Dr. Thomas Mangner
Dr. Mangner was the first member of the CHM PET Center team on site in 1993. He worked with the architechs in designing the radiochemistry laboratory and tackled many of the problems in getting a new center underway. These included ordering all equipment and supplies, setting up a database system for recording and organizing all data required by the FDA and the State of Michigan for radiation issues, and providing doses of FDG required for initial patient studies.
During the first year of operation, he designed and built a C-11 methyl iodide module (which was also used to produce C-11 acetate) and an alkylation module which allowed for the production and use of C-11 Flumazenil, hydroxyephedrine (HED) and a-methyl tryptophan (AMT) in human studies. Recognizing that the conventional methods of handling multiple O-15 water and N-13 ammonia doses resulted in excessive radiation exposure to the chemist, he designed and built a remote robot handling system which provided multiple bolus doses of these tracers with virtually no operator radiation exposure.
Over the years, he has tackled many tracer chemistry production problems by designing components and systems to overcome these problems. For example, the level of reliability that Dr. Pulak Chakraborty has achieved with the tracer C-11 AMT would not be possible without the following systems:
1) the overall module design which allows for the controlled introduction and removal of various reagents to the reaction mixture,
2) the heater/cooler reaction block which allows not only for controlled heating, but for maintaining minus 50°C for at least 45 min, necessary for the formation of the precursor anion,
3) the PEEK reaction cap which allows for the introduction of air- and moisture-sensitive lithium diisopropyl amide (LDA) as well as closed heating of reaction mixtures well above the boiling point of the solvent used, and
4) the method of producing small quantities of freshly-made LDA for each preparation using disposable components. The basic alkylation module design was used in the production of novel F-18 thymidine analogs, including F-18 FLT (with Drs Tony Shields and John Grierson) and in the introduction of novel chemistries associated with the development of F-18 FAU, FMAU, FBAU and FIAU.
In recent years, he has refined the basic alkylation module design to make it a universal PET tracer synthesis module (including use for F-18 FDG) and has developed a system for fully automated computer control, data archiving, and security access, making the new modules compatible with cGMP requirements. The first fully automated PET tracer synthesis using this module was C-11 L-leucine (with Dr. Fanrong Mu), which is produced on a regular basis. Fully automated syntheses of F-18 FDG and F-18 FLT were subsequently developed and are also regularly used with excellent results. Refinement of various modules designed by Dr. Mangner continues.