ISSN: 1838-7640Theranostics
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Theranostics 2020; 10(9):3867-3879. doi:10.7150/thno.40403 This issue Cite
Research Paper
PET Imaging of Liposomal Glucocorticoids using 89Zr-oxine: Theranostic Applications in Inflammatory Arthritis
1. School of Imaging Sciences & Biomedical Engineering, King's College London, St. Thomas' Hospital, London, SE1 7EH, UK.
2. Centre for Inflammation Biology and Cancer Immunology, King's College London, New Hunt's House, London, SE1 1UL, UK.
3. Laboratory of Membrane and Liposome Research, Department of Biochemistry,Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
4. Department of Chemistry, MSRH, Imperial College London, White City Campus, W12 0BZ, London, UK.
5. London Centre for Nanotechnology, King's College London, Strand Campus, London, WC2R 2LS, United Kingdom, UK.
*These authors contributed equally to this work.
Citation:
Gawne PJ, Clarke F, Turjeman K, Cope AP, Long NJ, Barenholz Y, Terry SYA, de Rosales RTM. PET Imaging of Liposomal Glucocorticoids using 89Zr-oxine: Theranostic Applications in Inflammatory Arthritis. Theranostics 2020; 10(9):3867-3879. doi:10.7150/thno.40403. https://www.thno.org/v10p3867.htm
Other stylesAbstract
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 [89Zr]Zr(oxinate)4 (89Zr-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 89Zr-NSSL-MPS was compared to that of free 89Zr 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 [89Zr]Zr(oxinate)4 was 69 ± 8 %. PET/CT imaging of 89Zr-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 89Zr. 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
Keywords: Positron Emission Tomography, Nanomedicine, In vivo Liposome Imaging, Personalised Nanomedicine, Rheumatoid Arthritis
Citation styles
APA
Gawne, P.J., Clarke, F., Turjeman, K., Cope, A.P., Long, N.J., Barenholz, Y., Terry, S.Y.A., de Rosales, R.T.M. (2020). PET Imaging of Liposomal Glucocorticoids using 89Zr-oxine: Theranostic Applications in Inflammatory Arthritis. Theranostics, 10(9), 3867-3879. https://doi.org/10.7150/thno.40403.
ACS
Gawne, P.J.; Clarke, F.; Turjeman, K.; Cope, A.P.; Long, N.J.; Barenholz, Y.; Terry, S.Y.A.; de Rosales, R.T.M. PET Imaging of Liposomal Glucocorticoids using 89Zr-oxine: Theranostic Applications in Inflammatory Arthritis. Theranostics 2020, 10 (9), 3867-3879. DOI: 10.7150/thno.40403.
NLM
Gawne PJ, Clarke F, Turjeman K, Cope AP, Long NJ, Barenholz Y, Terry SYA, de Rosales RTM. PET Imaging of Liposomal Glucocorticoids using 89Zr-oxine: Theranostic Applications in Inflammatory Arthritis. Theranostics 2020; 10(9):3867-3879. doi:10.7150/thno.40403. https://www.thno.org/v10p3867.htm
CSE
Gawne PJ, Clarke F, Turjeman K, Cope AP, Long NJ, Barenholz Y, Terry SYA, de Rosales RTM. 2020. PET Imaging of Liposomal Glucocorticoids using 89Zr-oxine: Theranostic Applications in Inflammatory Arthritis. Theranostics. 10(9):3867-3879.
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