Victoire Hanemaayer

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.

Radiometals from liquid targets: 94mTc production using a standard water target on a 13 MeV cyclotron

Solutions containing a high concentration (0.325-0.995 g/ml) of natural-abundance ammonium heptamolybdate tetrahydrate ((NH(4))(6)Mo(7)O(24))·4H(2)O were irradiated at 13 MeV on a proton-beam cyclotron using a standard liquid target. (94m)Tc was produced via the (94)Mo(p,n)(94m)Tc reaction with measured yields of 110±20 MBq for the highest concentrated solution using 5 μA proton beams for 60 min. Saturation yields of up to 40±6 MBq/μA were achieved. Pertechnetate was isolated from the target mixture with 70.9±0.7% efficiency using a solid-phase extraction resin.

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.

Recycling 100Mo for direct production of 99mTc on medical cyclotrons

A scalable recycling technique for the recovery of 100Mo from previously irradiated and chemically processed targets is described. A combined process for both Cu and Ta supported targets and the respective ‘waste’ solutions has been developed. This process involves selectively dissolving Cu target backings from undissolved portions of 100Mo pellets; precipitating Cu(OH)2 at pH 9; electrochemical removal of Cu traces; precipitating (NH4)2MoO4 at pH 2.5-3; thermally decomposing (NH4)2MoO4; and H2 reduction of MoO3 to Mo metal. Radionuclidic decontamination by a factor of ~100 is observed, while overall 100Mo recovery from initial target plating to recycled Mo metal of 96% is achieved.A scalable recycling technique for the recovery of 100Mo from previously irradiated and chemically processed targets is described. A combined process for both Cu and Ta supported targets and the respective ‘waste’ solutions has been developed. This process involves selectively dissolving Cu target backings from undissolved portions of 100Mo pellets; precipitating Cu(OH)2 at pH 9; electrochemical removal of Cu traces; precipitating (NH4)2MoO4 at pH 2.5-3; thermally decomposing (NH4)2MoO4; and H2 reduction of MoO3 to Mo metal. Radionuclidic decontamination by a factor of ~100 is observed, while overall 100Mo recovery from initial target plating to recycled Mo metal of 96% is achieved.

Radionuclidic purity measurements for cyclotron-produced 99mTc via 100Mo(p,2n) at 18 MeV

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 test results agree well with the gamma ray analysis.