eases , so improved understandings of HDAC expression and function could help in developing new treatments to improve patient health .
The Science Translational Medicine study was a significant step forward in achieving such understandings . Using [ 11 C ] Martinostat , the researchers performed PET scans of the brains of eight healthy human subjects and found characteristic patterns of uptake — reflecting HDAC expression levels — that were consistent among the subjects . This demonstrated the utility of the tracer and humans and opened the door to further application .
“ HDAC dysregulation has been implicated in a growing number of brain diseases , so being able to study HDAC regulation both in the normal brain and through the progression of disease should help us better understand disease processes ,” said Hooker . “ We ’ ve now started studies of patients with several neurologic or psychiatric disorders , and I believe Martinostat will help us understand the different ways these conditions are manifested and provide new insights into potential therapies .”
Hsiao-Ying ( Monica ) Wey and Tonya Gilbert , both of the Martinos Center , are the co-lead authors of the Science Translational Medicine paper . Additional authors include the Center ’ s Nicole Zürcher , Anisha Bhanot , Brendan Taillon , Fredrick Schroeder and Changning Wang .
Advancing PET Imaging With Quantitative Methods
One of the newest senior faculty members in the Center , Julie Price brings to the Martinos community a wealth of experience with quantitative positron emission tomography ( PET ). In a recent conversation she described her work and how it can benefit applications both in the lab and in the clinic .
What is quantitative PET ?
“ PET is an in vivo imaging modality that detects positron-emitting radiotracers with high detection sensitivity ( nanomolar concentrations ). When I say quantitative PET , I mean that we study the dynamics of the PET radiotracer in vivo to obtain absolute measurement of functional processes : the binding capacity of neuroreceptors , glucose metabolism , blood flow , enzyme activity , and more . We use pharmacokinetic modeling methods to do this .”
Why is this important ?
“ When you are developing a new radiotracer , for example , you want to make sure that your PET measurements are valid . Specificity and sensitivity studies help to ensure this ( e . g ., the radiotracer is binding to the receptor / target of interest and a measured change in the PET outcome is in fact reflective of change in the target ). Validation studies can be done in vitro and in animals but must also be done in humans . PET pharmacokinetic modeling helps us to do this .”
Where has the technique proved especially helpful ?
“ The validation of amyloid-beta plaque tracers included quantitative PET modeling studies that pro-
Photo by Caroline Magnain
vided a firm basis for routine PET amyloid imaging in Alzheimer ’ s disease ( AD ). This fueled a new era of AD imaging research and diagnostic criteria for AD were revised to incorporate the use of neuroimaging biomarkers . The whole idea is to detect as early as possible those individuals who might be on the path for AD neurodegeneration and identify those who would most benefit from therapeutic intervention .”