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Title: The Michigan New Technology Training and Research (MNTR) Translational Program in Nuclear Medicine (Final Report)

Technical Report ·
DOI:https://doi.org/10.2172/1482557· OSTI ID:1482557

The Michigan New Technology Training and Research (MNTR) Translational Program in Nuclear Medicine and Molecular Imaging This project established the Michigan New Technology Training and Research (MNTR) translational program, focused on the acceleration of new clinical molecular imaging methods. Molecular imaging approaches to imaging are a very flexible and powerful development, with many recent examples advancing the diagnosis and guiding the management of human disease. These methods depend on the design, synthesis and testing of new radiotracers (molecules designed to target specific cells or tissues in the body), labeled with short-lived radioactive atoms (positron emitters). The new radiotracers are imaged in the human body using positron emission tomography (PET) imaging. The University of Michigan PET Center has considerable experience in the discovery, development, refinement and initial human applications of new PET radiotracers. An emerging impediment to efficient availability of new PET radiotracers, however, involves the regulatory environment at multiple levels. Many potentially successful ideas are delayed or even prevented from entering human use by these barriers. In the current grant, we provided hands-on experience for the next generation of young scientists working in molecular imaging so that they are equipped to effectively move new ideas and radiotracers from the research laboratory to the nuclear medicine clinic (bench-to-bedside). For new radiotracer development, oversight by the Food and Drug Administration (FDA), the Nuclear Regulatory Commission (NRC), and local institutional committees and reviews are required. These aspects of translation from laboratory to clinic are often omitted from the formal training of new scientists, but were provided to three trainees via direct mentorship in the MNTR program. The MNTR training program built on the translational successes of the University of Michigan Division of Nuclear Medicine and capitalized on our strengths (facilities, faculty, a wide-ranging selection of projects, and the experience and commitment to bring new radiotracers into human studies) to systematically train three fellows in radiochemistry and nuclear medicine. Integrated training in development, validation and clinical translation of new PET radiotracers occurred through practical involvement in multiple research projects, each at a different stage along the pathway from bench-to-bedside. Each trainee obtained experience of the entire process over about 2 years. Projects involved development of new radiotracers for neurodegenerative disorders (e.g. Alzheimer disease), movement disorders (e.g. Parkinson disease, progressive supranuclear palsy) and neurodevelopmental syndromes (e.g. Tourette syndrome) as well as new radiochemistry methods for synthesizing radiotracers. Each project was pursued in a close collaboration between the fellow trainee and both the clinical and basic science faculty at the University of Michigan PET Center, and provided an unprecedented opportunity for the highest-level training in academic radiochemistry and nuclear medicine research. The project has resulted in 17 peer-reviewed publications to date, and at least 4 more are in preparation. Additionally, 1 book chapter and 26 conference presentations have resulted from this grant. Upon completion of the MNTR Program, the trainees have emerged as translational scientists wielding the necessary skill-set (practical research experience, multidisciplinary training, regulatory know-how) to embark on successful careers in translational molecular imaging, bringing continued advances in the field to bear on important human disorders. As a metric of the Program’s success, one fellow has already secured employment in the field, while the other two are finishing writing papers; they wish to also stay in the radiochemistry and nuclear medicine community, and are currently applying for jobs.

Research Organization:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
DOE Contract Number:
SC0012484
OSTI ID:
1482557
Report Number(s):
DOE-UMICH-12484
Country of Publication:
United States
Language:
English

References (17)

Development of Customized [18F]Fluoride Elution Techniques for the Enhancement of Copper-Mediated Late-Stage Radiofluorination journal March 2017
Synthesis of Diverse 11 C-Labeled PET Radiotracers via Direct Incorporation of [ 11 C]CO 2 journal April 2016
Identification of [ 18 F]TRACK, a Fluorine-18-Labeled Tropomyosin Receptor Kinase (Trk) Inhibitor for PET Imaging journal January 2018
Cu-Mediated C–H 18 F-Fluorination of Electron-Rich (Hetero)arenes journal June 2017
Copper-Mediated Radiofluorination of Arylstannanes with [ 18 F]KF journal October 2016
Gallium-68: methodology and novel radiotracers for positron emission tomography (2012–2017) journal September 2018
Radiochemistry, PET Imaging, and the Internet of Chemical Things journal August 2016
Synthesis and Initial In Vivo Evaluation of [11C]AZ683 – a Novel PET Radiotracer for Colony Stimulating Factor 1 Receptor (CSF1R) preprint November 2018
Equipment and Instrumentation for Radiopharmaceutical Chemistry book April 2019
Fluorine-18 patents (2009–2015). Part 2: new radiochemistry journal September 2016
Automated synthesis of [ 68 Ga]oxine, improved preparation of 68 Ga-labeled erythrocytes for blood-pool imaging, and preclinical evaluation in rodents journal January 2018
A Kinome-Wide Selective Radiolabeled TrkB/C Inhibitor for in Vitro and in Vivo Neuroimaging: Synthesis, Preclinical Evaluation, and First-in-Human journal July 2017
Fluorine-18 patents (2009–2015). Part 1: novel radiotracers journal January 2016
Clinical Applications of Radiolabeled Peptides for PET journal September 2017
Synthesis of [ 18 F]Arenes via the Copper-Mediated [ 18 F]Fluorination of Boronic Acids journal November 2015
An updated radiosynthesis of [18F]AV1451 for tau PET imaging journal June 2017
Automated synthesis of PET radiotracers by copper-mediated 18 F-fluorination of organoborons: Importance of the order of addition and competing protodeborylation
  • Mossine, Andrew V.; Brooks, Allen F.; Bernard-Gauthier, Vadim
  • Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 61, Issue 3 https://doi.org/10.1002/jlcr.3583
journal February 2018