Cyclotron Production Of 99mTc Research Articles

Analysis of radioactive waste generated during the cyclotron production of 99mTc

Past and prospective shortages of medical radioisotopes have driven recent developments in the direct production of 99mTc via the 100Mo(p,2n)99mTc reaction. The cyclotron-based production method has been shown to successfully produce 99mTc, however trace impurities present in the enriched molybdenum target can also lead to the unintended creation of other radioisotopes which constitute waste. The isotopic composition of the waste has to be investigated in order to determine how it can be handled, transported and safely stored. In this article, we report which waste radioisotopes are created alongside 99mTc during target irradiation. Results are based on the gamma spectroscopy of waste produced. Significant complexities in the emission spectra made automated identification of radioisotopes inaccurate; complexities were resolved using a manual radioisotope identification procedure. The impact of target composition, integrated beam current and duration of target irradiation on the waste produced was studied. Results indicate that an average of 0.059 ± 0.003 GBq of waste is generated per 1 GBq of 99mTc produced. Two-thirds of the total waste activity produced was attributed to 99Mo (T1/2 = 66 h) alone, while a total of fifty radioisotopes were found in the waste. Long-lived isotopes (T1/2 > 2 months) constituted only 1% of the total waste activity at end of beam (EOB). In conclusion, it was determined that the waste generated during cyclotron-based 99mTc production was acceptably low for routine clinical production.

Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.

Cyclotron production of 99mTc is a promising route to supply 99mTc radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99mTc produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required. Thick 100Mo (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate 99mTc was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using γ-ray spectrometry. The internal radiation dose for 99mTc-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms. Extracted sodium pertechnetate 99mTc met all provisional quality standards. The formulated solution for injection had a pH of 5.0-5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of 99mTc produced with 99.03% enriched 100Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of 99mTc produced with 99.815% enriched 100Mo was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to 99mTc without any radionuclidic impurities was below 10% for sodium pertechnetate 99mTc produced from 99.03% 100Mo if injected up to 6 h after the EOB. For 99.815% 100Mo, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced 99mTc were equivalent to those obtained with 99mTc eluted from a conventional generator. Clinical-grade sodium pertechnetate 99mTc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99mTc in routine clinical practice.

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced 99mTc yields

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. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional 99mTc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity 99mTc. However, variations in proton beam currents and the thickness and isotopic composition of enriched 100Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute 99mTc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including 100Mo target thicknesses and proton beam currents, and reproducibility of absolute 99mTc yields (defined as the end of bombardment (EOB) 99mTc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB 99mTc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in 99mTc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of 99mTc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced 99mTc.

Large-scale cyclotron production of 99mTc

Large-scale cyclotron production of 99mTc

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

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. 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. 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. These findings suggest that the cyclotron production of (99m)Tc may be a feasible alternative to the current reactor-based production strategy.