Researchers Identify Method to Stratify Breast Cancer Without Biopsy

Scientists from the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have discovered a possible way for malignant breast tumors to be identified, without the need for a biopsy. The findings were published online in the Journal of Nuclear Medicine.

Current imaging modalities miss approximately 30 percent of breast cancers and cannot distinguish malignant tumors from benign tumors and require invasive biopsies. Approximately 5.6 million biopsies performed in the United States find only benign lesions. These biopsies cause substantial stress for patients and have high costs.

“The challenge has been to develop an imaging agent that will target a specific, fingerprint biomarker that visualizes malignant breast lesions early and reliably,” says Mathew Thakur, PhD, professor of radiology at Jefferson Medical College of Thomas Jefferson University and director of radiopharmaceutical research and nuclear medicine research.

Dr. Thakur and colleagues studied an agent called 64Cu-TP3805, which is used to evaluate tumors via PET imaging. This agent detects breast cancer by finding a biomarker called VPAC1, which is overexpressed as the tumor develops.

Researchers compared the images using that agent with images using the “gold standard” imaging agent, 18F-FDG. They used MMTVneu mice, which are mice that develop breast tumors spontaneously, like humans. The mice first received a PET scan using the 18F-FDG, a CT scan and finally another PET scan using 64Cu-TP3805.

Ten tumors were detected on the mice. Four tumors were detected using both 18F-FDG and 64Cu-TP3805, and four additional tumors were found with 64Cu-TP3805 only. All eight tumors overexpressed the VPAC1 oncogene on tumor cells and were malignant by histology. The remaining two tumors were benign and were detected only with 18F-FDG. They did not express the VPAC1 oncogene, and were not detected by the 64Cu-TP3805.

“If this ability of 64Cu-TP3805 holds up in humans, then in the future, PET scans with 64Cu-TP3805 will significantly contribute to the management of breast cancer,” Dr. Thakur says.

— Thomas Jefferson University



PET Plays Critical Role in Supporting Parkinson’s Disease Research
A large-scale study to measure the effectiveness of dopamine cell transplantation in Parkinson’s disease patients shows significant improvements in motor skills and brain function, according to research in the Journal of Nuclear Medicine (JNM).

The results demonstrate that transplanted cells were viable and integrated well with the host brain tissue. Furthermore, these cells produced dopamine that helped support the brain and led to improved motor symptoms. These improvements were sustained over a four-year study period.

“This study provided new insights into the time course of transplantation outcome,” says David Eidelberg, MD, study co-author and director of the Neuroscience Center at the Feinstein Institute for Medical Research in Manhasset, N.Y. “Comprehensive long-term clinical follow-up, together with molecular imaging, allows for a more realistic appraisal of this kind of intervention for Parkinson’s disease.”

Researchers reported long-term clinical and imaging outcomes after transplantation from 33 patients who originally participated in a one-year, double-blind, placebo-controlled trial of embryonic dopaminergic cell implantation for Parkinson’s disease. Clinical improvement in motor ratings, as well as increased brain uptake of 18F-fluorodopa (18F-FDOPA) – the radiotracer investigates the function of dopamine grafts – was evident at one, two, and four years after the transplantation surgery.

The findings reported in this study demonstrate the critical roles of PET – a noninvasive molecular imaging technique – to screen patients for transplantation procedures and objectively assess long-term graft survival.

“This work provides a valuable template for conducting imaging-based trials of cell transplantation for Parkinson’s disease and perhaps other neurodegenerative disorders,” said Yilong Ma, PhD, lead author of the JNM study and associate investigator at the Feinstein Institute for Medical Research. “It offers guidance in the design of this type of trial, particularly with respect to the use of quantitative imaging as an adjunct to clinical assessments.”

According to the National Institute of Neurological Disorder and Stroke in Bethesda, Md., Parkinson’s disease belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms are tremor – or trembling in hands, arms, legs, jaw, and face; rigidity – stiffness of the limbs and trunk; bradykinesia –slow movement; and/or postural instability – impaired balance and coordination.

Parkinson’s disease usually affects people over 50. Early symptoms are subtle and occur gradually. In some people, the disease progresses more quickly. Parkinson’s disease is both chronic and progressive. Currently, there is no cure; however, medications provide dramatic symptom relief. Novel surgical interventions, such as cell transplantation and gene therapy, are being investigated for patients with medically refractory symptoms.

— Society of Nuclear Medicine



Using Telemedicine for ICU Patients Not Linked with Survival Rates

Remote monitoring of patients in intensive care units (ICUs) was not associated with an overall improvement in the risk of death or length of stay in the ICU or hospital, according to a study in JAMA.

Experts recommend that intensivists (intensive care physicians) care for ICU patients onsite because of an associated lower rate of illness and death. However, a shortage of intensivists has led to the use of telemedicine technology to allow intensivists to extend their reach by remotely and simultaneously caring for patients in several ICUs (ICU telemedicine [tele-ICU]), the authors write. “Remote monitoring may be a partial solution for the intensivist shortage, but it is expensive, its use is increasing, and there are few data in the peer-reviewed literature evaluating its effect on morbidity and mortality,” the authors add.

Eric J. Thomas, MD, MPH, of the University of Texas Health Science Center at Houston, and colleagues assessed tele-ICU intervention on mortality, complications, and length of stay (LOS) in six ICUs of five hospitals in a large U.S. healthcare system by measuring outcomes before and implementing tele-ICU. The study included 2,034 patients in the preintervention period (January 2003 to August 2005) and 2,108 patients in the postintervention period (July 2004 to July 2006).

Almost two-thirds of  patients in the postintervention group had physicians who chose minimal delegation to the tele-ICU (n = 1,393 [66.1 percent]), in which the tele-ICU intervened only for patients in life-threatening situations. Physicians delegated full treatment authority to the tele-ICU for 655 patients (31.1 percent).

The tele-ICU system included a remote office equipped with audiovisual monitoring and a computer workstation providing real-time vital signs with graphic trends; audiovisual connections to patients’ rooms; early warning signals regarding abnormalities in status; and access to imaging studies and the medication administration record. Tele-ICU physicians conducted rounds based on subjective assessments of illness severity.

The researchers found that the observed hospital mortality rates were 12 percent in the preintervention period and 9.9 percent in the postintervention period. After adjusting for severity of illness, there were no significant differences associated with the telemedicine intervention for hospital mortality. ICU mortality rates were 9.2 percent in the preintervention period and 7.8 percent in the postintervention period, with the difference also not significant after adjustment.
The observed average hospital LOS among patients who survived to discharge was 9.8 days preintervention and 10.7 days postintervention; the observed average ICU LOS for the patients who survived to transfer was 4.3 days for the preintervention period versus 4.6 days for the postintervention period, with neither difference significant.

“There was a significant interaction between the tele-ICU intervention and severity of illness, in which tele-ICU was associated with improved survival in sicker patients but with no improvement or worse outcomes in less sick patients,” the researchers write.

Implementing tele-ICU was not associated with reduced overall hospital mortality for patients in these six ICUs, according to the study. Also, the lack of apparent benefit may be attributed to low decisional authority granted to the tele-ICU and various effects across different types of patients. “Given the expense of tele-ICU technology, the conflicting evidence about its effectiveness, and the existence of other effective quality improvement interventions for ICUs, further use of this technology should proceed in the context of careful monitoring of patient outcomes and costs,” say the study authors.

— JAMA and Archives Journals