Thomas J Ruth

TRIUMF · Nuclear Medicine Division

Following a major shortage of ⁹⁹ Mo in the 2009–2010 period, concern grew that the aging reactor production facilities needed to be replaced. Most producers were using highly enriched ²³⁵ U (HEU) as the target material. The Organisation for Economic Co-operation and Development and the International Atomic Energy Agency sought to remedy these issue...

Gas target systems are the main tool for producing [11C]CH4 or [11C]CO2 for nuclear medicine. Modelling has suggested that adsorption to the target body walls plays an important role in the recoverable radioactive yield from a target system. Here, we build on a previous model describing adsorption by including the kinetics of intermediary chemical...

Gas target systems have been used for decades on cyclotrons to produce radionuclides for medical imaging. However, the activity recovered from such targets is often lower than its theoretically predicted value. Past research has suggested that nuclide interactions with the walls of the target body may play a key role in the loss of recoverable radi...

A forced-convection gas target for the production of [11C]CH4 on a 13 MeV cyclotron was constructed and tested. A small fan was incorporated into the back of the target, which mixes the target gas during irradiation. The effect of the forced convection alone on the target operation and the [11C]CH4 yield was measured. Forced convection improved the...

The development of alpha-emitting radiopharmaceuticals using ²¹¹At requires quantitative determination of the time-dependent nature of the ²¹¹At biodistribution. However, imaging-based methods for acquiring this information with ²¹¹At have not found wide-spread use because of its low abundance of decay emissions suitable for external detection. In...

Background: Markers of neuroinflammation are increased in some patients with LRRK2 Parkinson's disease compared with individuals with idiopathic Parkinson's disease, suggesting possible differences in disease pathogenesis. Previous PET studies have suggested amplified dopamine turnover and preserved serotonergic innervation in LRRK2 mutation carri...

TRIUMF has a long history of medical isotope production. For more than 40 years, the Life Sciences Division at TRIUMF has produced isotopes for Positron Emission Tomography (PET) for the local hospitals. Recently, the division has taken on the challenge to expand the facility's isotope repertoire to isotopes for imaging to treatment. At the smalles...

This publication presents a comprehensive overview of the technologies involved in the production of cyclotron based 99mTc. These would include techniques relevant to preparation of targets, irradiation of targets under high beam currents, target processing, target recovery and quality control of the final product. The publication provides broad in...

The purpose of this work is to introduce a universal mathematical model to explain a gas target behaviour at steady-state time scale. To obtain our final goal, an analytical model is proposed to study the pressure rise in the targets used to produce medical isotopes on low-energy cyclotrons. The model is developed based on the assumption that durin...

Introduction: The availability of (211)At for targeted alpha therapy research can be increased by the (211)Rn/(211)At generator system, whereby (211)At is produced by (211)Rn electron capture decay. This study demonstrated the feasibility of using generator-produced (211)At to label monoclonal antibody (BC8, anti-human CD45) for preclinical use, f...

Mass-separated francium beams (²¹¹Fr or ²¹³Fr) were implanted into solid targets for producing ²¹¹Rn (14.6 h half-life) or ²⁰⁹At (5.41 h), in situ. ²¹¹Rn was transferred to dodecane and isolated from contaminants, providing sources for ²¹¹At (7.21 h) production by ²¹¹Rn decay (73%). ²⁰⁹At was recovered with high radionuclidic purity in aqueous solu...

Cyclotron-produced 99mTc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99mTc. However, the small amount of ⁹²⁻⁹⁸Mo in the irradiation of enriched ¹⁰⁰Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities...

The radionuclidic purity of cyclotron-produced 99mTc has been measured by gamma ray spectroscopy and compared to the results of a quick release test modeled after the molybdenum breakthrough test performed on generator-derived 99mTc. Excellent radionuclidic purity is reported for samples produced at BCCA during our clinical trial. The quick release...

Purpose:The short-range, densely ionizing α-particles emitted by ²¹¹At (t1/2=7.2h) are well suited for the treatment of diffuse microscopic disease, using cancer targeting biomolecules. ²¹¹At availability is limited by the rarity of α-cyclotrons required for standard production. Image-based dosimetry is also limited for ²¹¹At, which emits low inten...

Overexpresssion of HER-2 in the MDA-MB-435/LCC6 (LCC6(HER-2)) tumour model is associated with significantly increased hypoxia and reduced necrosis compared to isogenic control tumours (LCC6(Vector)); this difference was not related to tumour size or changes in vascular architecture. To further evaluate factors responsible for HER-2-associated chang...

From the efforts of a number of Canadian institutions and private industry collaborations, direct production of 99mTc using medical cyclotrons has recently been advanced from a 1970's academic exercise to a commercial, economically viable solution for regional production. Using GE PETtrace 880 machines our team has established preliminary saturated...

In response to the recognized fragility of reactor-produced 99Mo supply, direct production of 99mTc via 100Mo(p,2n)99mTc reaction using medical cyclotrons has been investigated. However, due to the existence of other Molybdenum (Mo) isotopes in the target, in parallel with 99mTc, other technetium (Tc) radioactive isotopes (impurities) will be produ...

Cyclotron production of 99mTc through the 100Mo(p,2n)99mTc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. Like most radioisotope production methods, cyclotron production of 99mTc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is imp...

Introduction: Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview...

Cyclotron production of (99m)Tc through the (100)Mo(p,2n) (99m)Tc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace...

(99m)Tc is the most widely used radionuclide in nuclear medicine. The reactor stoppages that occurred in recent years illustrated the vulnerability of the availability of radiotracers for imaging. With many of the reactors due for shutdown over the next 5-10 y, alternative routes to producing the (99)Mo/(99m)Tc pair are being explored. This brief r...

Unlabelled: We report a kit-based approach for the purification of sodium pertechnetate ((99m)TcO4 (-)) from solutions with high MoO4 (2-) content. Methods: Cross-linked polyethylene glycol resins (ChemMatrix) were used to separate (99m)Tc and molybdenum in 4N NaOH. The resins were loaded at various flow rates and eluted with water to release (9...

Cyclotron production of 99m Tc and 186 Re stands as an invaluable method to produce both radiometals. This method of preparation has become attractive to (1) combat the impending shortage of 99m Tc due to aging reactors and (2) produce 186 Re with higher specific activities. Our proof of concept studies indicate that the use of the refractory carbi...

The cyclotron-based 100Mo(p,2n)99mTc reaction has been proposed as an alternative method for solving the shortage of 99mTc. With this production method, however, even if highly enriched molybdenum is used, various radioactive and stable isotopes will be produced simultaneously with 99mTc. In order to optimize reaction parameters and estimate potent...

(99m)Tc is currently produced by an aging fleet of nuclear reactors, which require enriched uranium and generate nuclear waste. We report the development of a comprehensive solution to produce (99m)Tc in sufficient quantities to supply a large urban area using a single medical cyclotron. A new target system was designed for (99m)Tc production. Targ...

Recent synthetic applications conducted on microfluidic chips have shown improved yields and shorter reaction times as compared to conventional methods. These have generated great interest in the microfluidic synthesis of radiotracer compounds with short lived radioisotopes, such as carbon-11 (t1/2 – 20.4 min). For the purpose of microreactor desig...

Objectives: Several groups have reported success in the production of technetium-99m (Tc-99m) through proton irradiation of molybdenum-100 (Mo-100) via the 100Mo(p,2n)99mTc reaction. Most published methods have used natural or enriched Mo foils or melted/sintered pellets for target manufacture. The purpose of this study was to experiment with a var...

C-labelled radiotracers such as [¹¹C]raclopride are produced in a process that can take between 45 and 60 min to complete. These conventional approaches can consume upwards of 75% of the ¹¹C (t1/2 = 20 min) due to radioactive decay alone, even more if synthesis losses are considered. To compensate, a large starting quantity of radioactive precursor...

Purpose: Manganese(II) is employed as a contrast agent with magnetic resonance imaging (MRI) for study of neuronal activation in rats and mice. However, at the concentrations required for MRI, Mn may induce pharmacological or toxic effects. Positron emission tomography (PET) imaging of (52)MnCl2 at tracer doses has the potential to allow similar M...

There is a growing need for the production of radioisotopes for both diagnostic and therapeutic medical applications. Radioisotopes that are produced using the (n,γ) or (γ,n) reactions, however, typically result in samples with low specific activity (radioactivity∕gram) due to the high abundance of target material of the same element. One method to...

Raising the (18) F(3) -BAr: Specific activities of most (18) F-labeled radiotracers fall below 2 Ci μmol(-1) , yet (18) F-aryltrifluoroborate synthesis affords specific activities as high as 15 Ci μmol(-1) . This has been confirmed by using click chemistry to link an [(18) F]-ArBF(3) (-) to rhodamine and thereby demonstrating a rapid and generaliza...

Rund zehn Mal höhere spezifische Aktivität: Die meisten 18F‐markierten Radiotracer haben eine spezifische Aktivität unter 2 Ci μmol−1, während mit 18F‐Aryltrifluoroboraten Werte bis 15 Ci μmol−1 möglich sind. Dies wurde durch das Anknüpfen eines [18F]‐ArBF3−‐Anions an Rhodamin mithilfe der Klickchemie bestätigt, was eine rasche und verallgemeinerba...

Introduction Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in...

Technetium-99m (99mTc) production using medical cyclotrons has been proposed to solve the anticipated shortage of 99mTc, which traditionally is obtained from the reactor-produced generators. Optimizing reaction conditions to maximize 99mTc production yield becomes crucial. Additionally, since besides 99mTc, many other undesirable stable and radioac...

A method to produce solid 100 Mo metal targets capable of withstanding proton irradiation with a power density of up to 1.1 kW/cm2 has been developed. The method of choice involves the electrodeposition of enriched 100 Mo powder onto a tantalum backing, followed by high-temperature sintering in order to afford a coating that is sufficient t...

Recent disruptions in the molybdenum-technetium generator supply chain prompted a review of non-reactor based production methods for both 99Mo and 99mTc. Small medical cyclotrons (E p ~ 16–24 MeV) are capable of producing Curie quantities of 99mTc from isotopically enriched 100Mo using the 100Mo(p,2n)99mTc reaction. Unlike most other metallic targe...

In an effort to understand the possibility of using PET as a tool for dose verification after proton therapy in ocular melanomas, a Lucite phantom was irradiated at the proton therapy facility at TRIUMF with a raw and spread-out Bragg peak of 74 MeV protons and scanned in two different PET scanners at UBC. A tantalum clip, used as a marker during p...

94 m Tc was produced in a liquid target loaded with a molybdenum-salt solution. This novel technique allows for the irradiation of metals dissolved in a liquid solution, normally only available in metal powder or foil form. By using this approach, the existing liquid targets and transfer infrastructure of many PET cyclotrons can be used to prod...

Nucleophilic incorporation of [(18)F]F(-) under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to (18)F-labelled biomarkers for PET che...

While many radioactive isotopes in use today are found in nature, many more are artificially produced by irradiating target materials with nuclear particles. Two different technologies can provide the energetic particles needed: nuclear reactors, which produce a flux of neutrons, and particle accelerators, which produce a flux of charged particles....

Biologically-targeted alpha-particle radiation is the basis of new and promising treatments for eliminating disseminated micrometastases and the residual microscopic malignancies that remain after surgery or radiation therapy. The short-range alpha-particles are highly cytotoxic and capable of inactivating single, isolated cancer cells which may ot...

We studied the interactive effects of iron (Fe) and copper (Cu) availability on the growth rates, Cu quotas, and steady‐state Cu‐uptake rates (ρssCu) of 12 phytoplankton (from four classes and two marine environments). A mixed‐effect statistical model indicated that low Fe significantly decreased phytoplankton growth rates. In contrast, lowering Cu...

This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers l...

The shortage of reactor-produced molybdenum-99 ((99)Mo, t(½)=66 h) has renewed interest in alternative production methods of its daughter isotope, technetium-99m ((99m)Tc, t(½)=6.02 h). While adsorption chromatography serves as a mechanism for selective elution of sodium pertechnetate from technetium generators, this method of purification is not s...

Parkinson's disease is a relentlessly progressive neurodegenerative disease. Breakdown of compensatory mechanisms influencing putaminal dopamine processing could contribute to the progressive motor symptoms. We studied a cohort of 78 subjects (at baseline) with sporadic Parkinson's disease and 35 healthy controls with multi-tracer positron emission...

Marimastat, a clinically trialed drug developed to treat breast cancer by inhibiting cancer-associated matrix metalloproteases (MMPs), was linked to an aryl boronic ester for single-step [F-18]-aqueous fluoride capture and the labeled product revealed tumor associated MMP activity in vivo. Herein, we report important radiosynthetic attributes for l...

Over 80% of all Nuclear Medicine procedures make use of the radionuclide Tc-99 for SPECT imaging of heart disease, cancer and other disorders. Historically TC-99 has been produced from a generator through the decay of Mo-99 where the Mo-99 is a fission product of U-235. Five reactors around the world supply the market. However, these reactors are a...

Recent acute shortage of medical radioisotopes prompted investigations into alternative methods of production and the use of a cyclotron and ¹⁰⁰Mo(p,2n)(99m)Tc reaction has been considered. In this context, the production yields of (99m)Tc and various other radioactive and stable isotopes which will be created in the process have to be investigated...

The cyclotron-based (100)Mo(p,2n)(99m)Tc transformation has been proposed as a viable alternative to the reactor based (235)U(n,f)(99)Mo→(99m)Tc strategy for production of (99m)Tc. Despite efforts to theoretically model the amount of ground-state (99g)Tc present at end of bombardment for the (p,2n) reaction, experimental validation has yet to be pe...

Purpose: To investigate radiationdosimetry for 99mTc produced by medical cyclotrons, based on theoreticalreaction cross?sections and yields. Several other technetiumisotopes produced in a cyclotron are chemically inseparable from 99mTc. This could increase patient absorbed dose. We compared the resulting doses to those from 99mTc produced by conven...

To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [¹¹C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular...

PET is a functional imaging technique based on detection of annihilation photons following beta decay producing positrons. In this paper, we present the concept of a new PET system for preclinical applications consisting of a ring of twelve time projection chambers filled with liquid xenon viewed by avalanche photodiodes. Simultaneous measurement o...

A proof-of-principle approach for the production of intense (~108/s) radioactive ion beams, which differs from the standard ISOL (Isotope Separation On-Line) technique, has been demonstrated successfully using 11C at the TRIUMF laboratory. This approach uses 13 MeV protons produced by a medical cyclotron and should be useful for a range of radioiso...

The reaction of elemental fluorine with phenyl derivatives of tin, lead, germanium, silicon, mercury, and thallium has been studied with the aim of developing a general method for labelling aromatic compounds with radioactive 18F. Rapid synthesis of fluorobenzene was achieved in varying chemical yields up to 70%, depending largely upon the metal su...