The long-term objective of this work is to contribute to basic research and pre-clinical applications of radiochemistry for better understanding of response assessment, molecular and physiological profiling, cell tracking and cell surface targeting in a comprehensive cancer center. The requested instrument will allow the efficient production of an assortment of fluorine-18 labeled radiotracers for pre-clinical investigations. These will leverage an already substantial investment of the Moffitt into imaging research, which has recently included the build out of a research radiochemistry laboratory adjacent to the cyclotron. Priority is assigned to tracers of highest interest to 8 major users with existing NIH supported programs that investigate novel therapeutic targets, or therapy response biomarkers in cancer. In the initial period of use, 18F-FAC;18F-FHBG and 18F-FMAU will be generated with this system, as these radiotracers have previously been synthesized on the Modular Lab system and spec sheets are available. Following QA/QC and signoff of the instrument, two routes for peptide radiolabeling will be pursued: 18F-NPFP for RGD (Arg-Gly-Asp);and 18F-SFB to label pHLIP (pH low insertion peptide), MTI-101 (developed in house to bind Hyd-1), and MTI-T02 (developed in house to bind TLR-2). After these, there are plans to pursue 18F Nifene (binds Nicotinic ?4?2 receptor), [18F] - FASu (substrate for Glu/Cys transporter SLC7A11) and 18F-CMD (substrate for indoleamine di-oxygenase, IDO) will be explored. Because of the variety and number of these tracers to be made within limited space, a small footprint robotic synthesis system is needed. The instrument will be managed as a shared service within the Small Animal Imaging core facility, which will be responsible for establishing recharge rates. Major user programs are supported by 10 R01, 1 U10, 1 U54, 1 P01 and 1 P50 grant. Long term support for this enterprise is provided by the Institution, which will cover the costs of the annual maintenance agreement apart from the facility's operating budget. Additional tracers, and developing programs will be supported as resources permit, and support and education will be extended to benefit the wider research and care community. These tracers will benefit cancer patients with improved, personalized knowledge of their disease, and from improved monitoring and prediction of treatment effects.

Public Health Relevance

A new instrument is requested to use in pre-clinical cancer research. The instrument enables robotic creation of fluorine-18 labeled radiotracer for PET scanning to safely show and measure key processes including cell proliferation, angiogenesis, targeted receptor binding, substrate metabolism, and pH imaging variety in the animal model. This robotic system enables custom synthetic processes to be assembled from a diverse set of modules, and enables us to have the flexibility to configure syntheses for novel PET tracers in pre-clinical cancer research.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1)
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Birken, Steven
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H. Lee Moffitt Cancer Center & Research Institute
United States
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Huang, Xuan; Pan, Zhongjie; Doligalski, Michael L et al. (2017) Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging. Oncotarget 8:46900-46914