In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals

Martini, Petra; Boschi, Alessandra; Cicoria, Gianfranco; Zagni, Federico; Corazza, Andrea; Uccelli, Licia; Pasquali, M.; Pupillo, Gaia; Marengo, Mario; Loriggiola, M.; Skliarova, Hanna; Mou, Liliana; Cisternino, Sara; Carturan, S.; Meléndez-Alafort, Laura; Uzunov, N.; Bello, M.; Alvarez, C. Rossi; Esposito, J.; Duatti, Adriano

doi:10.1016/j.apradiso.2018.05.033

Cited by 39 publications

(46 citation statements)

References 25 publications

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“…To determine the relative activities of 99m Tc and the other Tc isotopes, gamma spectrometry measurements were performed after purification of the CP‐ 99m Tc solution with an automated module based on methyl‐ethyl ketone‐solvent extraction system . This purification module proved highly efficient, as molybdenum and niobium radioisotope impurities coproduced during the proton irradiation of the 100 Mo‐enriched target were below the minimum detectable activity in the extracted and purified CP‐ 99m Tc solution . These results were confirmed by Gumiela et al .…”

Section: Methodssupporting

confidence: 53%

“…However, the calculated DI contribution by all Tc contaminants present in the 99m Tc‐radiopharmaceuticals injected from 6 to 12 h after the EOB still remains within the 10% limit. In addition, the 6–12 h time range after EOB required for using the Tc‐solution well matches the time necessary to carry out the separation/purification procedures, terminal sterilization, radiopharmaceutical labeling, and quality control procedure, as described by Martini et al …”

Section: Discussionmentioning

confidence: 99%

“…5,6 Experimental studies on 99m Tc production by cyclotrons using the 100 Mo(p,2n) 99m Tc reaction were initiated within the framework of the "Technetium for hospital/Laboratory of radioisotopes for medicine" (TECHN_OSP/LARAMED) research project, by the Legnaro National Laboratories at the National Institute for Nuclear Physics, Italy (LNL-INFN). 7 Results demonstrated that the direct reaction method is reliable and provides a relatively cost-effective option for the production of 99m Tc. However, gamma-ray spectrometry analyses of the resulting purified 99m Tc solutions demonstrated the presence of small quantities of several other Tc radioisotopes, such as 93 Tc, 93m Tc, 94 Tc, 94m Tc, 95 Tc, 95m Tc, 96 Tc, and 97m Tc.…”

Section: Introductionmentioning

confidence: 93%

“…Experimental studies on 99m Tc production by cyclotrons using the 100 Mo(p,2n) 99m Tc reaction were initiated within the framework of the “Technetium for hospital/Laboratory of radioisotopes for medicine” (TECHN_OSP/LARAMED) research project, by the Legnaro National Laboratories at the National Institute for Nuclear Physics, Italy (LNL‐INFN) . Results demonstrated that the direct reaction method is reliable and provides a relatively cost‐effective option for the production of 99m Tc.…”

Section: Introductionmentioning

confidence: 99%

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Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced ^99mTc

Meléndez‐Alafort

Ferro-Flores

Nardo³

et al. 2019

Medical Physics

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Purpose Technetium‐99m (99mTc) is the radioisotope most widely used in diagnostic nuclear medicine. It is readily available from 99Mo/99mTc generators as the β−decay product of the 99Mo (T½ = 66 h) parent nuclide. This latter is obtained as a fission product in nuclear reactors by neutron‐induced reactions on highly enriched uranium. Alternative production routes, such as direct reactions using proton beams on specific target materials [100Mo(p,2n)99mTc], have the potential to be both reliable and relatively cost‐effective. However, results showed that the 99mTc extracted from proton‐bombarded 100Mo‐enriched targets contains small quantities of several Tc radioisotopes (93mTc, 93Tc, 94Tc, 94mTc, 95Tc, 95mTc, 96Tc, and 97mTc). The aim of this work was to estimate the dose increase (DI) due to the contribution of Tc radioisotopes generated as impurities, after the intravenous injection of four radiopharmaceuticals prepared with cyclotron‐produced 99mTc (CP‐99mTc) using 99.05% 100Mo‐enriched metallic targets. Methods Four 99mTc radiopharmaceuticals (pertechnetate, sestamibi (MIBI), hexamethylpropylene‐amine oxime (HMPAO) and disodium etidronate (HEDP)) were considered in this study. The biokinetic models reported by the International Commission on Radiological Protection (ICRP) for each radiopharmaceutical were used to define the main source organs and to calculate the number of disintegrations per MBq that occurred in each source organ (Nsource) for each Tc radioisotope present in the CP‐99mTc solution. Then, target organ equivalent doses and effective dose were calculated for each Tc radioisotope with the OLINDA/EXM software versions 1.1 and 2.0, using the calculated Nsource values and the adult male phantom as program inputs. Total effective dose produced by all Tc isotopes impurities present in the CP‐99mTc solution was calculated using the fraction of total activity corresponding to each radioisotope and compared with the effective dose delivered by the generator‐produced 99mTc. Results In all cases, the total effective DI of CP‐99mTc radiopharmaceuticals calculated with either versions of the OLINDA software was less than 10% from 6 up to 12 h after EOB. 94mTc and 93mTc are the Tc radioisotopes with the highest concentration in the CP‐99mTc solution at EOB. However, their contribution to DI 6 h after EOB is minimal, due to their short half‐lives. The radioisotopes with the largest contribution to the effective DI are 96Tc, followed by 95Tc and 94Tc. This is due to the types of their emissions and relatively long half‐lives, although their concentration in the CP‐99mTc solution is five times lower than that of 94mTc and 93mTc at the EOB. Conclusions The increase in the radiation dose caused by other Tc radioisotopes contained in CP‐99mTc produced as described here is quite low. Even though the concentrations of the 94Tc and 95Tc radioisotopes in the CP‐99mTc solution exceed the limits established by the European Pharmacopoeia, CP‐99mTc radiopharmaceuticals could be used in routine nuclear medicine diagno...

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Section: Methodssupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced ^99mTc

Meléndez‐Alafort

Ferro-Flores

Nardo³

et al. 2019

Medical Physics

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“…The automatable module developed and properly optimized for this project (Figure 8) involves five main steps: (1) dissolution of the irradiated target and basification of the solution; (2) solvent extraction of pertechnetate with MEK from the aqueous alkaline solution; (3) separation of the MEK phase, containing pertechnetate, from aqueous solution containing molybdate and by-products; (4) purification of the extracted pertechnetate by column chromatography with a silica and an alumina cartridges and finally; (5) elution of sodium pertechnetate [ 99m Tc]NaTcO 4 from the alumina column with saline [26,27,28]. The dissolution, extraction and purification processes were performed the day after sample irradiation to achieve the equilibrium between 99m Tc and the parent nuclide 99 Mo.…”

Section: Methodsmentioning

confidence: 99%

14 MeV Neutrons for 99Mo/99mTc Production: Experiments, Simulations and Perspectives

et al. 2018

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Background: the gamma-emitting radionuclide Technetium-99m (99mTc) is still the workhorse of Single Photon Emission Computed Tomography (SPECT) as it is used worldwide for the diagnosis of a variety of phatological conditions. 99mTc is obtained from 99Mo/99mTc generators as pertechnetate ion, which is the ubiquitous starting material for the preparation of 99mTc radiopharmaceuticals. 99Mo in such generators is currently produced in nuclear fission reactors as a by-product of 235U fission. Here we investigated an alternative route for the production of 99Mo by irradiating a natural metallic molybdenum powder using a 14-MeV accelerator-driven neutron source. Methods: after irradiation, an efficient isolation and purification of the final 99mTc-pertechnetate was carried out by means of solvent extraction. Monte Carlo simulations allowed reliable predictions of 99Mo production rates for a newly designed 14-MeV neutron source (New Sorgentina Fusion Source). Results: in traceable metrological conditions, a level of radionuclidic purity consistent with accepted pharmaceutical quality standards, was achieved. Conclusions: we showed that this source, featuring a nominal neutron emission rate of about 1015 s−1, may potentially supply an appreciable fraction of the current 99Mo global demand. This study highlights that a robust and viable solution, alternative to nuclear fission reactors, can be accomplished to secure the long-term supply of 99Mo.

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A semi-automated module for the separation and purification of 99mTc from simulated molybdenum target

Koźmiński

Gumiela

Walczak

et al. 2021

J Radioanal Nucl Chem

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A semi-automated purification module for the cyclic separation of 99mTc was designed for production of [99mTc]TcO4– from γ irradiated 100Mo target. The separation process was carried out by using a 3-column purification system and the final product, [99mTc]TcO4–, was obtained in a total volume of 7 mL. To confirm proper separation achieved for 99mTc, a radio-labeling procedure using DTPA chelator was performed. The radiochemical purity was higher than 95%, which meets the strict radiopharmaceutical requirements. The yielded 99mTc can be separated with high efficiency from Mo in a quick and repeated way. Loss of 99mTc radioactivity during such a three-column separation process was not larger than 10%.

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In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals

Cited by 39 publications

References 25 publications

Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced ^99mTc

Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced ^99mTc

14 MeV Neutrons for 99Mo/99mTc Production: Experiments, Simulations and Perspectives

A semi-automated module for the separation and purification of 99mTc from simulated molybdenum target

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In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals

Cited by 39 publications

References 25 publications

Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced 99mTc

Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced 99mTc

14 MeV Neutrons for 99Mo/99mTc Production: Experiments, Simulations and Perspectives

A semi-automated module for the separation and purification of 99mTc from simulated molybdenum target

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Product

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Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced ^99mTc

Internal radiation dose assessment of radiopharmaceuticals prepared with cyclotron‐produced ^99mTc