One of the cyclotrons is a Japan Steel Works (JSW) BC3015 30 MeV machine, capable of accelerating protons, deuterons, 3He, and 4He. Beam currents of 10-20 mA are typical with a maximum current capability of 60 mA. In 2009, an IBA 18/9 MeV Cyclone cyclotron was added into an expanded vault adjacent to the existing JSW cyclotron. The second cyclotron provides for higher beam currents than are available on the JSW cyclotron. As a result, the [18F]F- production yield increases from 2 Ci to 12 Ci and; [11C]CO2 yield increases from 3 Ci to 4 Ci, thereby increasing yields of research radiotracers. While the JSW can only irradiate one target at a time, the IBA is capable of irradiating two targets simultaneously and has been the main workhorse cyclotron. In addition to [18F]F- production, this cyclotron is also used for [18F]F2 bombardment for electrophilic radiosyntheses. Despite its older design and lower yields, the JSW has an advantage of a higher particle energy and capability to produce alpha particles; this is a rare and valuable asset and enables our facility to produce novel radionuclides for biomedical research. In particular, the JSW currently is used to produce At-211, a radionuclide that has potential in targeted systemic radiotherapy.
The facility is divided into two sections: a clinical production laboratory where the radiopharmaceuticals used in routine diagnostic scans and clinical studies are produced, and a multiuse research area in which new radiotracers are developed for cell studies, animal studies and other research uses. The following table lists the radiopharmaceuticals that are produced on routine basis.
Name of the radiopharmaceutical
|
Status |
Application |
[18F] Fludeoxyglucose Injection ([18F] FDG)
|
ANDA
|
Routine diagnostic scans
|
[11C] Acetate
|
IND
|
Cardiac, cancer metabolism
|
[18F] Fluorothymidine ([18F]FLT)
|
IND
|
Cancer; cell proliferation
|
[3H] Cholesterol
|
IND
|
|
[18F] ISO-1
|
IND
|
Cancer; cell proliferation
|
[18F] Fluortriopride ([18F] FTP)
|
IND
|
D3 specific brain agent
|
[18F] Fluoroestradiol ([18F] FES)
|
IND
|
Cancer; estrogen status
|
[18F] FluorThanatrace ([18F] FTT)
|
IND
|
Cancer; PARP activation
|
[18F] EF5
|
IND
|
Cancer; Hypoxia agent
|
[18F] Fluorodopa
|
IND
|
Hyperinsulinism, brain dopamine level
|
[18F] 5-fluorodeoxycyctidine
|
IND
|
Cancer; cell differentiation
|
[11C] Glutamine
|
Pre-clinical
|
Cancer metabolism
|
[18F] 2S,4R)4-Fluoroglutamine ([18F] 4F-Gln)
|
Pre-clinical
|
Cancer metabolism
|
[18F] DHE
|
Pre-clinical
|
ROS status
|
The clinical production laboratory is operated under cGMP regulations. The facility currently has two laminar flow dispensing hot cell, ten mini hot cells and one research hot cell. Three of the mini hot cells house two GE MX Coincidence boxes and one Naptis Perform module that are dedicated to daily [18F]FDG production. In addition, there are two Synthera synthesis modules and one All-in-One module for nucleophilic fluorination. A custom-built electrophilic fluorination module is dedicated for clinical studies. On the C-11 label radiopharmaceuticals side, two Synthra MeI Research modules are available in the mini hot cells for C-11 methylation reactions using [11C]MeI or [11C]methyl triflate and one custom-built module for the synthesis of [11C] Acetate and [11C] Palmitate.
Equipment within the cGMP quality control (QC) lab includes three integrated high-pressure liquid chromatography (HPLC), one ultra performance liquid chromatography (UPLC), three gas chromatography (GC) systems and three thin-film liquid chromatography (TLC) scanners. The analytical systems are operated with Part 11 compliant software. Three calibrated portable endotoxin test systems are used for endotoxin tests and three certified laminar flow hood are used for aseptic manipulations. Custom-built bubble point testing stations are available for filter membrane integrity test. All QC use equipment, including analytical equipment and other equipment, such as incubators, refrigerators, balances and dose calibrators are also under regular calibration/maintenance schedule. The environment where cGMP activity took place is under regular monitoring schedule.
The multiuse research area has two hot cells where [18F]F- can be remotely delivered for low-dose ligand development and high-dose scale up syntheses. Four hot cells are for C-11 work: two contain a GE MeI synthesis unit in each of the hot cell, one contains an in-house [11C]CN synthesis unit, and one contains a modified Aseptic Lab synthesis module for radiolabeling with [11C]CO2. Additionally, there is a dedicated hot cell for At-211 related research development. HPLC systems capable of working with a semi-prep column for product purification is available in most of the hot cells.
Cyclotron Facility Staff
Robert H. Mach, PhD., Professor, Director of Cyclotron Facility
Alexander Schmitz, PhD., Co-Director of Production
Hsiaoju (Sharon) Lee, PhD., Co-Director of Production
Mehran Mekvandi, Pharm D. R. Ph. Radiopharmacist
Rahul Poria, MS. R. Ph. Radiopharmacist
Alexander Kachur, PhD., production/tracer development
Anthony Page, quality control
Adam Runkle, cyclotron operation/production
Desiree Perry, document control
David Schaub, cyclotron operation
Iljung Lee, PhD., research
Lawrence Toto, cyclotron operation
Jacek Dobrowolski, cyclotron operation/production
Prashanth Padakanti, PhD., production/tracer development
Shihong Li, production/quality control