Journal
THERANOSTICS
Volume 10, Issue 9, Pages 3867-3879Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.40403
Keywords
Positron Emission Tomography; Nanomedicine; In vivo Liposome Imaging; Personalised Nanomedicine; Rheumatoid Arthritis
Categories
Funding
- King's College London & Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1]
- The Rosetrees Trust [CM606]
- GlaxoSmithKline plc
- EPSRC [EP/R045046/1, EP/S032789/1]
- UCL Comprehensive Cancer Imaging Centre - CRUK
- KCL Comprehensive Cancer Imaging Centre - CRUK
- EPSRC
- MRC (England)
- DoH (England)
- Wellcome Trust
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London
- Engineering and Physical Sciences Research Council [EP/R045046/1, EP/S032789/1] Funding Source: researchfish
- EPSRC [EP/R045046/1, EP/S032789/1] Funding Source: UKRI
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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 (RA). With the aim of supporting the development of GC-loaded LCLs, and potentially predict patient response to therapy clinically, we evaluated a direct PET imaging radiolabelling approach for preformed GC-LCLs in an animal model of human inflammatory arthritis. Methods: A preformed PEGylated liposomal methylprednisolone hemisuccinate (NSSL-MPS) nanomedicine was radiolabelled using [Zr-89]Zr(oxinate) 4 (Zr-89-oxine), characterised and tracked in vivo using PET imaging in a K/BxN serum-transfer arthritis (STA) mouse model of inflammatory arthritis and non-inflamed controls. Histology and joint size measurements were used to confirm inflammation. The biodistribution of Zr-89-NSSL-MPS was compared to that of free Zr-89 in the same model. A therapeutic study using NSSL-MPS using the same time points as the PET/CT imaging was carried out. Results: The radiolabelling efficiency of NSSL-MPS with [Zr-89]Zr(oxinate) 4 was 69 +/- 8 %. PET/CT imaging of Zr-89-NSSL-MPS showed high uptake (3.6 +/- 1.5 % ID; 17.4 +/- 9.3 % ID/mL) at inflamed joints, with low activity present in non-inflamed joints (0.5 +/- 0.1 % ID; 2.7 +/- 1.1 % ID/mL). Importantly, a clear correlation between joint swelling and high 89Zr-NSSL-MPS uptake was observed, which was not observed with free Zr-89. 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. Conclusions: PET imaging was used for the first time to track a liposomal glucocorticoid, showing high uptake at visible and occult 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 with NSSL-MPS and similar nanomedicines - in the treatment of inflammatory diseases
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