Extended reports
Technetium-99m labelled liposomes to image experimental arthritis
a Departments of Nuclear Medicine , b and
Internal Medicine , c University Hospital Nijmegen, the Netherlands
Department of Pharmaceutics, Utrecht
Institute for Pharmaceutical Sciences, University Utrecht, the
Netherlands , d Departamento de Biotecnologia, IBQTA-INETI,
Portugal
Correspondence to: Dr O C Boerman, Department of Nuclear Medicine, University Hospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, the Netherlands.
Accepted for publication 24 February 1997
OBJECTIVES
Liposomes sterically stabilised with
polyethylene glycol (PEG) labelled with technetium-99m were tested for
their ability to image adjuvant arthritis in a rat model.
METHODSAdjuvant arthritis was induced in the
ankle joint of the left hind foot by injection of Mycobacterium
butyricum in Freund's incomplete adjuvant in the foot pad.
Seven days later animals received the following radiopharmaceuticals
labelled with 99mTc (a) non-PEG-liposomes, (b)
PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the
radiopharmaceuticals the in vivo distribution of the radiolabel was
monitored both scintigraphically as well as by counting the dissected
tissues at two, eight, and 24 hours after injection.
RESULTSThe pharmacokinetics of the
radiopharmaceuticals differed considerably (half life in the blood:
PEG-liposomes (18 hours) > 99mTc-IgG (3 hours) > non-PEG
liposomes (1 hour)). The inflamed focus was visualised with each of the
agents. The uptake of each of the radiopharmaceuticals in the
inflamed ankle region correlated with their residence time in the blood
(inflamed joint uptake: PEG liposomes (1.15% injected dose
(ID)/g)>99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05%
ID/g)). Quantitative analysis of the images showed that the inflamed
ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did
not exceed 4.
CONCLUSIONThis study shows that
99mTc-labelled PEG-liposomes may be an excellent agent to
visualise arthritis. Increased label uptake in the inflamed joint and
increased target to background ratios can be obtained with
PEG-liposomes because of their long circulating properties. In addition
to their use as vehicles for scintigraphic imaging of arthritis
PEG-liposomes might also be used for the site specific delivery of
antirheumatic drugs.
© 1997 by Annals of the Rheumatic Diseases
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