Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice

Bansal, Aditya; Sk, Sharma; Klasen, Benedikt; Rösch, Frank; Pandey, Mukesh K.

doi:10.1038/s41598-022-19953-4

Cited by 5 publications

(5 citation statements)

References 66 publications

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“…Control rats injected with unconjugated free neutralized [ 89 Zr]Zr-(oxalate) 4 showed a rapid uptake in the bone within minutes after injection, confirmed by previously published data (Figs. 2 , 3 ) [ 11 , 12 ]. The uptake in this compartment continued to increase until day 3, after which it appeared to reach saturation and remained unchanged on day 7.…”

Section: Resultsmentioning

confidence: 99%

“…Body temperature and heart rate were monitored and kept stable by heating and regulated anaesthesia during the scan. A total of 22 male Sprague Dawley rats from Javier (399 ± 64 g, 10–12 weeks) were used, divided into 4 groups; (A) control with neutralized [ 89 Zr]Zr-(oxalate) 4 (7.2 MBq, n = 1), to confirm previous reports [ 11 , 12 ]. Group (B) controls with unbound radiotracer [ 89 Zr]Zr-(oxinate) 4 (n = 4) or [ 89 Zr]Zr-DFO-NCS) (n = 4) and received 5.2 ± 0.96 MBq and 5.1 ± 1.1 MBq, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Comparative in vivo biodistribution of cells labelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS using PET

Friberger

Nilsson

et al. 2023

EJNMMI Res

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Background In vivo monitoring of cell biodistribution using positron emission tomography (PET) provides a quantitative non-invasive method to further optimize cell therapies and related new developments in the field. Our group has earlier optimized and evaluated the in vitro properties of two radiotracers,[89Zr]Zr-(oxinate)4 and [89Zr]Zr-DFO-NCS, for the radiolabelling of different cell types. Here, we performed a microPET study to assess the in vivo biodistribution of cells in rats using these two radiotracers. Human decidual stromal cells (hDSC) and rat macrophages (rMac) were radiolabelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS. Rats were intravenously injected with radiolabelled cells, and the in vivo biodistribution was monitored with microPET/CT imaging for up to day 7. Organ uptake was evaluated and presented as a percentage of injected activity per gram tissue (%IA/g) and total absorbed organ doses (mSv/MBq). Results The biodistribution in vivo showed an immediate uptake in the lungs. Thereafter, [89Zr]Zr-(oxinate)4 labelled cells migrated to the liver, while the signal from [89Zr]Zr-DFO-NCS labelled cells lingered in the lungs. The differences in the in vivo behaviour for the same cell type appeared related to the radiotracer labelling. After 24 h, [89Zr]Zr-(oxinate)4 labelled cells had over 70% higher liver uptake for both hDSC and rMac compared to [89Zr]Zr-DFO-NCS labelled cells, whereas [89Zr]Zr-DFO-NCS labelled cells showed over 60% higher uptake in the lungs compared to [89Zr]Zr-(oxinate)4 labelled cells. This difference in both lung and liver uptake continued until day 7. Dosimetry calculations showed a higher effective dose (mSv/MBq) for [89Zr]Zr-DFO-NCS compared to [89Zr]Zr-(oxinate)4, for both cell types. Although the bone uptake was higher for [89Zr]Zr-(oxinate)4 labelled cells, the prolonged uptake in the lungs contributed to a significant crossfire to bone marrow resulting in a higher bone dose. Conclusion The [89Zr]Zr-DFO-NCS labelled cells suggest a prolonged accumulation in the lungs, while [89Zr]Zr-(oxinate)4 suggests quicker clearance of the lungs followed by accumulation in the liver. Accumulation of radiolabelled cells in the liver corresponds to other cell-tracking methods. Further studies are required to determine the actual location of the [89Zr]Zr-DFO-NCS labelled cell.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Comparative in vivo biodistribution of cells labelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS using PET

Friberger

Nilsson

et al. 2023

EJNMMI Res

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“…However, previous tracking studies, including our current study, have demonstrated that most MSCs labeled with fluorescence or isotopes are primarily trapped in the lung upon intravenous infusion. [30,36] This phenomenon can be attributed to volume constraints, as human UC-MSCs cultured in vitro have a larger diameter of approximately 15-19 µm, which makes them more susceptible to being trapped in the lungs. In contrast, smaller microspheres (4-5 µm) and hematopoietic stem cells (4-12 µm) can readily traverse the pulmonary passages.…”

Section: Discussionmentioning

confidence: 99%

“…[19,22,29] The potential limitation of direct cellular radiolabeling methods is that they can only be tracked in the short term due to the temporal decay of radioactivity or the instability of the labeled radiolabel. [30] Meanwhile, these labeling techniques are unsuitable for precise and quantitative pharmacokinetic studies. Currently, the preferred quantitative approach is RT-qPCR, which allows for quantitative or semi-quantitative determination of cell numbers in specific tissues.…”

Section: Discussionmentioning

confidence: 99%

A highly sensitive and specific Homo1‐based real‐time qPCR method for quantification of human umbilical cord mesenchymal stem cells in rats

He,

Wang,

et al. 2024

Biotechnology Journal

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BackgroundOwing to the characteristics of easier access in vitro, low immunogenicity, and high plasticity, human umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) are considered as a promising cell‐based drugs for clinical application. No internationally recognized technology exists to evaluate the pharmacokinetics and distribution of cell‐based drugs in vivo.MethodsWe determined the human‐specific gene sequence, Homo1, from differential fragments Homo sapiens mitochondrion and Rattus norvegicus mitochondrion. The expression of Homo1 was utilized to determine the distribution of UC‐MSCs in the normal and diabetic nephropathy (DN) rats.ResultsWe observed a significant correlation between the number of UC‐MSCs and the expression level of Homo1. Following intravenous transplantation, the blood levels of UC‐MSCs peaked at 30 min. A large amount of intravenously injected MSCs were trapped in the lungs, but the number of them decreased rapidly after 24 h. Additionally, the distribution of UC‐MSCs in the kidneys of DN rats was significantly higher than that of normal rats.ConclusionsIn this study, we establish a highly sensitive and specific Homo1‐based real‐time quantitative PCR method to quantify the distribution of human UC‐MSCs in rats. The method provides guidelines for the safety research of cells in preclinical stages.

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“…Covalent tethering of [ 89 Zr]Zr-DBN to cells is another highly studied methodology to noninvasively track various cell types with PET. Published reports of this method demonstrate that it offers a robust and reliable approach that could be translated in humans for monitoring cell-based therapies [122][123][124][125]. Table 6 summarizes the clinical applications of 89 Zr-based radiopharmaceuticals.…”

Section: Clinical Practicementioning

confidence: 99%

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research

Sharma,

Pandey

2023

Pharmaceuticals

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The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for imaging and radionuclide therapy, it is included in this review. In regard to radionuclide therapy, both beta-minus (β−) and alpha (α)-emitting radionuclides are discussed by highlighting their production routes, targeted radiopharmaceuticals, and current clinical translation stage.

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Evaluation of different 89Zr-labeled synthons for direct labeling and tracking of white blood cells and stem cells in healthy athymic mice

Cited by 5 publications

References 66 publications

Comparative in vivo biodistribution of cells labelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS using PET

Comparative in vivo biodistribution of cells labelled with [89Zr]Zr-(oxinate)4 or [89Zr]Zr-DFO-NCS using PET

A highly sensitive and specific Homo1‐based real‐time qPCR method for quantification of human umbilical cord mesenchymal stem cells in rats

Radiometals in Imaging and Therapy: Highlighting Two Decades of Research

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