89Zr-oxine labelling and PET imaging shows lung delivery of a cell/gene cancer therapy

Abstract

AbstractPurposeMSCTRAIL is a new stem cell-based therapy for lung cancer, currently in phase I evaluation (ClinicalTrials.gov ref: NCT03298763). Biodistribution of cell therapies is rarely assessed in clinical trials, despite cell delivery to the target site often being critical to presumed mechanism of action. This preclinical study demonstrates that MSCTRAIL biodistribution dynamics can be detected non-invasively using 89Zr-oxine labelling and PET imaging, thus supporting use of this cell tracking technology in phase II evaluation.MethodsMSCTRAIL were radiolabelled with a range of 89Zr-oxine doses, and assayed for cell viability, phenotype and therapeutic efficacy post-labelling. Cell biodistribution was imaged in a mouse model of lung cancer using PET imaging and bioluminescence imaging (BLI) to confirm cell viability and location in vivo up to 1 week post-injection.ResultsMSCTRAIL retained therapeutic efficacy and MSC phenotype at doses up to and above those required for clinical imaging. The effect of 89Zr-oxine labelling on cell proliferation rate was dose and time-dependent. PET imaging showed delivery of MSCTRAIL to the lungs in a mouse model of lung cancer, with PET signal correlating with the presence of viable cells as assessed by bioluminescence imaging, ex vivo autoradiography and matched fluorescence imaging on lung tissue sections. Human dosimetry estimates were produced using simulations and preclinical biodistribution data.Conclusion89Zr-oxine labelling and PET imaging present an attractive method of evaluating the biodistribution of new cell-therapies, such as MSCTRAIL. This offers to improve understanding of mechanism of action, migration dynamics and interpatient variability of MSCTRAIL and other cell-based therapies.