{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:11:44Z","timestamp":1791299504080,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,3,9]],"date-time":"2012-03-09T00:00:00Z","timestamp":1331251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>Nanobodies are promising antigen\u2010binding moieties for molecular imaging and therapeutic purposes because of their favourable pharmacological and pharmacokinetic properties. However, the capability of monovalent nanobodies to reach targets in the CNS remains to be demonstrated.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>We have assessed the blood\u2013brain barrier permeability of Nb_An33, a nanobody against the<jats:italic>Trypanosoma brucei brucei<\/jats:italic>variant\u2010specific surface glycoprotein (VSG). This analysis was performed in healthy rats and in rats that were in the encephalitic stage of African trypanosomiasis using intracerebral microdialysis, single photon emission computed tomography (SPECT) or a combination of both methodologies. This enabled the quantification of unlabelled and<jats:sup>99m<\/jats:sup>Tc\u2010labelled nanobodies using, respectively, a sensitive VSG\u2010based nanobody\u2010detection<jats:sc>elisa<\/jats:sc>, radioactivity measurement in collected microdialysates and SPECT image analysis.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>The combined read\u2010out methodologies showed that Nb_An33 was detected in the brain of healthy rats following i.v. injection, inflammation\u2010induced damage to the blood\u2013brain barrier, as in the late encephalitic stage of trypanosomiasis, significantly increased the efficiency of passage of the nanobody through this barrier. Complementing SPECT analyses with intracerebral microdialysis improved analysis of brain disposition. There is clear value in assessing penetration of the blood\u2013brain barrier by monovalent nanobodies in models of CNS inflammation. Our data also suggest that rapid clearance from blood might hamper efficient targeting of specific nanobodies to the CNS.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>Nanobodies can enter the brain parenchyma from the systemic circulation, especially in pathological conditions where the blood\u2013brain barrier integrity is compromised.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01723.x","type":"journal-article","created":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T11:58:59Z","timestamp":1319198339000},"page":"2341-2353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Using microdialysis to analyse the passage of monovalent nanobodies through the blood\u2013brain 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