Katherine Gagnon

Cyclotron production of 99mTc: Experimental measurement of the 100Mo(p,x)99Mo, 99mTc and 99gTc excitation functions from 8 to 18 MeV

INTRODUCTION 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 performed. The co-production of (99g)Tc may have important implications in both the subsequent radiopharmaceutical chemistry and patient dosimetry upon injection. METHODS To determine the extent of (99g)Tc co-production, we have experimentally measured the (100)Mo(p,x)(99)Mo, (99m)Tc, and (99g)Tc excitation functions in the 8-18 MeV range using a combination of natural abundance and 97.42% enriched (100)Mo foils along with γ-ray spectrometry and ICP-MS. Although the excitation functions for production of (99)Mo and (99m)Tc have been presented previously in the literature, to the best of our knowledge, this work presents the first experimental evaluation of the (100)Mo(p,2n)(99g)Tc excitation function. RESULTS From the experimental cross-section measurements, the (99m)Tc production yields and (99m)Tc/(99m+g)Tc nuclei ratio were calculated for various thick target irradiation conditions. Results suggest that TBq quantities of (99m)Tc can be achieved with a (99m)Tc/(99m+g)Tc nuclei ratio that is on par with the current (99)Mo/(99m)Tc generator standard eluted at a 24-h frequency. CONCLUSION These findings suggest that the cyclotron production of (99m)Tc may be a feasible alternative to the current reactor-based production strategy.

Iodine-124: A Promising Positron Emitter for Organic PET Chemistry

The use of radiopharmaceuticals for molecular imaging of biochemical and physiological processes in vivo has evolved into an important diagnostic tool in modern nuclear medicine and medical research. Positron emission tomography (PET) is currently the most sophisticated molecular imaging methodology, mainly due to the unrivalled high sensitivity which allows for the studying of biochemistry in vivo on the molecular level. The most frequently used radionuclides for PET have relatively short half-lives (e.g. 11C: 20.4 min; 18F: 109.8 min) which may limit both the synthesis procedures and the time frame of PET studies. Iodine-124 (124I, t1/2 = 4.2 d) is an alternative long-lived PET radionuclide attracting increasing interest for long term clinical and small animal PET studies. The present review gives a survey on the use of 124I as promising PET radionuclide for molecular imaging. The first part describes the production of 124I. The second part covers basic radiochemistry with 124I focused on the synthesis of 124I-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the future prospective of using the long-lived positron emitter 124I in the field of organic PET chemistry and molecular imaging.

An automated module for the separation and purification of cyclotron-produced 99mTcO4-.

INTRODUCTION 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 sufficient for many alternative production methods. Several ion-separation/solid phase extraction chromatography methods are known, yet none have been demonstrated on cyclotron-produced [(99m)Tc]TcO(4)(-). Herein we describe the design, manufacture and optimization of a remotely operated module for the purification of sodium pertechnetate from a bulk solution of molybdate. METHODS The automated purification module was designed to separate [(99m)Tc]TcO(4)(-) using either Dowex 1x8 or an Aqueous Biphasic Extraction Chromatography (ABEC) resin. (100)Mo composite targets were irradiated with 18.5 MeV protons for 10 μA·h using an ASCI TR19 cyclotron. Once purified, the radiopharmaceutical quality of (99m)TcO(4)(-) isolated from each process (Dowex and/or ABEC) was established by assaying for molybdate breakthrough, alumina levels and, in the case of the Dowex approach, residual organics. RESULTS The separation processes are efficient (75% for Dowex, 90% for ABEC) and complete in less than 30 min. Overall, up to 2.1 GBq of (99m)Tc was produced using the (100)Mo(p,2n)(99m)Tc transformation, processed using the separation module and subjected to a detailed chemical and radionuclidic analysis. Due to its expense and limited availability, (100)MoO(4)(2-) was recovered in >90% yield using a precipitation/filtration/lyophilization approach. CONCLUSIONS Na[(99m)Tc]TcO(4) was produced using a medical cyclotron, recovered using an automated purification module and found to exceed all established quality control parameters.

A new and simple calibration-independent method for measuring the beam energy of a cyclotron

This work recommends a new and simple-to-perform method for measuring the beam energy of an accelerator. The proposed method requires the irradiation of two monitor foils interspaced by an energy degrader. The primary advantage of the proposed method, which makes this method unique from previous energy evaluation strategies that employ the use of monitor foils, is that this method is independent of the detector efficiency calibration. This method was evaluated by performing proton activation of (nat)Cu foils using both a cyclotron and a tandem Van de Graaff accelerator. The monitor foil activities were read using a dose calibrator set to an arbitrary calibration setting. Excellent agreement was noted between the nominal and measured proton energies.

Assessing the performance and longevity of Nb, Pt, Ta, Ti, Zr, and ZrO2-sputtered Havar foils for the high-power production of reactive [18F]F− by proton irradiation of [18O]H2O

As water-soluble ionic contaminants, which arise following proton irradiation of [18O]H2O have been associated with decreased [18F]FDG yields, the minimization of these contaminants is an asset in improving the [18F]F reactivity. To this end, we have previously demonstrated that the use of Nb-sputtered Havar foils results in decreased radionuclidic and chemical impurities in proton irradiated [18O]H2O, improved [18F]FDG yields, and improved [18F]FDG yield consistency when compared with non-sputtered Havar. Resulting from the highly reactive chemical microenvironment within the target however, this niobium layer is observed to degrade over time. To find a material that displays increased longevity with regards to maintaining high [18F]F reactivity, this project extensively investigated and compared Havar foils sputtered with Nb, Pt, Ta, Ti, Zr and ZrO₂. Of the materials investigated, the results of this study suggest that Ta-sputtered Havar foil is the preferred choice. For similar integrated currents (~1,000,000 μA min), when comparing the Ta-sputtered Havar with Nb-sputtered Havar we observed: (i) greater than an order of magnitude decrease in radionuclidic impurities, (ii) a 6.4 percent increase (p=0.0025) in the average TracerLab MX [18F]FDG yield, and (iii) an overall improvement in the FDG yield consistency. Excellent performance of the Ta-sputtered foil was maintained throughout its ~1,500,000 μA min lifetime.

Separation of [(99m)Tc]pertechnetate and molybdate using polyethylene glycol coated C18 and C30 resins.

Hydrophobic adsorbents such as C18 and C30 were coated with PEG and subsequently used for the separation of Mo/Tc. The most effective resin for adsorbing PEG was the C18-U resin, which demonstrated a coating capacity of 97.6±2.8mg PEG per g of resin. The ability to adsorb pertechnetate was proportional to the amount of PEG coated on the hydrophobic resin. The [(99m)Tc]pertechnetate recovery during the separation of cyclotron produced (99m)Tc from (100)Mo was 91.8±0.3% (n=2). The resultant product met relevant USP monograph specifications.

Radiotracers Based on Technetium-94m

This review gives a survey on the use and applications of technetium-94m ((94m)Tc) as a non-conventional positron emission tomography (PET) radionuclide for molecular imaging. The first part of this review describes the production and processing of (94m)Tc. The second part covers basic concepts of technetium coordination chemistry with a special focus on the synthesis of (94m)Tc-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the prospects of using (94m)Tc in the field of PET chemistry and molecular imaging.

Spectral calibration of EBT3 and HD-V2 radiochromic film response at high dose using 20 MeV proton beams

Radiochromic film is used extensively in many medical, industrial, and scientific applications. In particular, the film is used in analysis of proton generation and in high intensity laser-plasma experiments where very high dose levels can be obtained. The present study reports calibration of the dose response of Gafchromic EBT3 and HD-V2 radiochromic films up to high exposure densities. A 2D scanning confocal densitometer system is employed to carry out accurate optical density measurements up to optical density 5 on the exposed films at the peak spectral absorption wavelengths. Various wavelengths from 400 to 740 nm are also scanned to extend the practical dose range of such films by measuring the response at wavelengths removed from the peak response wavelengths. Calibration curves for the optical density versus exposure dose are determined and can be used for quantitative evaluation of measured doses based on the measured optical densities. It was found that blue and UV wavelengths allowed the largest dynamic range though at some trade-off with overall accuracy.

Robust high-yield ~1 TBq production of cyclotron based sodium [ 99m Tc]pertechnetate

This paper presents the irradiation and processing of high-current 100Mo targets at the University of Alberta (UofA) in a GMP compliant setting. For purpose of comparison with a second production facility, additional studies at Centre Hospitalier Universitaire de Sherbrooke (CHUS) are also described. INTRODUCTION More than 70% of todays diagnostic radiopharmaceuticals are based on 99mTc, however the conventional supply chain for obtaining 99mTc is fragile. The aim of this work was to demonstrate reliable high yield production and processing of 99mTc with medium-energy, high-current, cyclotrons. METHODS We used two cyclotrons (TR-24, Advanced Cyclotron Systems, Inc) for irradiations with 22 MeV or 24 MeV incident energy and 400 μA current up to a maximum of 6 h. The irradiated 100Mo was dissolved using peroxide, basified using ammonium carbonate, and purified using a PEG-based solid phase extraction technique. RESULTS High-yield productions with 22 MeV (400 μA, 6 h) yielded an average isolated [99mTc]TcO4- yield of 878 GBq ± 99 GBq (23.7 Ci ± 2.7 Ci) decay corrected to EOB, n = 8 (isolated saturation yield: 4.36 ± 0.49 GBq/μA). Irradiations with 24 MeV (400 μA, 6 h) resulted in an average isolated [99mTc]TcO4- yield of 993 GBq ± 100 GBq (26.8 Ci ± 2.7 Ci) decay corrected to EOB, n = 7 (isolated saturation yield: 4.97 ± 0.50 GBq/μA). These yields corresponds to 600-700 GBq (16-19 Ci) of [99mTc]TcO4- at release (i.e. 3 hour post-EOB). For all tested batches, the QC results were within the recently published specifications in the European Pharmacopoeia. CONCLUSION Reliable near-TBq production yields for 99mTc can be obtained using medium-energy cyclotrons. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE This work presents evidence that medium-energy high-current cyclotrons can provide high yields of [99mTc]TcO4- with radionuclidic impurities levels within the specifications of the existing European Pharmacopoeia monograph, indicating that this technology can have a share in the future 99mTc supply market.