Stefan K. Zeisler

Implementation of Multi-Curie Production of 99mTc by Conventional Medical Cyclotrons

99mTc 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 99mTc in sufficient quantities to supply a large urban area using a single medical cyclotron. Methods: A new target system was designed for 99mTc production. Target plates made of tantalum were coated with a layer of 100Mo by electrophoretic deposition followed by high-temperature sintering. The targets were irradiated with 18-MeV protons for up to 6 h, using a medical cyclotron. The targets were automatically retrieved and dissolved in 30% H2O2. 99mTc was purified by solid-phase extraction or biphasic exchange chromatography. Results: Between 1.04 and 1.5 g of 100Mo were deposited on the tantalum plates. After high-temperature sintering, the 100Mo formed a hard, adherent layer that bonded well with the backing surface. The targets were irradiated for 1–6.9 h at 20–240 μA of proton beam current, producing up to 348 GBq (9.4 Ci) of 99mTc. The resulting pertechnetate passed all standard quality control procedures and could be used to reconstitute typical anionic, cationic, and neutral technetium radiopharmaceutical kits. Conclusion: The direct production of 99mTc via proton bombardment of 100Mo can be practically achieved in high yields using conventional medical cyclotrons. With some modifications of existing cyclotron infrastructure, this approach can be used to implement a decentralized medical isotope production model. This method eliminates the need for enriched uranium and the radioactive waste associated with the processing of uranium targets.

44gSc production using a water target on a 13 MeV cyclotron

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 development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t1/2=3.97 h, Eavg,β⁺=1.47MeV, branching ratio=94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. METHODS Solutions containing a high concentration (1.44-1.55g/mL) of natural-abundance calcium nitrate tetrahydrate (Ca(NO₃)2·4 H₂O) were irradiated on a 13MeV proton-beam cyclotron using a standard liquid target. (44g)Sc was produced via the ⁴⁴Ca(p,n)(44g)Sc reaction. RESULTS (44g)Sc was produced for the first time in a solution target with yields sufficient for early radiochemical studies. Saturation yields of up to 4.6 ± 0.3 MBq/μA were achieved using 7.6 ± 0.3 μA proton beams for 60.0 ± 0.2 minutes (number of runs n=3). Experimental data and calculation results are in fair agreement. Scandium was isolated from the target mixture via solid-phase extraction with 88 ± 6% (n=5) efficiency and successfully used for radiolabelling experiments. The demonstration of the production of ⁴⁴Sc in a liquid target greatly improves its availability for tracer development.

Production of 64Cu on the Sherbrooke TR-PET cyclotron

At energies £15 MeV, 64Cu is most readily produced using the 64Ni(p,n)64Cu reaction. Space restrictions in the TR-PET target selector required a target system of compact design that would still allow the quick and easy removal of the irradiated target. The target consists of a 64Ni-plated rhodium disc held in place by a threaded cooling assembly. For removal, the cooling block is rotated slightly, allowing the disc to fall into a shielding container. The nickel is dissolved and the 64Cu separated by anion exchange or electrochemical deposition. Yields of up to 330 mCi of radiochemically pure 64Cu have been obtained.

Cross-Linked Polyethylene Glycol Beads to Separate 99mTc-Pertechnetate from Low-Specific-Activity Molybdenum

We report a kit-based approach for the purification of sodium pertechnetate (99mTcO4−) from solutions with high MoO42− content. Methods: Cross-linked polyethylene glycol resins (ChemMatrix) were used to separate 99mTc and molybdenum in 4N NaOH. The resins were loaded at various flow rates and eluted with water to release 99mTc. The 99mTc solution was passed through a cation exchange resin and an alumina cartridge, followed by saline elution. This process was tested with cyclotron-produced 99mTc using an automated system and disposable kits. Results: Optimal results were obtained by loading 500 mg of resin at flow rates of up to 3.1 mL/min, with quantitative extraction of 99mTc from the molybdate solution and complete release of 99mTc after elution with water. The automated system was highly efficient at isolating Na99mTcO4 within minutes, with a recovery rate of 92.7% ± 1.1% (mean ± SD) using cyclotron-produced 99mTc. Conclusion: ChemMatrix resins were highly effective at separating 99mTcO4− from molybdate solutions.

Production of Y-86 and other radiometals for research purposes using a solution target system.

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 of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. METHODS Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. RESULTS We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/μA and yield = 3.17 MBq/μA), (86)Y (Asat = 31 MBq/μA and yield = 1.44 MBq/μA), and (68)Ga (Asat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate (89)Zr.

A proof of principle for targetry to produce ultra high quantities of 18F-fluoride

The production of 18F-fluoride from a gas target which utilizes the (18)O(p,n)18F reaction is described. Proof-of-principle experiments demonstrate that it is possible to design and build such a target that can be used routinely to produce terabecquerel (curie) quantities of 18F when operated at 100 microA.

Thermal modeling of high-current solid targets

Production demands at TRIUMF have pushed present target designs to the limit of their beam current capacity. A thermal analysis of the present high-current solid production targets has been carried out in order to increase radioisotope production rates through maximizing current handling capability. This paper describes the optimization of a 5° incident angle solid target for radioisotope production in service on the TRIUMF TR-30 cyclotron. Target materials compared include silver and Glidcop®,1 a dispersion-strengthened copper composite. A summary of comparative results is presented.

A new transfer system for solid targets

As part of a collaborative research project funded by Natural Resources Canada, TRIUMF has designed and manufactured solid target and solid target processing systems for the production of technetium-99m using small medical cyclotrons. The system described herein is capable of transporting the target from a hotcell, where the target is loaded and processed, to the cyclotron and back again. The versatility of the transfer system was demonstrated through the successful installation and operation on the ACSI TR 19 at the BC Cancer Agency, the GE PETtrace cyclotrons at Lawson Health Research (LHRI) and the Centre for Probe Development and Commercialization (CDPC).

Preparation of [48V]-VO2+ for biomedical studies

A new method for the highly efficient separation of48V for radiotracer experiments is presented. It is based on the proton irradiation of a high purity Ti plate which is dissolved in sulfuric acid to form Ti3+ and V4+. Both ions are quantitatively absorbed on AG50W-X8 cation exchange resin and are converted to the respective higher valence state by an on-column reaction with diluted nitric acid and hydrogen peroxide. The eluate containing V5+ is evaporated to dryness in presence of sulfuric acid and treated with ethanol to reduce [48V]-vanadate to [48V]-vanadyl for labeling experiments in pharmaceutical research.

Boron stripper foils for particle accelerators

Micromatter Technologies Inc., now located in Surrey B.C., Canada, is a worldwide supplier of pure and boron containing diamond-like carbon (DLC) stripper foils ranging from 10 nm to 10 μm. These foils are manufactured in-house using pulsed laser deposition. Continuing our research into novel production methods and alternative materials to be used as beam strippers for heavy elements and in particular for tandem particle accelerators, pure boron foils were prepared by laser plasma ablation of a disc shaped boron sputter target. Foil thickness between 10 nm to approximately 0.7 μm were achieved. The new boron foils showed considerably less stress, higher mechanical strength and better flexibility than comparable DLC films.