Imperial College London
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PROFESSOR NICHOLAS LONG

Faculty of Natural Sciences, Department of Chemistry

Sir Edward Frankland BP Chair -Inorganic Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5781n.long Website CV

 
 
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Location

 

501jMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gawne:2020:10.7150/thno.40403,
author = {Gawne, PJ and Clarke, F and Turjeman, K and Cope, AP and Long, NJ and Barenholz, Y and Terry, SYA and de, Rosales RTM},
doi = {10.7150/thno.40403},
journal = {Theranostics},
pages = {3867--3879},
title = {PET imaging of liposomal glucocorticoids using Zr-89-oxine: theranostic applications in inflammatory arthritis},
url = {http://dx.doi.org/10.7150/thno.40403},
volume = {10},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 potentia
AU  - Gawne,PJ
AU  - Clarke,F
AU  - Turjeman,K
AU  - Cope,AP
AU  - Long,NJ
AU  - Barenholz,Y
AU  - Terry,SYA
AU  - de,Rosales RTM
DO  - 10.7150/thno.40403
EP  - 3879
PY  - 2020///
SN  - 1838-7640
SP  - 3867
TI  - PET imaging of liposomal glucocorticoids using Zr-89-oxine: theranostic applications in inflammatory arthritis
T2  - Theranostics
UR  - http://dx.doi.org/10.7150/thno.40403
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000518773300002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/77993
VL  - 10
ER  -
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