Peter J. Gawne, Theranostics, 2020
The encapsulation of glucocorticoids (GCs) into long-circulating liposomes (LCLs) is a proven strategy to reduce the side effects of glucocorticoids and improve the treatment of inflammatory diseases, such as rheumatoid arthritis.
With the aim of supporting the development of GC-loaded LCLs, and potentially predict patient response to therapy clinically, in this study, a direct PET imaging radiolabelling approach was evaluated for GC-LCLs in an animal model of human inflammatory arthritis.
A preformed PEGylated liposomal methylprednisolone hemisuccinate (NSSL-MPS) nanomedicine was radiolabelled using 89Zr(oxinate)4, characterised and tracked in vivo using nanoScan PET/CT in a mouse model of inflammatory arthritis (STA) and non-inflamed controls. Histology and joint size measurements were used to confirm inflammation. The biodistribution of 89Zr-NSSL-MPS was compared to that of free 89Zr in the same model.
PET/CT imaging of 89Zr-NSSL-MPS showed high uptake at inflamed joints and low activity in the non-inflamed joints. Clear correlation between joint swelling and high 89Zr-NSSL-MPS uptake was observed. STA mice receiving a therapeutic dose of NSSL-MPS showed a reduction in inflammation at the time points used for the PET/CT imaging compared with the control group.
PET imaging was used for the first time to track a liposomal glucocorticoid, showing high uptake at inflamed sites and a good correlation with the degree of inflammation. A subsequent therapeutic response matching imaging time points in the same model demonstrated the potential of this radiolabeling method as a theranostic tool for the prediction of therapeutic response in the treatment of inflammatory diseases.
Results from nanoScan PET/CT
Inflammatory arthritis was induced using the K/BxN serum transfer arthritis (STA) model: 9-week old female C57Bl/6J mice were injected i.p. with arthritogenic serum (150 μL) on day 0, followed by an additional injection on day 2. Control mice were injected i.p with non-arthritogenic serum. The size of the joints were monitored to track the progress of the disease.
On day 7, 89Zr-NSSL-MPS (1.3MBq) was injected i.v. into the mice. PET/CT imaging was performed 2 days later for 60 min on nanoScan PET/CT. All data sets were reconstructed using a Monte Carlo based full 3D iterative algorithm (Tera-Tomo, Mediso Medical Imaging Systems, Budapest, Hungary). Decay correction to time of injection was applied.
Having made the correlation between 89Zr-NSSL-MPS uptake levels and inflammation in joints in arthritic mice, the therapeutic efficacy of NSSL-MPS was tested: 7 days after induction of STA, a therapeutic dose of NSSL-MPS was administered and the total visual inflammation score was determined.
Immediately after the PET/CT imaging, mice were sacrificed by cervical dislocation under anaesthesia, and the organs of interest were dissected. Each sample was then weighed and counted with a γ counter.
Full article on thno.org
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