Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

Mikołajczak, Renata; Huclier‐Markai, Sandrine; Alliot, Cyrille; Haddad, Férid; Szikra, Dezső; Forgács, Viktória; Garnuszek, Piotr

doi:10.1186/s41181-021-00131-2

Cited by 37 publications

(33 citation statements)

References 109 publications

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“…On the other hand, this γ-co-emission of 44 Sc could be relevant to a new imaging approach based on the three-dimensional measurement of the emitter location using β + /γ emitters [8,12]. 44 Sc can be obtained by both using a cyclotron from a calcium target [13][14][15] and using a radionuclide generator from the parent radionuclide 44 Ti (T 1 2 = 60.0 a [1]). Regarding the potentially wide clinical application of 44 Sc (up to the current level of 68 Ga use), the cyclotron method of production is preferable, considering the cross sections and yields of 44 Ca(p,n) 44 Sc and 45 Sc(p,2n) 44 Ti→ 44 Sc reactions [16].…”

Section: Introductionmentioning

confidence: 99%

Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis

2021

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Today, 44Sc is an attractive radionuclide for molecular imaging with PET. In this work, we evaluated a 44Ti/44Sc radionuclide generator based on TEVA resin as a source of 44Sc. The generator prototype (5 MBq) exhibits high 44Ti retention and stable yield of 44Sc (91 ± 6 %) in 1 mL of eluate (20 bed volumes, eluent—0.1 M oxalic acid/0.2 M HCl) during one year of monitoring (more than 120 elutions). The breakthrough of 44Ti did not exceed 1.5 × 10−5% (average value was 6.5 × 10−6%). Post-processing of the eluate for further use in radiopharmaceutical synthesis was proposed. The post-processing procedure using a combination of Presep® PolyChelate and TK221 resins made it possible to obtain 44Sc-radioconjugates with high labeling yield (≥95%) while using small precursor amounts (5 nmol). The proposed method takes no more than 15 min and provides ≥90% yield relative to the 44Sc activity eluted from the generator. The labeling efficiency was demonstrated on the example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T synthesis. Some superiority of PSMA-I&T over PSMA-617 in terms of 44Sc labeling efficiency was demonstrated (likely due to presence of DOTAGA chelator in the precursor structure). It was also shown that microwave heating of the reaction mixture considerably shortened the reaction time and improved radiolabeling yield and reproducibility of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T synthesis.

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Section: Introductionmentioning

confidence: 99%

Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis

2021

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“…Radionuclides of the same element allowed the preparation of chemically identical radiopharmaceuticals for diagnosis and therapy, enabling the concept of radiotheragnostics in the truest sense [ 46 ]. In this regard, scandium and terbium are of particular interest, as they present several radioisotopes which may be of value for clinical translation [ 46 , 47 , 48 ].…”

Section: Radionuclide Developmentmentioning

confidence: 99%

New Radionuclides and Technological Advances in SPECT and PET Scanners

Meulen

Strobel

Lima

2021

Cancers

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Developments throughout the history of nuclear medicine have involved improvements in both instrumentation and radionuclides, which have been intertwined. Instrumentation developments always occurred during the search to improving devices’ sensitivity and included advances in detector technology (with the introduction of cadmium zinc telluride and digital Positron Emission Tomography—PET-devices with silicon photomultipliers), design (total body PET) and configuration (ring-shaped, Single-Photon Emission Computed Tomography (SPECT), Compton camera). In the field of radionuclide development, we observed the continual changing of clinically used radionuclides, which is sometimes influenced by instrumentation technology but also driven by availability, patient safety and clinical questions. Some areas, such as tumour imaging, have faced challenges when changing radionuclides based on availability, when this produced undesirable clinical findings with the introduction of unclear focal uptakes and unspecific uptakes. On the other end of spectrum, further developments of PET technology have seen a resurgence in its use in nuclear cardiology, with rubidium-82 from strontium-82/rubidium-82 generators being the radionuclide of choice, moving away from SPECT nuclides thallium-201 and technetium-99m. These continuing improvements in both instrumentation and radionuclide development have helped the growth of nuclear medicine and its importance in the ever-evolving range of patient care options.

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“…. 6) the maximum and the mean recovery coefficients (RC) were obtained as follows: RC j,X , (%) = a c,j,X A c,sph × 100 (5) where A c , sph is the expected activity concentration in the spheres, a c,j,X is the measured activity concentration for a given spherical insert (j) for either the mean and the maximum evaluations (X). Calculated RC max and RC mean values were compared with reference values provided by the EANM/EARL accreditation protocol for F-18 PET [11,15].…”

Section: Recovery Coefficientsmentioning

confidence: 99%

“…[ 18 F]fluoro-deoxy-glucose ([ 18 F]FDG) is still predominant in PET imaging, but there is large interest in the development of further radionuclides to benefit from more favorable decay characteristics to match specific applications. In this regard, the availability, transport, dosimetry, and safety are critical aspects to be addressed [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

et al. 2021

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Scandium-44 has been proposed as a valuable radionuclide for Positron Emission Tomography (PET). Recently, scandium-43 was introduced as a more favorable option, as it does not emit high-energy γ-radiation; however, its currently employed production method results in a mixture of scandium-43 and scandium-44. The interest in new radionuclides for diagnostic nuclear medicine critically depends on the option for image-based quantification. We aimed to evaluate and compare the quantitative capabilities of scandium-43/scandium-44 in a commercial PET/CT device with respect to more conventional clinical radionuclides (fluorine-18 and gallium-68). With this purpose, we characterized and compared quantitative PET data from a mixture of scandium-43/scandium-44 (~68% scandium-43), scandium-44, fluorine-18 and gallium-68, respectively. A NEMA image-quality phantom was filled with the different radionuclides using clinical-relevant lesion-to-background activity concentration ratios; images were acquired in a Siemens Biograph Vision PET/CT. Quantitative accuracy with scandium-43/scandium-44 in the phantom’s background was within 9%, which is in agreement with fluorine-18-based PET standards. Coefficient of variance (COV) was 6.32% and signal recovery in the lesions provided RCmax (recovery coefficient) values of 0.66, 0.90, 1.03, 1.04, 1.12 and 1.11 for lesions of 10-, 13-, 17-, 22-, 28- and 37-mm diameter, respectively. These results are in agreement with EARL reference values for fluorine-18 PET. The results in this work showed that accurate quantitative scandium-43/44 PET/CT is achievable in commercial devices. This may promote the future introduction of scandium-43/44-labelled radiopharmaceuticals into clinical use.

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Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements

Cited by 37 publications

References 109 publications

Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis

Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis

New Radionuclides and Technological Advances in SPECT and PET Scanners

Fifty Shades of Scandium: Comparative Study of PET Capabilities Using Sc-43 and Sc-44 with Respect to Conventional Clinical Radionuclides

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