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Publication Detail
Lung delivery of MSCs expressing anti-cancer protein TRAIL visualised with ⁸⁹Zr-oxine PET-CT
  • Publication Type:
    Journal article
  • Publication Sub Type:
  • Authors:
    Patrick PS, Kolluri KK, Zaw Thin M, Edwards A, Sage EK, Sanderson T, Weil BD, Dickson JC, Lythgoe MF, Lowdell M, Janes SM, Kalber TL
  • Publisher:
    BioMed Central
  • Publication date:
  • Pagination:
  • Journal:
    Stem Cell Research and Therapy
  • Volume:
  • Issue:
  • Status:
  • Print ISSN:
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 89Zr-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 89Zr-oxine and assayed for viability, phenotype, and therapeutic efficacy post-labelling. PET-CT imaging of 89Zr-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 89Zr-oxine labelling on cell proliferation rate was amount- and 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: 89Zr-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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Dept of Med Phys & Biomedical Eng
Respiratory Medicine
Department of Imaging
Div of Medicine
Research Department of Haematology
Experimental & Translational Medicine
Education (Div of Med)
Research Department of Haematology
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