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For other articles and previous issues click here. August 8, 2005 Greetings
From Toronto! Editor’s note: This summer’s Society of Nuclear Medicine meeting in Toronto brought together thousands of scientists, clinicians, and technologists from around the world. This article contains research highlights from the meeting provided by the society. Studies Report Radioimmunotherapy
Promise “Nuclear medicine has a growing role in treating non-Hodgkin’s lymphoma,” said Richard L. Wahl, MD, director of nuclear medicine/PET at Johns Hopkins University Medical School’s department of radiology. “When nuclear medicine is used earlier in the course of the illness, there is a higher efficacy of treatment.” Wahl presented nearly eight-year follow-up results from patients who received radioimmunotherapy (RIT) with Bexxar (Tositumomab and Iodine I-131 Tositumomab) to treat non-Hodgkins lymphoma. The findings from the study “An Update of Complete Response Durability Following Tositumomab and Iodine I-131 Tositumomab (the Bexxar Therapeutic Regimen) in a Pivotal Study of Patients (PTS) Refractory to Their Last Chemotherapy” suggest “that we may have changed the course of the disease,” said Wahl. In 2001, Wahl reported up to 47-month follow-up on 60 patients who had received RIT with Bexxar after they had failed to respond or responded poorly to multiple types of chemotherapy. Sixty-five percent of those responded to treatment; 20% had complete response, or no evidence of remaining cancer nearly four years after treatment. The update presented at this year’s SNM meeting revealed that those patients who achieved a “complete response” four years earlier showed no recurrence after eight years. “We have achieved an impressive response rate from a single dose of therapy,” said Wahl. “We can adjust the dose, depending on how it behaves in a person.” The current standard course of treatment for non-Hodgkin’s lymphoma is intensive chemotherapy. Patients receive chemotherapy every three weeks over a time period of up to six months. Good results from the initial Bexxar studies have prompted investigation into using RIT in initial therapy instead of a refractory treatment. “An Update of Complete Response Durability Following Tositumomab and Iodine I-131 Tositumomab (the Bexxar Therapeutic Regimen) in a Pivotal Study of Patients (PTS) Refractory to Their Last Chemotherapy” was written by Wahl; C. Divgi, nuclear medicine/clinical immunology, Memorial Sloan-Kettering Cancer Center, New York; S. J. Goldsmith, department of radiology/nuclear medicine, Weill Medical College of Cornell University, New York; S. M. Kroll, Biostatistics, Corixa Corp., San Francisco; and M. S. Kaminski, division of hematology/oncology, University of Michigan Health System, Ann Arbor. Fractionated RIT “Fractionated radioimmunotherapy is feasible and our data suggest better safety results than bolus RIT, since patients appear to tolerate higher doses of therapy,” said Jean-François Chatal, MD, of the Institut de Biologie, INSERM, in Nantes, France. “Such radioimmunotherapy methods and reagents should expand the opportunities for the therapy of blood-type cancers and encourage our pursuit of this nuclear medicine technology for the treatment of more therapy-resistant solid cancer. This multicenter trial is also evaluating the safety and efficacy of this agent in a continuing dose-escalation trial.” Investigators used a specific antibody—DOTA-Conjugated, Humanized Anti-CD22 Epratuzumab—which mainly consists of human material, to carry radioactive yttrium-90 to the lymphoma cells in 21 patients. The study, “Fractionated Radioimmunotherapy in NHL With DOTA-Conjugated, Humanized Anti-CD22 Epratuzumab at High Cumulative 90Y Doses,” followed the RIT patients in part to determine whether a higher total radiation dose delivered during several treatments can be used to safely improve treatment response. Chatal’s coauthors in the study are J.-L. Harousseau, Service d’Hematologie, Centre Hospitalier Universitaire, Nantes, France; F. Griesinger and J. Meller, Georg August University, Göttingen, Germany; M. Pfreundschuh and C. M. Kirsch, Saarland University Medical School, Homburg/Saar, Germany; R. Naumann and J. Kropp, University Hospital Dresden, Dresden, Germany; D. Huglo and F. Morschhauser, Centre Hospitalier Régional Universitaire de Lille, Lille, France; J. Lateiner, W. A. Wegener, I. D. Horak, and D. M. Goldenberg, Immunomedics Inc, Morris Plains, N.J. PET Imaging Investigating
Link Between Obesity and Heart Functioning “The increasing prevalence of obesity in the United States is of considerable public health concern, and the mechanisms by which obesity initiates and accelerates vascular disease are still poorly understood,” said Thomas H. Schindler, MD, from UCLA’s School of Medicine, who presented on the topic at the 52nd annual meeting of the Society of Nuclear Medicine held in Toronto this past June. “Quantitative PET imaging—with the assessment of the functional stage of the heart vessels—may indeed provide important information to stratify [or classify] the risk of an individual for future cardiovascular events.” Schindler cowrote the study “Obesity Is Associated With an Impairment of Coronary Circulatory Function.” The researchers measured myocardial blood flow responses to cold pressor testing with N-13 ammonia and PET. They studied 71 patients grouped by body mass. Schindler told attendees that PET imaging may identify overweight/obese individuals with normal SPECT imaging results who are still at increased risk for the progression of coronary artery disease and future cardiovascular events. “In overweight/obese individuals, normal cardiac single photon emission computed tomography [SPECT] imaging—which widely excludes hemodynamically obstructive coronary heart disease—and quantitative PET imaging may identify an early functional impairment of the heart vessels that may precede morphological changes in the further course of the development of coronary artery disease,” Schindler said. Schindler’s coauthors of “Obesity Is Associated With an Impairment of Coronary Circulatory Function” are Jerson Cadenas, Michael Kreissl, Xiao-Li Zhang, and Heinrich R. Schelbert, all of the department of molecular and medical pharmacology at UCLA’s David Geffen School of Medicine. PET May Assess Chemotherapy
Response “PET might be a promising tool for early prediction of response to chemotherapy and to individualize treatment for patients,” said Norbert Avril, MD, chief of the division of nuclear medicine at the University of Pittsburgh Medical Center. “The development of new methods that allow earlier monitoring of response to treatment is highly relevant in the current clinical setting… It is important to identify response to therapy as early as possible so that ineffective therapies can be discontinued. Patients who are not responding to a given chemotherapy are not only suffering from unnecessary side effects but might be offered potentially more effective treatments.” FDG-PET can identify primary ovarian cancer and tumor spread in the pelvis and abdominal cavity by visualizing the increased metabolic activity of cancer cells. The researchers found that there is little or no decrease in the metabolic activity of nonresponding tumors, but there is a significant decrease in glucose metabolism in responding tumors after the first cycle of chemotherapy. “Computed tomography [CT] and magnetic resonance imaging [MRI] are typically used to evaluate response to chemotherapy,” Avril said. “The decrease in tumor size is the most important criterion to assess if chemotherapy was successful. Both imaging modalities, CT and MRI, have certain limitations in imaging tumor sites in the abdomen and pelvis. More important, several cycles of chemotherapy are generally necessary before the tumor size changes and physicians know if the treatment was successful.” The researchers used FDG-PET scans to measure tumor activity before neoadjuvant chemotherapy and after the first and third courses of chemotherapy in 33 patients. They found a significant increase in survival among patients who the PET scan showed had responded to the first course of treatment. The overall survival of these “metabolic responders” to the first chemotherapy treatment was 38.3 months compared with 23.1 months for the nonresponders. There was a similar significant survival increase among who responded after the third course of chemotherapy. The results suggest that sequential FDG-PET could be used to predict response to neoadjuvant chemotherapy in advanced stage ovarian cancer as early as after the first cycle of chemotherapy, which Avril noted would be significantly sooner than with current CT or MRI. Avril noted that the 33-patient study needs a larger, prospective follow-up study to confirm the findings. He and his colleagues conducted the study at the Technical University of Munich, Germany. The title of the report is “Sequential FDG-PET for Prediction of Survival Following Neoadjuvant Chemotherapy in Advanced Ovarian Cancer.” “This research highlights an important trend in PET,” said Lale Kostakoglu, MD, an associate professor at Cornell University’s Weill Medical School. “This team of researchers from Munich used PET not just for diagnosis or staging of ovarian cancer, but for prognosis.” Three-Modality Research
Scanner Offers Flexibility “For years, researchers have been taking clinical imaging systems and retrofitting them so they could be used to image animals, and this approach has limitations,” said Bradley E. Patt, PhD, president and CEO of Gamma Medica, of Northridge, Calif. “Combining anatomical computed tomography [CT] imaging with the functional positron emission tomography [PET] and single photon emission computed tomography [SPECT] imaging in one instrument gives researchers a revolutionary set of imaging tools in one seamless system. Researchers can choose the modalities that best fit their research goals.” With the Gamma Medica imaging system, researchers will be able to use PET only, CT only, PET with CT, SPECT with CT, or all three, according to Patt. PET May Help Predict Lung
Disease After Trauma “Acute respiratory distress syndrome [ARDS] may be identifiable prior to its clinical presentation by diffuse lung uptake on FDG-PET scans,” said Kathryn A. Morton, MD, professor of radiology at the University of Utah in Salt Lake City. “This would identify patients who may benefit from aggressive immune modulation therapy.” ARDS is a life-threatening condition in which inflammation of the lungs and accumulation of fluid in the air sacs leads to low blood oxygen levels; it can be caused by any major lung inflammation or injury (pneumonia, septic shock, trauma, aspiration of vomit, or chemical inhalation). ARDS usually develops within 24 to 48 hours of an injury or illness, and the duration and intensity of the condition can vary considerably from patient to patient. Approximately 15% to 30% of trauma patients develop ARDS, which Morton said may be caused by an exaggerated immune response leading to systemic inflammation. Its mortality rate ranges from 35% to 50%. The pilot study followed eight major trauma patients. By evaluating the FDG uptake in the lungs, researchers found that all four patients who showed diffuse uptake of FDG in the lungs progressed to ARDS within five days. None of the four patients with focal uptake developed ARDS. “Aggressive immune modulation therapy may prevent ARDS if vulnerable patients could be identified in advance. FDG uptake has been reported to occur in areas of inflammation,” Morton said, also noting that the study’s results need to be confirmed in a larger series of patients. Morton’s coauthors for “FDG-PET May Predict Development of ARDS in Trauma Patients” are Paige B. Clark, MD, radiology, Wake Forest University, Winston-Salem, N.C., and Preston Miller, MD, surgery, Wake Forest University. |
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