August 11, 2008

SNM Reporter’s Notebook
Radiology Today
Vol. 9 No. 16 P. 14

Editor’s Note: This article is compiled from information provided by the Society of Nuclear Medicine’s (SNM) media relations staff at the 55th annual meeting held June 14 to 18 in New Orleans.

New Test Could Aid Children Suffering From Reflux Disease
A scintigraphy exam was used to confirm that children with respiratory problems may be more likely to develop gastroesophageal reflux disease, according to research presented at SNM’s annual meeting.

Scintigraphy was also shown to be more effective for detecting the disease in these children than traditional barium x-ray technology. The results indicate that scintigraphy could become an important diagnostic tool for detecting reflux disease, a serious condition that can lead to chronic chest pain, vomiting, weight loss, and lung impairment in children.

“Unfortunately, reflux disease is a common problem in children, especially for those with respiratory problems,” said Wajiha Nasir, a researcher at the Nuclear Medicine Oncology and Radiotherapy Institute in Islamabad, Pakistan. “If left untreated, the disease can seriously impede children’s health, growth, and development, not to mention their quality of life. Our results show that scintigraphy is highly effective at safely diagnosing the condition.”

In this study, 55 children aged 6 months to 12 years who had asthma or lower respiratory tract infections were orally administered a commonly used radioactive imaging agent that was then detected through scintigraphy technology.

The test detected reflux disease in 66.6% of the children, revealing a strong association between reflux disease and respiratory disease. In addition, scintigraphy proved more effective at detecting the disease than traditional barium x-rays. Children in the study who exhibited reflux disease were given medication to treat it. At a three-month follow-up visit, most of the children’s symptoms had improved.

“Scintigraphy is one of the simplest radionuclide tests to administer, with a very low radiation burden,” said Nasir. If performed routinely for children suffering from bronchial asthma and recurrent respiratory tract infections, this test could get children the treatment they deserve.”

Individualized Therapies for Non-Hodgkin’s Lymphoma
PET could be an important tool for identifying non-Hodgkin’s lymphoma patients likely to respond well to treatment with 90 ibritumomab tiuxetan (IT), the first radioimmunotherapy treatment approved for use by the FDA, said researchers at SNM’s annual meeting.

PET allows practitioners to identify patients who could be treated, predict how they would respond, and identify relapses early in patients who have follicular lymphoma, a common type of slow-growing lymphoma.

“This study illustrates how PET could be used to advance the goal of personalized medicine, identifying and targeting the right treatment for each individual,” said researcher Stefano Fanti, MD, a professor of nuclear medicine at the Policlinico S. Orsola-Università di Bologna in Italy. “The functional data provided by PET are essential for determining stages of cancer, detecting disease relapses, and evaluating how patients respond to particular therapies. Our study clearly indicates that the next step—using PET for predicting how patients will respond to treatment—can be achieved.”

In the United States, about 65,000 new cases of non-Hodgkin’s lymphoma are diagnosed annually. The number of new cases is on the rise, especially among older people and those whose immune systems are not functioning normally, such as people who have had organ transplants and those with HIV.

IT is a monoclonal antibody used in conjunction with radioactive medications to treat non-Hodgkin’s lymphoma patients who have relapsed after treatment or for those with slow-growing forms of the disease such as follicular lymphoma. While there have been studies to investigate the usefulness of PET in patients with lymphoma and research into the effectiveness of radioimmunotherapy, no data were available regarding the role of PET in determining whether patients would be good candidates for 90 IT therapy.

In their study, Fanti and his team examined 38 non-Hodgkin’s lymphoma patients who were treated with 90 IT after a relapse. PET scans were taken before 90 IT treatment and then three months after treatment began. All patients had a final assessment at six months using clinical data.

Results indicated that the first set of PET scans detected the relapse and extent of the disease in all of the patients. At the six-month follow up, 89% of the patients were either in complete or partial remission after the 90 IT treatment. Comparison of PET data on the extent of patients’ disease at relapse and their response after three months indicated a higher rate of response to the treatment in patients whose cancer was limited. In all of the cases, the PET scan findings at three months were consistent with the clinical findings at six months.

Studying PET/CT for Staging Ovarian Cancer
PET/CT scanning of patients with early-stage ovarian cancer can enable physicians to determine whether the cancer has spread to nearby lymph nodes without performing surgery, according to researchers at SNM’s annual meeting. As a result, unnecessary surgeries could be reduced, which presumably would lower morbidity rates and postoperative complications for ovarian cancer patients.

“Our preliminary research indicates that using PET/CT scanning in this way could greatly improve quality of life for many patients with ovarian cancer,” said Luca Guerra, MD, a doctor of nuclear medicine at San Gerardo Teaching Hospital in Monza, Italy, and the study’s lead researcher. “PET/CT scans could allow many women to forego major abdominal surgery to determine whether their cancer has spread. It’s a much safer alternative for determining the stages of ovarian cancer.”

Unlike many other types of cancer, there is currently no reliable screening test to determine whether a woman has ovarian cancer. Although CT and MRI technologies are useful in determining the need for surgery in advanced cases of the disease, both have limited accuracy in determining stages of ovarian cancer.

While systematic lymphadenectomy (surgically removing all the lymph nodes for testing rather than sampling a small number of the lymph nodes) is more accurate for determining whether the cancer has spread, the surgery takes longer, often requires blood transfusions, and can result in life-threatening complications. If all early-stage ovarian cancer patients underwent lymphadenectomy, approximately 75% of the surgeries would prove unnecessary.

In their research, Guerra and his team examined results of 30 women diagnosed with ovarian cancer who underwent PET/CT scanning before surgery to determine the stage of their disease. The results indicated that PET/CT staging was correct in 67% of patients and more than 98% accurate in scanning the lymph nodes of stage 1 and 2 ovarian cancer patients. The results need to be confirmed in a larger patient population.

While most previous studies examining the potential of PET technologies did not indicate a definite role in the staging of ovarian cancer, many involved very small groups of women, and the scanners used were simple PET scanners rather than state-of-the-art, combined PET/CT scanners.

A New Weapon for Fighting Treatment-Resistant Cancers?
A gene radiotherapy system that detects and treats cancer cells resistant to traditional forms of chemotherapy and radiation showed success in the laboratory and could eventually prove beneficial for cancer patients, according to researchers at SNM’s annual meeting. The new system targets oxygen-deficient hypoxic cancer cells that have activated a gene known as HIF-1, which ensures the cells’ survival and makes them unresponsive to most current treatments.

“These types of cancer cells pose a significant challenge in treating many patients,” said June-Key Chung, MD, PhD, a professor of nuclear medicine at Seoul National University College of Medicine in South Korea and the lead researcher of the study. “Our research shows that this system successfully targets these hard-to-treat cells in vitro. Eventually, it could offer a novel way to develop new therapies for drug- and radiation-resistant cancers.”

Hypoxic cancer cells are found in solid tumors that develop in many different cancers, including those of the liver, breast, prostate, and uterus. Solid tumors undergo a multitude of cytogenetic or genetic changes over many years, some of which may resist almost any standard therapy.

“It is well known that hypoxic cancer cells are resistant to chemotherapy and radiotherapy, therefore creating a real dilemma for cancer therapies,” said Chung. “Now, we are hopeful that new therapeutic models targeting resistant cancers, which are currently under development in the laboratory, can be successfully used for treatment. The results of our research imply that this is a real possibility.”

Hypoxic cancer cells do not develop adequate blood vessels to receive oxygen. Because cells need oxygen to survive, hypoxic cells instead activate the HIF-1 protein, which changes cells’ metabolism and enables them to burn sugar for energy without oxygen. Traditional cancer therapies are ineffective against hypoxic cells that have activated HIF-1 because the protein regulates several genes related to the resistance of conventional cancer therapy.

In their laboratory research, Chung and his team developed a therapeutic system that targets HIF-1 human liver cancer cells. A reporter gene was developed that would express human sodium iodide symporter in the cancer cells. This gene would simultaneously track the cancer cells and treat them by allowing them to absorb iodine and radioisotopes more easily. To improve imaging of the cancer cells even further, researchers also engineered the reporter gene to become fluorescent when it encountered HIF-1 liver cancer cells so they could be tracked with optical imaging techniques. The reporter gene was then injected into human liver cancer cells. The results indicated that the system not only killed hypoxic liver cancer cells but also could eventually be useful for visualizing how HIF-1 activation occurs in these cells.

PET Assesses Stimulant’s Purported Ability to Improve Mental Performance
Concerned by the growing number of people using stimulant medications such as methylphenidate to improve attention and focus, researchers used PET with fluorodeoxyglucose (FDG) to study the drug’s effects on brain function in the normal human brain.

“Methylphenidate is often prescribed appropriately for individuals with attention-deficit/hyperactivity disorder [ADHD] who are unable to focus their minds in order to perform everyday tasks,” said Nora D. Volkow, MD, director of the National Institute on Drug Abuse in Bethesda, Md. “We wanted to better understand how the drug works in ‘normal, healthy’ people when they are performing a cognitive task, as well as when they are not.”

The study comprised 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task involving numerical calculations and when viewing cards with nature scenes. Participants were imaged before and after receiving an oral dosage of 20 milligrams of methylphenidate and a placebo. The PET-FDG scans showed a significant increase in regional brain glucose utilization when subjects performed the cognitive task, but the increases were greater when they did the task while on placebo as opposed to when they did the task while on methylphenidate. The increases in brain glucose metabolism induced by the task were almost 50% lower when they were performed with methylphenidate than with the placebo. In contrast, when methylphenidate was given when no cognitive task was being performed, brain glucose utilization did not change, indicating that its effects are dependent on the context of administration.

“The brain uses glucose as the main source of energy and increases its utilization in proportion to the level of activity. Therefore, the decrease in the amount of glucose required by the brain to perform the cognitive task with methylphenidate suggests that one of methylphenidate’s mechanisms is to make the brain more efficient,” said Volkow.

The researchers noted that in those individuals who performed well without the stimulant, methylphenidate improved performance, whereas in those who performed poorly while using a placebo, their performance deteriorated further when receiving the drug.

“The data suggest that the effects of methylphenidate are dependent on the individual’s performance and, since people take these medications in order to improve performance, they need to recognize that, for some, performance will deteriorate,” said Volkow.

In addition, “While methylphenidate increased some participants’ ability to focus on a task, use of stimulant medications outside of their intended clinical applications could result not only in deterioration of performance but also in addiction.”

PET Detects ‘Silent Heart’ Stage of Disease in Diabetics
As many as 50% of all cardiac deaths due to disease in the heart’s vessels occur in individuals with no prior history or symptoms of heart disease. In addition, standard coronary risk factors may fail to explain up to 50% of cardiovascular events. Now, researchers using PET are able to see changes in coronary blood vessels, offering hope that those at risk can receive earlier treatment and prolong life.

“Assessment of standard coronary risk factors such as arterial hypertension, smoking, hypercholesterolemia, or diabetes appears to be limited in defining an individual’s future cardiac risk,” said Thomas Schindler, MD, chief of nuclear cardiology at the University Hospitals of Geneva in Switzerland.

Early stages of atherosclerosis can be detected by different cardiovascular imaging techniques, he explained. For example, intravascular ultrasound may identify abnormal thickening of the subintimal space (below the inner layer of blood vessels) of the carotid artery as an early sign of developing arterial disease. Also, electron beam or multidetector CT (MDCT) may identify calcification of the heart vessels, and PET may detect functional abnormalities of the coronary arteries by unmasking mild reductions in the blood flow supply to the heart during stress testing.

Notably, the identification of abnormal thickening of the carotid arterial wall with intravascular ultrasound, coronary artery calcifications with MDCT, and functional abnormalities of the coronary circulation with PET have all been shown to identify the initiation and development of atherosclerotic disease of the heart vessels and future cardiovascular events such as myocardial infarction, sudden cardiac death, heart failure, or the need for revascularization procedures.

“These measures to detect clinically silent heart vessel disease may be more useful in defining the future cardiac risk in individuals than conventional coronary risk factor assessment and could thereby better reinforce the preventive therapy for improving the long-term cardiovascular outcome,” said Schindler.

The difficulty is that it is unknown which marker of subclinical heart vessel disease is first to manifest.

In a study of 68 asymptomatic individuals with adult onset diabetes, researchers were able to determine the concurrent prevalence of the thickening in arterial walls—carotid-intima media thickness (IMT), coronary artery calcification (CAC), and functional abnormalities of the coronary circulation (coronary vascular dysfunction). In these patients, all of whom had coronary vascular dysfunction as determined by PET scans, a 56% increase in the prevalence of abnormal carotid IMT was found, while 66% also had evidence of CAC.

The results showed that when PET revealed coronary vascular dysfunction as a functional precursor of coronary artery disease, these findings were not necessarily accompanied by abnormal increases in the carotid IMT or CAC, leading researchers to believe that the dysfunction may precede structural alterations of the arterial wall.

“PET assessment of functional abnormalities of the coronary circulation therefore may allow the earliest identification of developing heart vessel disease. This could lead to an optimized identification of the very early stage of the development of coronary artery disease, allowing physicians to initiate and/or reinforce preventive medical therapy strategies in order to improve the long-term cardiovascular outcome in these individuals at risk for heart disease,” said Schindler.