The detection and quantitation of inflammation in the central nervous system during experimental allergic encephalomyelitis using the radiopharmaceutical 99mTc-RP128.
RP128 is a novel agent which readily chelates 99mTc to form a radiopharmaceutical which binds in vivo to the tuftsin receptor located specifically on neutrophils and monocyte-macrophages, therefore removing the need for in vitro cell labelling prior to intravenous administration. We have assessed the ability of 99mTc-RP128 to detect central nervous system (CNS) inflammation in experimental allergic encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis. The radiopharmaceutical was recorded at significantly increased levels in all EAE diseased CNS tissues, compared to normal and control samples, at 0.5, 1 and 3 h post-injection using a dual radioisotope technique to correct for non-extravasated tracer (P<0.05). Moreover, extravascular accumulation of the agent could be clearly demonstrated in inflammatory tissues with minimal loss of sensitivity when the secondary isotopic correction for blood volume was omitted. In addition, 99mTc-RP128 successfully monitored glucocorticoid suppression of inflammation (P<0.05), recording a typical dose-response to increasing steroid concentration. Clearly, 99mTc-RP128 can quantitatively detect CNS inflammation and assess responses to therapy indicating potential value as an imaging agent both clinically and as a research aid. Furthermore, the rapid in vivo labelling by 99mTc-RP128 of specific inflammatory cells combined with the ability to monitor the progress of anti-inflammatory therapeutics may recommend the agent for use in a variety of inflammatory conditions.
Paul
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Department of Pharmacology, School of Pharmacy and Pharmacology, University of Bath, Bath, UK. carolyn.paul@luton.ac.uk
Peers
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Woodhouse
L E
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Thornback
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Goodbody
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Bolton
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D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging*; D003907:Dexamethasone / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy; D005938:Glucocorticoids / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D051381:Rats; D011917:Rats, Inbred Lew
D005938:Glucocorticoids; D009842:Oligopeptides; D015609:Organotechnetium Compounds; C411942:technetium Tc 99m RP128; D003907:Dexamethasone