficacy of Azedra, compared with available 131I-MIBG. In the preclinical efficacy studies, data suggested that Azedra showed comparable efficacy to conventional 131I-MIBG in inhibiting tumor growth in a xenograft model of neuroblastoma.

Over a range of doses commonly seen in the clinic, there was demonstrable improvement in the dose response curve at all doses tested. Azedra demonstrated improved delays in tumor growth (i.e. no tumor growth for more than 47 days), while the conventional MIBG preparation inhibited tumor growth by 20 days. Tissue distribution studies suggested that Azedra had increased uptake compared with conventional MIBG in tissues that express the norepinephrine transporter. Pharmacokinetic parameters of both preparations were comparable in normal tissues. In a separate oral presentation, the company described the performance of the proprietary solid phase technology that underlies the method for producing Azedra.

Molecular Insight also presented preliminary data on MIP-190, its preclinical cardiovascular candidate to target cardiac angiotensin converting enzyme (ACE) for the potential assessment and monitoring of congestive heart failure. ACE is elevated during heart failure and inhibiting the enzyme is an established therapeutic approach to treating the disease. Researchers believe that an ACE-based imaging product with the ability to map ACE uptake in the heart would be of value in assisting physicians in assessing the extent of cardiac disease and in optimizing therapeutic options without having to wait for further clinical signs of disease progression.

Researchers described the synthesis and initial evaluation of imaging compounds based on a potent ACE inhibitor, lisinopril. The studies suggested that the lead candidate compound in the MIP-190 series retains its ACE targeting activity in vivo. Additional studies are underway to evaluate this compound in models of heart failure.