Cyclotron Facility

The cyclotron facility was built in 1985 and is a below grade building containing about 5100 sq. ft. of space with a Japan Steel Works BC3015, 30 MeV cyclotron. The machine is capable of accelerating p, d, 3He, and 4He. Beam currents of 10-20 µA are typical with a maximum current capability of 30-40 µA. Currently we produce 11C, 13N, 15O, and 18F (both as a gas and a liquid) for radiopharmaceutical production. We use protons at 22 MeV to produce 11C, 13N and most 18F-labeled tracers, and deuterons at 11 MeV for 15O, 18F-DOPA and 18F-EF-5, (the latter two are produced from 18F gas).

cyclotron

The facility is divided into two sections; a clinical production laboratory where 18F-FDG, 18F-DOPA, 18F-EF-5 and 13N compounds are produced, and a multi-use research area in which new radiopharmaceuticals for cell studies, ligand labeling, and animal studies are developed. The clinical lab currently has one general-purpose hot cell and two mini hot cells dedicated to 18F-FDG production. The lab has a fume hood for prep work and a laminar flow hood for aseptic assembly, QC, and product testing.

Equipment within the production lab includes an integrated high-pressure liquid chromatography (HPLC) and gas chromatography (GC) system from Agilent and a thin-film liquid chromatography (TLC) scanner that is also tied to the Agilent software. Two GE MX Coincidence boxes are used for FDG production. All human use products are subjected to QC testing within this production facility. The production facility has a depyrogenation oven, an autoclave, secure storage areas for storage of materials to be used with human use compounds, an incubation refrigerator, a laboratory refrigerator/freezer for storage, 2 Capintec dose calibrators, and a Germanium based radiation detector for radionuclidic identification of products that is instrumented with a computer based multi-channel analyzer.

The multi-use research area includes four dedicated hot cells where 18F can be remotely delivered. Two of the hot cells are for 11C work; one contains a GE MeI synthesis unit, also directly plumbed to the target and an Agilent HPLC system capable of working with a prep column for separation of product. It also has a Methyl-Triflate column. Final QC of these products is normally performed in the production lab before release of the product but can also be done using the qualified backup QC system. The research area also includes two fume hoods and bench space for preparation of compounds and work. Cold chemistry HPLC systems are available as is a multi-sample well counter. All critical equipment (ovens, autoclaves, HPLC QC stations, etc.) are under service contracts, validated and backed up by duplicate systems. Outside of the clean-room areas is another multi-sample well counter for tissue samples that are not allowed within the pharmaceutical production clean areas.

The cyclotron facility includes the capability to produce SPECT research compounds. We have a dedicated bio-safety hood for SPECT compounds, and an additional, validated HPLC/QC station for these compounds, addition refrigeration, ovens, and other equipment. We have produced 99mTc labeled Trodat and 123I labeled ADAM and IMPY. For these last two compounds a fume hood is directly adjacent to the bio-safety hood for the iodine work. SPECT and PET Compounds have separate equipment and waste streams.

cyclotron

In the 2010, we have added an IBA 18 MeV Cyclone machine and installed it in an expanded vault next to the existing JSW cyclotron. This addition greatly enhances our ability to produce an increased number of radiotracers for our research studies in PET. The new cyclotron provides for higher beam currents than are available on the JSW machine. Relative to the JSW machine, the 18F- production yield increases from 1.5 Ci to 10 Ci and 11C yield increases from 1 Ci to 2.5 Ci, thereby increasing yields of research tracers. Deuteron production of 18F2 is approximately the same due the higher energy of the deuteron beam (11 MeV) from the JSW machine.

While the JSW can only irradiate one target at a time, the IBA is capable of irradiating two targets simultaneously. Despite its older design and lower yields, the JSW as an advantage of a higher particle energy and capability to produce alpha particles; this is a rare and valuable asset. In particular, the alphas allow production of 211At which has potential in targeted systemic therapy. The expanded facility will be designed for GMP manufacturing and will allow us to add up to five additional hot cells/distribution cells for 18F and 11C work to increase our capacity for radiotracer production. The added chemistry space is about 1000 sq. ft.