Bone marrow cell homing to sites of acute tibial fracture: 89Zr-oxine cell labeling with positron emission tomographic imaging in a mouse model

Asiedu, Kingsley O.; Ferdousi, Munira; Ton, Phuongnga T.; Adler, S. S.; Choyke, Peter L.; Sato, Noriko

doi:10.1186/s13550-018-0463-8

Cited by 28 publications

(31 citation statements)

References 36 publications

(45 reference statements)

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“…With the introduction of total-body clinical PET scanners, this is set to increase by a further~40fold, reducing scan times and radioactive doses for patients and thus increasing the practicality of whole-body cell tracking in the clinic [19]. A handful of preclinical studies have so far shown the worth of 89 Zr-oxine in tracking cell therapies in mouse models, including T cells [20,21], dendritic cells, NK cells [17], and bone marrow cells [22,23]. However, 89 Zr-oxine toxicity is dependent on the amount used for labelling and varies between cell types, requiring individual evaluation with each prospective cell therapy prior to clinical implementation.…”

Section: Introductionmentioning

confidence: 99%

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

et al. 2020

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Background: MSCTRAIL is a cell-based therapy consisting of human allogeneic umbilical cord-derived MSCs genetically modified to express the anti-cancer protein TRAIL. Though cell-based therapies are typically designed with a target tissue in mind, delivery is rarely assessed due to a lack of translatable non-invasive imaging approaches. In this preclinical study, we demonstrate 89 Zr-oxine labelling and PET-CT imaging as a potential clinical solution for non-invasively tracking MSCTRAIL biodistribution. Future implementation of this technique should improve our understanding of MSCTRAIL during its evaluation as a therapy for metastatic lung adenocarcinoma. Methods: MSCTRAIL were radiolabelled with 89 Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89 Zr-oxine-labelled MSCTRAIL was performed in a mouse model of lung cancer following intravenous injection, and biodistribution was confirmed ex vivo. Results: MSCTRAIL retained the therapeutic efficacy and MSC phenotype in vitro at labelling amounts up to and above those required for clinical imaging. The effect of 89 Zr-oxine labelling on cell proliferation rate was amountand time-dependent. PET-CT imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer up to 1 week post-injection, validated by in vivo bioluminescence imaging, autoradiography, and fluorescence imaging on tissue sections. Conclusions: 89 Zr-oxine labelling and PET-CT imaging present a potential method of evaluating the biodistribution of new cell therapies in patients, including MSCTRAIL. This offers to improve understanding of cell therapies, including mechanism of action, migration dynamics, and inter-patient variability.

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Section: Introductionmentioning

confidence: 99%

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

et al. 2020

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“…In a bone fracture model, 89 Zr-oxine PET further shows the mobilization of pre-transferred 89 Zr-labeled bone marrow cells from pre-distributed organs (bone marrow, spleen, and liver) to a site of fracture within 1 day of injury [63]. This re-distribution of pre-distributed bone marrow cells is also impaired by plerixafor treatment [63]. These reports indicate that 89 Zr-oxine labeling of highly radiosensitive bone marrow could be performed with minimum effect on functionality of the cells.…”

Section: Monitoring Of Transferred Cells Using 89 Zr-oxine Pet In Moumentioning

confidence: 96%

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

Kurebayashi¹,

Choyke²,

Sato³

2021

Nanotheranostics

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With the rapid development of anti-cancer cell-based therapies, such as adoptive T cell therapies using tumor-infiltrating T cells, T cell receptor transduced T cells, and chimeric antigen receptor T cells, there has been a growing interest in imaging technologies to non-invasively track transferred cells in vivo. Cell tracking using ex vivo cell labeling with positron emitting radioisotopes for positron emission tomography (PET) imaging has potential advantages over single-photon emitting radioisotopes. These advantages include intrinsically higher resolution, higher sensitivity, and higher signal-to-background ratios. Here, we review the current status of recently developed Zirconium-89 (89 Zr)-oxine ex vivo cell labeling with PET imaging focusing on its applications and future perspectives. Labeling of cells with 89 Zr-oxine is completed in a series of relatively simple steps, and its low radioactivity doses required for imaging does not interfere with the proliferation or function of the labeled immune cells. Preclinical studies have revealed that 89 Zr-oxine PET allows high-resolution in vivo tracking of labeled cells for 1-2 weeks after cell transfer both in mice and non-human primates. These results provide a strong rationale for the clinical translation of 89 Zr-oxine PET-based imaging of cell-based therapy.

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“… 42 Adiponectin directly 40 and through increasing S1P in the serum, 17 leads to increased osteoblast progenitor migration into the circulation and to bone in health, 48 which is enhanced during injury. 41 , 116 , 117 In contrast, S1P chemorepels osteoclast progenitors and osteoclasts, 51 leading to decreased migration to damaged sites. This ultimately maintains the balance between resorption (red) and formation (green) to ensure structured bone repair …”

Section: Regulator Of Osteoblast and Osteoclast Progenitor Migrationmentioning

confidence: 99%

Adiponectin signalling in bone homeostasis, with age and in disease

et al. 2021

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Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance. Within the bone, osteoblasts and osteoclasts express the adiponectin receptors, however, there are conflicting reports on the effects of adiponectin on bone formation and turnover. Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro: with increased osteoblast differentiation and activity, alongside lower levels of osteoclastogenesis. However, human studies often demonstrate an inverse relationship between adiponectin concentration and bone activity. Moreover, the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional consequences. As such, we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health, with age and in disease. In this review, we explore our current understanding of adiponectin bioactivity in the bone; the significance of its different isoforms; and how adiponectin biology is altered in disease. Ultimately, furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological (lifestyle) interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing, following injury or in disease.

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Bone marrow cell homing to sites of acute tibial fracture: 89Zr-oxine cell labeling with positron emission tomographic imaging in a mouse model

Cited by 28 publications

References 36 publications

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography

Adiponectin signalling in bone homeostasis, with age and in disease

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Bone marrow cell homing to sites of acute tibial fracture: 89Zr-oxine cell labeling with positron emission tomographic imaging in a mouse model

Cited by 28 publications

References 36 publications

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with 89Zr-oxine PET-CT

Imaging of cell-based therapy using 89Zr-oxine ex vivo cell labeling for positron emission tomography

Adiponectin signalling in bone homeostasis, with age and in disease

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Imaging of cell-based therapy using ⁸⁹Zr-oxine ex vivo cell labeling for positron emission tomography