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Notebook — Society of Nuclear Medicine Editor’s Note: These reports are based on press information provided at the 53rd annual meeting of the Society of Nuclear Medicine held June 3 to 7 in San Diego. Is Being Overweight All in the
Brain? “From our molecular imaging research, we have discovered that overweight people have more of a certain type of serotonin receptor—the 5-HT2A receptor—in their brains,” said David Erritzoe, research fellow with the Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging in Copenhagen, Denmark. Serotonin is a chemical compound in the brain involved in the regulation of many functions, including appetite, sleep, and emotions, he added. “This relationship suggests that the 5-HT2A receptor is crucially involved in regulation of body weight and that the receptor should be exploited as a target for regulation of appetite.” Erritzoe is coauthor of “Overweight Associated With Increased Serotonin 2A Receptor Binding in Humans,” the first study to examine links between the 5-HT2A receptor and body weight. Obesity among adults has risen significantly in the United States—cutting across age, racial, and ethnic groups, and genders. Reports indicate that approximately 30%—or 60 million—of U.S. adults aged 20 and older are obese, and the percentages of obese young people and children have risen considerably as well. These increasing rates have profound implications for health because being overweight or obese increases the risk of coronary heart disease, high blood pressure, diabetes, stroke, and some cancers. “This is the first study where a large number of healthy individuals have been studied to determine the association between 5-HT2A and body weight,” said Erritzoe. “We found that a high body mass index [BMI] is associated with a high density of the 5-HT2A receptor in several brain regions—suggesting that overweight people have an upregulation [increase] of their brain 5-HT2A receptors. A number of drugs that block the 5-HT2A receptor are associated with weight gain; at the same time, studies in animals suggest that stimulation of the 5-HT2A receptor induces weight loss. Together, these findings point at a central role for the 5-HT2A receptor in the regulation of body weight.” Serotonin is a molecule synthesized by specific brain
cells (neurons), and it serves as a messenger molecule between neurons,
a so-called neurotransmitter, explained Erritzoe. It is released by
one neuron and received by receptors sitting on another neuron. Abnormalities
in serotonin’s transmitter system play an important role in many
disorders, including the biochemistry of depression, migraine, bipolar
disorder, anxiety, and eating disorders. “Our study deals with only moderately overweight people,” said Erritzoe, who explained that investigation should continue on whether 5-HT2A receptors are also involved in extreme underweight or overweight people. “An interventional study where people are investigated before and after an intended weight loss would reveal whether the 5-HT2A receptor binding can be modified through weight loss. In addition, trials involving different drug treatments aimed at the 5-HT2A receptor could reveal whether weight loss could be achieved through pharmacological effects on the receptor.”
“The degree of uptake of FDG usually corresponds to the severity of infection at the site,” said Wichana Chamroonrat, MD, a research fellow at the Hospital of the University of Pennsylvania (HUP) in Philadelphia. Chamroonrat and colleagues at HUP and The Children’s Hospital of Philadelphia (CHOP) performed the research reported at the annual meeting of the Society of Nuclear Medicine in San Diego last month. “Our findings show that FDG-PET should be employed as a study of choice for diagnosing chronic osteomyelitis,” said Chamroonrat, coauthor of “FDG-PET Is Highly Accurate for the Diagnosis of Chronic Osteomyelitis.” “Recent studies have shown that FDG-PET can be used in the evaluation of a variety of inflammatory and infectious processes, and we extended the use of this noninvasive scanning technique in our study.” Osteomyelitis, usually caused by bacteria, occurs most commonly in young children and older adults, but all age groups are at risk, said Chamroonrat. It may be caused by a variety of situations, including an infection from elsewhere in the body, an injury to a bone (an open fracture), or a minor trauma or bacteria in the bloodstream. If osteomyelitis, which affects approximately two of every 10,000 people, is not treated successfully, it may develop into chronic osteomyelitis, a persistent, painful infection that is very difficult to eliminate and may lead to loss of bone tissue, according to Chamroonrat. “Accurate diagnosis or exclusion of chronic osteomyelitis will substantially decrease the time required for starting appropriate treatments for these patients,” Chamroonrat said. Chamroonrat noted that FDG-PET is used relatively infrequently for detecting infection compared with its widespread applications in cancer management. In the study, researchers used FDG-PET imaging with 57 patients with suspected osteomyelitis, comparing scanning images with their final diagnosis based on surgical findings, microbiology, and clinical follow-up. “FDG-PET images allowed physicians to correctly diagnose the presence or absence of osteomyelitis in 53 of 57 patients,” she said, as well as in 26 of 27 patients with chronic osteomyelitis. FDG-PET had a 93% accuracy rate in the evaluation of osteomyelitis. Chamroonrat indicated that University of Pennsylvania researchers began studies examining FDG-PET and its use with infection and inflammation in the 1990s and credited the pioneering work of Hongming Zhuang, MD, PhD, of CHOP and Abass Alavi, MD, of the University of Pennsylvania. “Our researchers have shown that this powerful imaging modality is very successful in helping patients with a variety of diseases that are caused by bacteria and other organisms,” Chamroonrat said. “Our data show that the role of FDG-PET imaging in detecting and characterizing infection and inflammation is quite clear at this time. However, research in our own laboratory, as well as in other centers around the world should refine the criteria for optimal utilization of this modality in settings such as diabetic foot, infected prosthesis, and other complicated clinical scenarios.”
“The specificity of bone scintigraphy—or bone scanning—is enhanced by combining SPECT with spiral CT,” said Wolfgang Römer, MD, assistant professor and vice chair of the Clinic of Nuclear Medicine at the University of Erlangen/Nuremberg in Germany. “Because of this technology, the diagnostic process is shortened, reducing stress considerably for individuals waiting for a definite diagnosis.” Römer is coauthor of the study “Diagnostic Value of Tc-99m-DPD-SPECT/Spiral-CT Hybrid Imaging in Unclear Foci of Increased Bone Metabolism in Cancer Patients.” “With SPECT/CT, the morphologic correlate [form and structure] can be visualized to further clarify findings on bone scintigraphy,” Römer said. “We call our procedure ‘SPECT-guided CT.’ From our study, we conclude that SPECT-guided CT is able to clarify more than 90% of findings that were classified as indeterminate in the analysis of SPECT alone. That could mean that in daily clinical practice, additional radiological examinations can be avoided in 90% of patients with indeterminate findings in bone scintigraphy.” The researchers also significantly reduced the CT radiation exposure, according to the study, which Römer calls the first report on the benefit of SPECT/spiral CT in bone scintigraphy. The combination of SPECT and CT was introduced approximately five years ago but provided non–diagnostic-quality CT images, according to Römer. “The recently introduced combination of SPECT and spiral CT scanners enables combined SPECT/CT images, which are diagnostic,” he detailed. “With bone scintigraphy alone, it is not possible to differentiate bone metastases from benign processes causing enhanced bone metabolism.” Consequently, additional radiological examinations are regularly recommended to study the metabolic changes. These studies are performed separately and—most often—with a certain time delay. In addition, a radiologist analyzing the separate CT examination may not have detailed information on the scintigraphic findings. Römer cautioned that additional studies with larger patient populations are needed to carefully address the cost efficiency of this new technology and assess its value in a clinical setting.
“A new treatment protocol combining radionuclide therapy and chemotherapy may represent a distinct advantage over conventional protocols, especially when patients have metastatic prostate cancer that is not responding to hormonal therapy,” said Giuliano Mariani, MD, professor of nuclear medicine and director at the Regional Center of Nuclear Medicine at the University of Pisa Medical School. “Radionuclide therapy alleviated bone pain, but preliminary observations indicated that—if adequately combined with chemotherapy—it might produce clinical benefit in terms of regression and prolonged survival.” All men are at risk of developing cancer in the prostate. Prostate cancer occurs when the cells of the prostate begin to grow uncontrollably, and these cells may metastasize from the prostate to other parts of the body, especially the bones and lymph nodes, said Mariani. Approximately 234,000 men in the United States will be diagnosed with prostate cancer this year, and more than 27,000 will die of the disease, making it the second-leading cause of cancer death in men. “We explored combining radionuclide therapy based on the radioisotope Samarium-153 with carrier EDTMP and chemotherapy to achieve actual regression and prolonged survival,” said Mariani. “Our research confirms the possibility of achieving tumor targeting of a radiopharmaceutical with such efficiency that it induces a definite therapeutic effect, and this shows the possibility of obtaining a synergistic therapeutic effect in combination with conventional chemotherapy.” Mariani noted that increased blood toxicity is a major concern when combining radionuclide and chemotherapy, often limiting clinical use of such protocols. He considers it encouraging that this research did not show an increased effect. “The blood toxic effects of our combination regimen were mild and comparable to those observed when the two therapies were used separately,” Mariani said. “We are now evaluating our patients with an extended follow-up in order to assess the effect of the combined protocol on survival. Future investigations should explore the possibility of employing higher doses of the radiopharmaceutical in order to achieve the highest possible therapeutic effect—with the lowest possible toxic effect.”
“We have found that labeling the antibody CD45 with the alpha-emitter Bi-213 breaks resistance to radiation therapy and chemotherapy in leukemia cells by overcoming DNA-repair, which plays an important role in resistance,” said Claudia Friesen, PhD, group leader of the laboratory of molecular biology in the nuclear medicine department at the University Ulm in Germany. “We provided the molecular requirements for overcoming this resistance and for alpha particles—induced cell killing.” Friesen noted that the targeted alpha particle radioimmunotherapy increases the dose to leukemia cells by two orders of magnitude, killing single-targeted leukemia cells while sparing nontarget tissues from detrimental radiation effects. “The targeted alpha particle therapy is much more potent than targeted beta particle therapy or external radiation therapy,” Friesen said. Low doses of alpha particles cause a prompt and complete cell kill in sensitive and resistant tumor cells, researchers discovered. “Our work considerably expands therapeutic options for therapeutically applied radionuclides,” she added. “This technique will have a wide application in many solid tumors, using suitable peptides as carriers of alpha-emitting radionuclides. “Understanding the molecular mechanisms of sensitivity and/or resistance of tumor cells to radiation and chemotherapeutic drugs is crucial and fundamental for the development of novel treatment options in leukemia and solid tumor therapy. It provides the foundation for the discovery of novel anticancer compounds and the development of methods to sensitize previously resistant tumor cells to anticancer therapy,” said Friesen, who noted that the first clinical trial will begin soon. Leukemia affects women, men, and children of all ages. The disease starts in the bone marrow but usually spreads quickly into the blood. Over time, it may spread to the lymph nodes, spleen, liver, covering of the brain and spinal cord, spinal fluid, and other organs. Approximately 35,000 individuals will be diagnosed with leukemia this year in the United States, and nearly 23,000 individuals die annually from the disease. “New options are needed to improve therapeutic
success in the treatment of cancer, especially since tumors’ resistance
to chemotherapy or radiation therapy is one of the primary causes of
failure in treating the disease,” Friesen said. “Attempts
to improve the results of chemotherapy and radiotherapy by increasing
the total radiation absorbed dose, by increasing the concentration of
chemotherapeutic drugs or by changing chemotherapeutic drugs have been
only partially successful.”
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July
17, 2006
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