On-cartridge preparation and evaluation of 68Ga-, 89Zr- and 64Cu-precursors for cell radiolabelling

Sočan, Aljaž; Petřík, Miloš; Peitl, Petra Kolenc; Krošelj, Marko; Rangger, Christine; Nový, Zbyněk; Švajger, Urban; Gmeiner, Tanja; Decristoforo, Clemens

doi:10.1016/j.nucmedbio.2019.04.001

Cited by 19 publications

(21 citation statements)

References 37 publications

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“…Several parameters were investigated to improve the radiochemical conversion (RCC) from the original protocol [16,[24][25][26], as well as to minimise the timeframe of radioactive exposure. See supplementary.…”

Section: Optimization Of [ 89 Zr]zr-oxine Synthesismentioning

confidence: 99%

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Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

et al. 2021

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Background There is a need to better characterise cell-based therapies in preclinical models to help facilitate their translation to humans. Long-term high-resolution tracking of the cells in vivo is often impossible due to unreliable methods. Radiolabelling of cells has the advantage of being able to reveal cellular kinetics in vivo over time. This study aimed to optimise the synthesis of the radiotracers [89Zr]Zr-oxine (8-hydroxyquinoline) and [89Zr]Zr-DFO-NCS (p-SCN-Bn-Deferoxamine) and to perform a direct comparison of the cell labelling efficiency using these radiotracers. Procedures Several parameters, such as buffers, pH, labelling time and temperature, were investigated to optimise the synthesis of [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS in order to reach a radiochemical conversion (RCC) of >95 % without purification. Radio-instant thin-layer chromatography (iTLC) and radio high-performance liquid chromatography (radio-HPLC) were used to determine the RCC. Cells were labelled with [89Zr]Zr-oxine or [89Zr]Zr-DFO-NCS. The cellular retention of 89Zr and the labelling impact was determined by analysing the cellular functions, such as viability, proliferation, phagocytotic ability and phenotypic immunostaining. Results The optimised synthesis of [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS resulted in straightforward protocols not requiring additional purification. [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS were synthesised with an average RCC of 98.4 % (n = 16) and 98.0 % (n = 13), respectively. Cell labelling efficiencies were 63.9 % (n = 35) and 70.2 % (n = 30), respectively. 89Zr labelling neither significantly affected the cell viability (cell viability loss was in the range of 1–8 % compared to its corresponding non-labelled cells, P value > 0.05) nor the cells’ proliferation rate. The phenotype of human decidual stromal cells (hDSC) and phagocytic function of rat bone-marrow-derived macrophages (rMac) was somewhat affected by radiolabelling. Conclusions Our study demonstrates that [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS are equally effective in cell labelling. However, [89Zr]Zr-oxine was superior to [89Zr]Zr-DFO-NCS with regard to long-term stability, cellular retention, minimal variation between cell types and cell labelling efficiency.

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Section: Optimization Of [ 89 Zr]zr-oxine Synthesismentioning

confidence: 99%

“…1), which may help facilitate clinical translation. The currently available protocols for [ 89 Zr]Zr-oxine synthesis are characterised by a low overall radiochemical yield (RCY) and include cumbersome steps such as buffer exchange, chloroform extractions, evaporations and the usage of several buffers in the synthesis [16,[23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

et al. 2021

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“…The radiolabeling of oxine with 89 Zr for use as a radiopharmaceutical for cell labeling is not a new concept. Several authors have carried out cell radiolabeling with a high level of success [10][11][12][16][17][18][19] and have conducted preclinical studies. Here we expand the literature by describing 89 Zr WBC labeling suitable for human use.…”

Section: Discussionmentioning

confidence: 99%

“…Zirconium-89 is a β + -emitter radioisotope that yields high spatial resolution on PET and, consequently, potentially improved image quality. Its long physical half-life (t½ = 3.27 days) matches the biological half-life of macromolecules such as antibodies and intact cells and allows for imaging at later time points compared to other radioisotopes, 18 F and 68 Ga. 13,14 To date, there is no data available regarding the production of [ 89 Zr]Oxinate 4 for human use. This may be due in part to the stringent criteria that radiopharmaceuticals intended for human use must meet in order to comply with United States Pharmacopeia (USP) <823>.…”

Section: Introductionmentioning

confidence: 99%

Production of [⁸⁹Zr]Oxinate₄ and cell radiolabeling for human use

Massicano

Bartels

Jeffers

et al. 2021

Labelled Comp Radiopharmac

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[89Zr]Oxinate4 is a Positron Emission Tomography (PET) tracer for cell radiolabeling that can enable imaging techniques to help better understand cell trafficking in various diseases. Although several groups have synthetized this compound for use in preclinical studies, there is no available data regarding the production of [89Zr]Oxinate4 for human use. In this report, we describe the detailed production of [89Zr]Oxinate4 under USP <823> and autologous leukocyte radiolabeling under USP <797>. The final product presented high radiochemical purity and stability at 24 h post synthesis (>99%) and passed in all quality control assays required for clinical use. [89Zr]Oxinate4 did not compromise the white blood cells viability and did not show considerable cellular efflux up to 3 h post labeling. The translation of this technique into human use can provide insight into several disease mechanisms since [89Zr]Oxinate4 has the potential to label any cell subset of interest.

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“…The positron nuclide 18 F has the advantages of good image quality and suitable half-life (109.8 min) for commercialization and transportation compared with other positron nuclides. Moreover, the resulting carbon-fluorine bonds generally have reasonable stability, which could be advantageous for BPI (22). However, there are only a few 18 F-labeled RBCs reported as BPI agents partially due to the limitation of the labeling method (23).…”

Section: Introductionmentioning

confidence: 99%

18F-PEG1-Vinyl Sulfone-Labeled Red Blood Cells as Positron Emission Tomography Agent to Image Intra-Abdominal Bleeding

Zhang

Wang

et al. 2021

Front. Med.

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18F-Labeled blood pool agents (BPAs) have attracted great attention for identifying bleeding sites. However, many BPAs are not sufficiently evaluated partially due to the limitations of labeling methods. In our previous work, we noticed that 18F-PEG1-vinyl sulfone (18F-VS) could efficiently label red blood cells (RBCs) ex vivo and in situ. However, its application as BPA is not fully evaluated. In this study, we systematically explored the feasibility of using 18F-VS-labeled RBCs as a positron emission tomography (PET) BPA for intra-abdominal bleeding diagnosis. In brief, we first optimized the labeling conditions, which lead to an 80% labeling yield of RBCs after incubating with 18F-VS in phosphate-buffered saline (PBS) at 37°C for 20 min. 18F-VS-labeled RBCs were found to be stable in vitro, which could simplify its transportation/storage for in vivo applications. In normal rat PET study, the cardiovascular system could be clearly imaged up to 5 h post injection (p.i.). An intra-abdominal hemorrhage rat model demonstrated that the 18F-VS-labeled RBCs clearly showed the dynamic changes of extravascular radioactivity due to intra-abdominal hemorrhage. Validation in the model of gastrointestinal bleeding clearly demonstrated the great potential of using 18F-VS-labeled RBCs as a BPA, which could be further evaluated in future studies.

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On-cartridge preparation and evaluation of 68Ga-, 89Zr- and 64Cu-precursors for cell radiolabelling

Cited by 19 publications

References 37 publications

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

Production of [⁸⁹Zr]Oxinate₄ and cell radiolabeling for human use

18F-PEG1-Vinyl Sulfone-Labeled Red Blood Cells as Positron Emission Tomography Agent to Image Intra-Abdominal Bleeding

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On-cartridge preparation and evaluation of 68Ga-, 89Zr- and 64Cu-precursors for cell radiolabelling

Cited by 19 publications

References 37 publications

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

Optimisation of the Synthesis and Cell Labelling Conditions for [89Zr]Zr-oxine and [89Zr]Zr-DFO-NCS: a Direct In Vitro Comparison in Cell Types with Distinct Therapeutic Applications

Production of [89Zr]Oxinate4 and cell radiolabeling for human use

18F-PEG1-Vinyl Sulfone-Labeled Red Blood Cells as Positron Emission Tomography Agent to Image Intra-Abdominal Bleeding

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Product

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Production of [⁸⁹Zr]Oxinate₄ and cell radiolabeling for human use