This application requests funding to support the purchase of carbon-11 automation equipment for human PET radiotracer production. The Massachusetts General Hospital's Athinoula A. Martinos Center for Biomedical Imaging was home to the first combined Magnetic Resonance Imaging (MRI)/Positron Emission Tomography (PET) human imaging system and now houses two MR-PET scanners as part of an imaging core that enables a broad community of users the ability to explore human neurochemical function and its relationship to disease. The scanners continue to be in high demand, with a large user base that has grown over the past seven years and comprises efforts from the departments of radiology, oncology, neurology and psychiatry. In fact, the facility boasts more than forty IRB-approved neuroscience protocols that use one or more of fifteen radiotracers approved for human use. Seven of these radiotracers are synthesized using carbon-11 and account for more than 80% of the MR-PET neuroscience research volume. The radiotracer production facility, which operates as a service core to its users, prepared approximately 300 human doses of carbon-11 radiotracer in 2016 per year for human use in addition to the hundreds of small animal and chemical research studies performed in that same year. Our success in building a user base has been particularly strong in the areas of neuroinflammation and neurotransmitter-neurovascular coupling research. At the same time, we are seeing new and rapidly growing communities of MR-PET users in the areas of epigenetics and neurodegeneration. Because of these, the demand for MR-PET imaging using carbon-11 has grown far beyond our volume capacity because of the limited number of automated systems that are capable of use with this isotope. The facility currently has a unit for producing [11C]methyl iodide from [11C]carbon dioxide (GE FXMeI) and another for converting the [11C]methyl iodide to a radiotracer, e.g. [11C]PBR28 (GE FXM). To help keep up with user demand, the radiotracer production facility staff has adapted an automated synthesizer designed for fluorine-18 labeling to work in the context of carbon-11. At this point, however, no options exist for further volume growth in carbon-11 radiotracer production for MR-PET imaging without the purchase of additional equipment. This issue is an especially pressing one given as currently only ~60% of the carbon-11 requests each month can be fulfilled. Staffing is sufficient within the facility to boost volume to nearly match the demand with the purchase and installation of a new double miniature hot cell housing a carbon-11 unit (FXMeI and FXM) for radiotracer preparation?the equipment for which we are seeking funding. The instrument upgrade enabled by the NIH shared grant mechanism will therefore play an integral role in supporting MR-PET imaging for investigators throughout the greater Boston research community, and thus in helping to solve a range of major neuroscience questions that we face. !
Radiotracers used in positron emission tomography (PET) enable scientists to measure chemical interactions in living human tissues like the brain that are otherwise inaccessible, with clear public health benefits deriving from improved understandings of, among other disorders, neurodegenerative diseases and mental illness. These radiotracers are prepared using radioactive elements like carbon-11, which has a half-life of only 20 minutes, and require sophisticated automation to handle the material safely and quickly. The proposed automated equipment will enable us to keep pace with the increasing demand for PET radiotracers for use in neuroscience research at the MGH Martinos Center for Biomedical Imaging and in the Greater Boston area. !
