Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets

Rotsch, David A.; Brown, Matthew A.; Nolen, J.A.; Brossard, Thomas; Henning, W.; Chemerisov, Sergey; Gromov, Roman; Greene, J. P.

doi:10.1016/j.apradiso.2017.11.007

Cited by 50 publications

(35 citation statements)

References 26 publications

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“…The typical masses of impurities measured after both steps were less than 1 μg for Cr, Cu, and Ni while Fe and Zn was less than 2 μg. These data on overall recovery compare well with recent work by Rotsch et al (2018) and Domnanich et al (2017) where a 76.3% and 89.7% overall recovery was reported using branched DGA ( N , N , N ′, N ′-tetrakis-2-ethylhexyl-diglycolamide) cation-exchange resin [20, 36]. Further, the mass of Zn and Fe measured in the purified 47 Sc fraction was reduced by 60% and 45%, respectively, compared to the mass reported by Rotsch et al (2018) [20].…”

Section: Discussionsupporting

confidence: 90%

“…In the work by Rotsch et al, using a 35 MeV electron beam and capturing a larger portion of the nat Ti(γ,p) 47 Sc cross section (Fig. 1), the ratio of 46,47,48 Sc EOB activities produced were 0.01, 0.90, and 0.09 [20]. The ratio of 46,47,48 Sc EOB activities in this work using a 22 MeV electron beam were 0.01, 0.90, and 0.09.…”

Section: Discussionmentioning

confidence: 99%

“…Use of a radiator does not significantly alter the energy distribution of radiated photons, but it enhances the number of radiated photons and hence increases the number that are energetic enough to induce photonuclear reactions. Rotsch et al (2018) used nat TiO 2 targets to demonstrate a 47 Sc production rate at 35 MeV and 40 MeV of 4.25 MBq/g·kW·h and 6.92 MBq/g·kW·h, respectively, using bremsstrahlung photons [20]. Belyshev et al (2015) showed that the integrated cross section of the nat Ti(γ,p) 47 Sc reaction, using thin titanium foils of natural isotopic composition, was 110 ± 19 mb using a 55 MeV electron beam [18].…”

Section: Introductionmentioning

confidence: 99%

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Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc

et al. 2019

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Background In molecular imaging and nuclear medicine, theranostic agents that integrate radionuclide pairs are successfully being used for individualized care, which has led to rapidly growing interest in their continued development. These compounds, which are radiolabeled with one radionuclide for imaging and a chemically identical or similar radionuclide for therapy, may improve patient-specific treatment and outcomes by matching the properties of different radionuclides with a targeting vector for a particular tumor type. One proposed theranostic radionuclide is scandium-47 ( 47 Sc, T 1/2 = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, 43 Sc ( T 1/2 = 3.89 h) and 44 Sc ( T 1/2 = 3.97 h) for imaging. The aim of this study was to investigate the photonuclear production of 47 Sc via the 48 Ti(γ,p) 47 Sc reaction using an electron linear accelerator (eLINAC), separation and purification of 47 Sc, the radiolabeling of somatostatin receptor-targeting peptide DOTATOC with 47 Sc, and in vitro receptor-mediated binding of [ 47 Sc]Sc-DOTATOC in AR42J somatostatin receptor subtype two (SSTR2) expressing rat pancreatic tumor cells. Results The rate of 47 Sc production in a stack of natural titanium foils ( n = 39) was 8 × 10 7 Bq/mA·h ( n = 3). Irradiated target foils were dissolved in 2.0 M H 2 SO 4 under reflux. After dissolution, trivalent 47 Sc ions were separated from natural Ti using AG MP-50 cation exchange resin. The recovered 47 Sc was then purified using CHELEX 100 ion exchange resin. The average decay-corrected two-step 47 Sc recovery ( n = 9) was (77 ± 7)%. A radiolabeling yield of > 99.9% of [ 47 Sc]Sc-DOTATOC (0.384 mg in 0.3 mL) was achieved using 1.7 MBq of 47 Sc. Blocking studies using Octreotide illustrated receptor-mediated uptake of [ 47 Sc]Sc-DOTATOC in AR42J cells. Conclusions 47 Sc can be produced via the 48 Ti(γ,p) 47 Sc reaction and separated from natural Ti targets with a yield and radiochemical purity suitable for radiolabeling of peptides for in vitro studies. The data in this work supports the potential use of eLINACs for studies of photonuclear production of medical radionuc...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc

et al. 2019

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“…41, 42 Mamtimin et al studied the production of 47 Sc via the 48 Ti(γ,p) 47 Sc nuclear reaction by Monte Carlo simulations, 42 while Yagi et al and Rotsch et al reported preliminary experimental results obtained with enriched 48 Ti. 43, 44 Irradiation of natural Ti targets would result in many different Sc radioisotopes and, thus, low specific activity of 47 Sc. Employing enriched 48 Ti targets when irradiating with 22 MeV beam would maximize the 47 Sc production and, simultaneously, minimize the formation of other unwanted Sc radionuclides.…”

Section: Production Of Scandium and Terbium Radionuclidesmentioning

confidence: 99%

Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application

Müller

Domnanich

Umbricht

et al. 2018

The British Journal of Radiology

145

118

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Currently, different radiometals are in use for imaging and therapy in nuclear medicine: Ga andIn are examples of nuclides for positron emission tomography (PET) and single photon emission computed tomography (SPECT), respectively, while Lu andAc are used for β- and α-radionuclide therapy. The application of diagnostic and therapeutic radionuclides of the same element (radioisotopes) would utilize chemically-identical radiopharmaceuticals for imaging and subsequent treatment, thereby enabling the radiotheranostic concept. There are two elements which are of particular interest in this regard: Scandium and Terbium. Scandium presents three radioisotopes for theranostic application. Sc (T = 3.9 h) and Sc (T = 4.0 h) can both be used for PET, while Sc (T = 3.35 d) is the therapeutic match-also suitable for SPECT. Currently, Sc is most advanced in terms of production, as well as with pre-clinical investigations, and has already been employed in proof-of-concept studies in patients. Even though the production ofSc may be more challenging, it would be advantageous due to the absence of high-energetic γ-ray emission. The development of Sc is still in its infancy, however, its therapeutic potential has been demonstrated preclinically. Terbium is unique in that it represents four medically-interesting radioisotopes.Tb (T = 5.32 d) and Tb (T = 17.5 h) can be used for SPECT and PET, respectively. Both radioisotopes were produced and tested preclinically. Tb has been the first Tb isotope that was tested (asTb-DOTATOC) in a patient. Both radionuclides may be of interest for dosimetry purposes prior to the application of radiolanthanide therapy. The decay properties of Tb (T = 6.89 d) are similar to Lu, but the coemission of Auger electrons make it attractive for a combined β/Auger electron therapy, which was shown to be effective in preclinical experiments. Tb (T = 4.1 h) has been proposed for targeted α-therapy with the possibility of PET imaging. In terms of production, Tb andTb are most promising to be made available at the large quantities suitable for future clinical translation. This review article is dedicated to the production routes, the methods of separating the radioisotopes from the target material, preclinical investigations and clinical proof-of-concept studies of Sc and Tb radionuclides. The availability, challenges of production and first (pre)clinical application, as well as the potential of these novel radionuclides for future application in nuclear medicine, are discussed.

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“…Since in most cases Ti is used as a target material, a large number of radiochemical separation methods for no-carrier-added 47 Sc from products formed in the interaction of Ti with neutrons, photons and charged particles have been developed [cf. [44][45][46][47][48][49][50][51][52][53][54]. Good summaries of those methods have been given [49,50].…”

Section: Production Of 47 Scmentioning

confidence: 99%

New developments in the production of theranostic pairs of radionuclides

Qaim

Schölten

Neumaier

2018

J Radioanal Nucl Chem

132

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A brief historical background of the development of the theranostic approach in nuclear medicine is given and seven theranostic pairs of radionuclides, namely 44g Sc/ 47 Sc, 64 Cu/ 67 Cu, 83 Sr/ 90 Sr, 86 Y/ 90 Y, 124 I/ 131 I, 152 Tb/ 161 Tb and 152 Tb/ 149 Tb, are considered. The first six pairs consist of a positron and a β −-emitter whereas the seventh pair consists of a positron and an α-particle emitter. The decay properties of all those radionuclides are briefly mentioned and their production methodologies are discussed. The positron emitters 64 Cu, 86 Y and 124 I are commonly produced in sufficient quantities via the (p,n) reaction on the respective highly enriched target isotope. A clinical scale production of the positron emitter 44g Sc has been achieved via the generator route as well as via the (p,n) reaction, but further development work is necessary. The positron emitters 83 Sr and 152 Tb are under development. Among the therapeutic radionuclides, 89 Sr, 90 Y and 131 I are commercially available and 161 Tb can also be produced in sufficient quantity at a nuclear reactor. Great efforts are presently underway to produce 47 Sc and 67 Cu via neutron, photon and charged particle induced reactions. The radionuclide 149 Tb is unique because it is an α-particle emitter. The present method of production of 152 Tb and 149 Tb involves the use of the spallation process in combination with an on-line mass separator. The role of some emerging irradiation facilities in the production of special radionuclides is discussed.

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Electron linear accelerator production and purification of scandium-47 from titanium dioxide targets

Cited by 50 publications

References 26 publications

Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc

Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide 47Sc

Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application

New developments in the production of theranostic pairs of radionuclides

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