2016 marks 40 years of the use of 18F-fluorodeoxyglucose (FDG) – a compound widely used in medicine for the safe and accurate diagnosis and evaluation of diseases impacting millions of patients. TRIUMF emeritus senior scientist and internationally recognized leader in nuclear medicine Dr. Tom Ruth has extensive experience working with 18F. Many individuals at TRIUMF have worked with Dr. Ruth and, using 18F, have made significant contributions to the field of nuclear medicine. Here’s what Dr. Ruth has to say about this revolutionary isotope and how it is used at TRIUMF:
What is 18F and why is it important?
18F is a positron emitting radionuclide with a half-life of 109.7 minutes. It decays 97% via the emission of a positron with the maximum energy of 693 keV. Positron emitting isotopes are the foundation of positron emission tomography (PET). Initially PET made use of the isotopes of the elements of life: 11C, 13N and 15O. Although 18F is not considered to be one of these elements, its physical size is similar to that of the hydroxyl group in compounds, so it can be substituted with minimal alterations to the overall structure of a compound. 18F was the choice to replace the hydrogen in deoxyglucose thus forming 18F-fluorodeoxyglucose (FDG). While FDG is the most widely used PET tracer, there are many tracers that have been developed that use 18F as the label. The chemistry for inserting the 18F is well understood and continues to be developed further.
What is TRIUMF’s connection to 18F?
Presently, there are two primary uses of 18F at TRIUMF. The biggest role has been in the production of 18F-fluorodopa (FD) for studying Parkinson’s disease (PD). Many thousands of scans have been performed using this tracer, which enables neurologists to visualize the change in dopa metabolism in patients suffering from PD. A number of groundbreaking studies have emanated from this work, not the least of which was to see preclinical changes in the dopamine system before progression to disease.
FD is also being used by the BC Cancer Agency (BCCA) to image neuroendocrine tumors. They get it from TRIUMF under a Health Canada special access protocol.
The second biggest use of 18F has been in the production of FDG. We helped the University of Alberta establish their PET program by supplying them with 18F for a couple of years before the installation of their cyclotron. In a similar way, we helped the BCCA begin their program by producing the 18F and synthesizing the FDG on site before they received their cyclotron. We still serve as a back-up source of 18F when the BCCA cyclotron is down for maintenance.
In addition, a number of research projects are continuously underway making use of 18F in the development of new tracers to understand human biology. Many people at TRIUMF have been involved in the work done with 18F, such as Ken Buckley, who played a key role in helping with the targets at TRIUMF.
One interesting side note is that Salma Jivan developed a method for labeling pulp fibers with 18F. The labeled fibers were used in two studies by UBC Chemical Engineering faculty (Mark Martinez) to determine the Crowding Number in paper making, which impacts quality and efficiency. The other study modeled dynamic flow with sudden expansion, which has relevance in many industrial settings that involve fluid flow in pipes.
What role have you played in regards to 18F?
My interest in 18F spans nearly four decades. It started while at Brookhaven National Laboratory where I worked in the Al Wolf group. Al is considered one of the founders of the radiopharmaceutical chemistry field. One of my tasks was to work with Joanna Fowler (who was honored recently for her role in the development of FDG at the Society of Nuclear Medicine and Medical Imaging) on establishing a reliable method for producing 18F- F2 via the bombardment of natural neon (20Ne(d,a)). We carefully went through the various metrics that impacted the yield and quality of the 18F. Once the production became routine, I became Al’s emissary in helping other groups establish a similar capability, visiting the National Institutes of Health in Washington, DC and UCLA in Los Angeles, CA.
In parallel, I explored the production of 18F via the proton bombardment of enriched 18O2 gas. I performed the measurement of the excitation function for this reaction and calculated the thick target yield. The yield from the 18O was several times higher than from neon. Also, newer cyclotrons were being built that accelerated protons only; this started in the early 1980s.
I was recruited to TRIUMF to assist in the development of the UBC/TRIUMF PET program in 1980. At that time we only had access to the 500 MeV beam line where Brian Pate (the Director of the PET program) had installed a gas target. We demonstrated that we could produce 18F via the proton spallation of neon. This route served the program to begin its first studies in PET with FDG studying dementia.
With Mike Adam, Salma Jivan, and John Grierson we developed 18F-fluorodopa (FD). FD became our most widely used tracer for studying Parkinson’s disease.
In parallel, I collaborated with researchers at the University of Wisconsin (Nickles and Daube), where we developed a target system that involves irradiating 18O2 followed by recovery of the oxygen and filling the target with F2-Ne mixture and re-irradiating the target to recover the produced 18F as 18F-F2 by the in situ exchange reaction. This approach is called the 2-shoot method.
Over the years I worked with researchers from UCLA and the company CTI on the development of a low energy reaction using enriched 18O-H2O.
More recently I worked with James Inkster, a graduate student from Simon Fraser University, who developed new labeling methods to be used in aqueous media and other approaches amenable to labeling large biologically active molecules. In this regard I worked with David Perrin who, along with his graduate students, developed an approach that enhances the specific activity of the 18F labeled molecule.
The milestone four decades of FDG’s impacts in nuclear medicine was recently celebrated at the Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging held in San Diego in June 2016. The SNNMI developed this short video which acknowledging some of FDG’s pioneers, including Dr. Tom Ruth.