Reporter's Notebook: News From SNMMI 2018
Vol. 19 No. 10 P. 6
Editor's Note: This article is based on press materials provided by SNMMI at its Annual Meeting in Philadelphia.
Novel PET Tracer Images Cardiovascular Infections
A PET tracer has been developed that can accurately image cardiovascular infections, which are extremely dangerous and have a high fatality rate. The research was presented at the SNMMI 2018 Annual Meeting.
"Early diagnosis is crucial for proper patient management, as early treatment can improve prognosis and patient outcome," according to Mirwais Wardak, PhD, at Stanford University School of Medicine in Stanford, California. "In the clinic right now, we really lack the tools to be able to specifically image bacterial infections. To address this problem, we developed a novel PET tracer called 6ʹʹ-[18F]Fluoromaltotriose, which is transported into bacterial cells by the maltodextrin transporter, a membrane transport system that is exclusive to bacteria and not present on mammalian cells. To our knowledge, this is the first time that a fluorine-18 based PET tracer specific to bacteria has been used to image bacterial infection of the heart."
For this study, the diagnostic accuracy of 6ʹʹ-[18F]Fluoromaltotriose PET/CT imaging was conducted in a Staphylococcus aureus–induced endocarditis mouse model.
"Endocarditis is an infection of the endocardium, which is the inner lining of the heart chambers and heart valves," Wardak said. "Staphylococci bacteria are the most common causing agents of endocarditis."
6′′-[18F]Fluoromaltotriose was able to image valvular infection with high sensitivity and specificity. Results showed an approximate 2.5-fold higher mean tracer uptake in the aortic valves of the infected mice when compared with the control mice.
"The results of this research overcome several fundamental limitations of current methods and promise to significantly impact the clinical management of patients suffering from infectious diseases of bacterial origin," Wardak said. "We believe that 6ʹʹ-[18F]Fluoromaltotriose PET/CT will play a vital role in the detection and monitoring of bacterial infection in patients, eg, as a result of cardiovascular infection, infection after surgery, medical device–related infections, fever of unknown origin, etc. We also believe that PET imaging with 6ʹʹ-[18F]Fluoromaltotriose will be helpful in the assessment of antibiotic therapy."
Plans are currently underway to have this PET radiotracer translated into the clinic. Looking ahead, Wardak and his colleagues also envision that 6ʹʹ-[18F]Fluoromaltotriose will be useful in other clinical settings beyond infectious disease: "For example, this tracer could be used to image the homing of bacteria against tumors and could, therefore, be used to monitor bacteria that have been trained to kill tumors, eg, Clostridium novyi engineered against glioblastoma cells."
New Technique May Help Tackle Brain Disease
A new molecular imaging method can monitor the success of gene therapy in all areas of the brain, potentially allowing physicians to more effectively treat brain conditions such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis. The research was presented at the SNMMI 2018 Annual Meeting.
Gene therapy for diseases of the central nervous system is a growing field; however, progress is limited by the absence of imaging techniques that can successfully monitor delivery of the therapy. Although reporter gene systems have been a key tool in molecular imaging for a number of years, they have not allowed monitoring of all areas of the brain. A new PET reporter gene/probe system makes it possible, for the first time, to noninvasively monitor the level and location of gene expression in all areas of the brain, giving the medical team an early indication of the likelihood of treatment success.
"It is challenging to find a reporter gene and imaging agent that can be used in all areas of the brain with a high signal-to-background ratio," according to Thomas Haywood, PhD, from the department of radiology at Stanford University in Stanford, California. "18F-DASA-23 is a novel radiotracer, or reporter probe, developed in the Gambhir Lab at Stanford, that is capable of crossing the blood-brain barrier and targeting the pyruvate kinase M2 (PKM2) protein in the central nervous system with minimal endogenous expression in the brain. This allows us to monitor reporter gene expression and, ultimately, therapeutic gene expression for gene therapy in all regions of the brain."
After validating the utility of PKM2 as a PET reporter gene, mice were infected with a virus containing the gene, then imaged with the 18F-DASA-23 radiotracer over a period of two months to observe the increase in PKM2 expression over time. Results, confirmed by 18F-DASA-23 uptake studies and messenger RNA analysis, showed a good correlation between PKM2 and the radiotracer. Further analysis showed an increase in PKM2 expression in infected mice when compared with controls. These encouraging data suggest PKM2 has the potential to be further developed into a PET reporter gene system for the imaging of gene therapy in the central nervous system. In addition, the radiotracer has recently undergone first-in-human trials at Stanford for the early detection of therapeutic response in glioblastoma.
"Having a reporter gene/reporter probe system that allows monitoring of all areas of the brain opens the door to more accurate and less invasive imaging of the brain and of gene therapies used to tackle diseases of the brain," Haywood said.