Production of the next‐generation positron nuclide zirconium‐89 (<sup>89</sup>Zr) guided by Monte Carlo simulation and its good quality for antibody labeling

Wang, Feng; Ding, Jin; Guo, Xiaoyi; Liu, Teli; Ding, Lixin; Lei, Xia; Zhu, Hua

doi:10.1002/jlcr.3888

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…[ 89 Zr]Zr-oxalate was self-produced by our laboratory using a [ 89 Y]Y (p, n) [ 89 Zr]Zr nuclear reaction; the production situation was detailed earlier. 27 [ 89 Zr]Zr-oxalate was neutralized with 2 M Na 2 CO 3 and then mixed with DFO-HuL13 in equal volume of 0.25 M HEPES buffer (pH 7.5). After incubation at 37 °C for 1 h, [ 89 Zr]Zr-DFO-HuL13 was eluted through a PD-10 column.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Construction of [⁸⁹Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Ding,

Wang,

Wang

et al. 2024

Mol. Pharmaceutics

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Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [ 89 Zr]Zr-labeled HuL13 to delineate LAG-3 + T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [ 89 Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (K d ) of [ 89 Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [ 89 Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [ 89 Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [ 89 Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [ 89 Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [ 89 Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Construction of [⁸⁹Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Ding,

Wang,

Wang

et al. 2024

Mol. Pharmaceutics

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“…To minimize nonspecific absorption, ethylenediaminetetraacetic acid was added to the solution to chelate the copper ion. 89 Zr was acquired by 12.5 MeV proton irradiation of a 89 Y foil target 23 . The foil was dissolved in hydrochloride acid, purified and enriched upon the ion exchange column, and elueted by oxalic acid to yield [ 89 Zr]Zr‐oxalate.…”

Section: Methodsmentioning

confidence: 99%

“…At least 370 MBq of radioactive product was yielded after the purification and enrichment for each radioisotope. The chemical and radiochemical purity of these products was verified through quality control as described in the previous publications 22–24 …”

Section: Methodsmentioning

confidence: 99%

“…The chemical and radiochemical purity of these products was verified through quality control as described in the previous publications. [22][23][24]…”

Section: Manufacture Of Radioisotopesmentioning

confidence: 99%

“…89 Zr was acquired by 12.5 MeV proton irradiation of a 89 Y foil target. 23 The foil was dissolved in hydrochloride acid, purified and enriched upon the ion exchange column, and elueted by oxalic acid to yield [ 89 Zr]Zr-oxalate. The pH of the solution was adjusted, and ZrCl 4 was added to minimize hydrolysis and nonspecific adsorption.…”

Section: Manufacture Of Radioisotopesmentioning

confidence: 99%

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Evaluating the impact of different positron emitters on the performance of a clinical PET/MR system

Meng

Liu

et al. 2022

Medical Physics

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The positron range and prompt gamma emission are distinctive with different positron emitters. The performance assessment of an integrated PET/MR scanner with these positron emitters is required for related applications, as the magnetic field interferes with the positron propagation. Such an assessment is to be performed on the United Imaging uPMR 790-integrated PET/MR system. Methods: The performance measurement methods were modified based on NEMA NU 2-2012, involving 18 F, 64 Cu, 68 Ga, 89 Zr, and 124 I as positron emitters. The NEMA IEC phantom was used for evaluations of image qualities. An agarose cap was wrapped around the point source for tissue-simulating spatial resolution measurement. The count rate performance was assessed with selected positron emitters. Images of a 3D-printed Derenzo phantom and representative patients were also acquired. Results:The image quality measurement showed that all five positron emitters were suitable for the PET/MR system studied. However, due to the magnetic field, the image of the point source showed an elongated comet-tail feature, which could be eliminated by a tissue-simulating cap. This effect is more obvious in 124 I and 68 Ga, due to their long positron ranges. The imaging ability with various positron emitters was further validated with the count rate assessment, the Derenzo phantom, and the clinical images. Conclusions: Different positron emitters could be effectively imaged by the PET/MR system tested. The resolution measurement strategy proposed could be applied to measure PET spatial resolution in the magnetic field.

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Next Generation of Solid Target Radionuclide Antibody Conjugates for Tumor Immuno‐Therapy

Hou,

Kong,

Yao

et al. 2024

Labelled Comp Radiopharmac

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Immune checkpoint therapy has emerged as an effective treatment option for various types of cancers. Key immune checkpoint molecules, such as cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4), programmed cell death protein 1 (PD‐1), and lymphocyte activation gene 3 (LAG‐3), have become pivotal targets in cancer immunotherapy. Antibodies designed to inhibit these molecules have demonstrated significant clinical efficacy. Nevertheless, the ability to monitor changes in the immune status of tumors and predict treatment response remains limited. Conventional methods, such as assessing lymphocytes in peripheral blood or conducting tumor biopsies, are inadequate for providing real‐time, spatial information about T‐cell distributions within heterogeneous tumors. Positron emission tomography (PET) using T‐cell specific probes represents a promising and noninvasive approach to monitor both systemic and intratumoral immune changes during treatment. This technique holds substantial clinical significance and potential utility. In this paper, we review the applications of PET probes that target immune cells in molecular imaging.

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Production of the next‐generation positron nuclide zirconium‐89 (⁸⁹Zr) guided by Monte Carlo simulation and its good quality for antibody labeling

Cited by 6 publications

References 28 publications

Construction of [⁸⁹Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Construction of [⁸⁹Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Evaluating the impact of different positron emitters on the performance of a clinical PET/MR system

Next Generation of Solid Target Radionuclide Antibody Conjugates for Tumor Immuno‐Therapy

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Production of the next‐generation positron nuclide zirconium‐89 (89Zr) guided by Monte Carlo simulation and its good quality for antibody labeling

Cited by 6 publications

References 28 publications

Construction of [89Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Construction of [89Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Evaluating the impact of different positron emitters on the performance of a clinical PET/MR system

Next Generation of Solid Target Radionuclide Antibody Conjugates for Tumor Immuno‐Therapy

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Product

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Production of the next‐generation positron nuclide zirconium‐89 (⁸⁹Zr) guided by Monte Carlo simulation and its good quality for antibody labeling

Construction of [⁸⁹Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells

Construction of [⁸⁹Zr]Zr-Labeled HuL13 for ImmunoPET Imaging of LAG-3 Checkpoint Expression on Tumor-Infiltrating T Cells