{"id":21,"date":"2019-03-13T14:07:41","date_gmt":"2019-03-13T14:07:41","guid":{"rendered":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/?page_id=21"},"modified":"2019-09-25T15:47:10","modified_gmt":"2019-09-25T15:47:10","slug":"pretargeting","status":"publish","type":"page","link":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/pretargeting\/","title":{"rendered":"Pretargeted imaging and therapy"},"content":{"rendered":"<p><strong><u>Development of new pretargeting strategies<br \/>\n<\/u><\/strong><\/p>\n<p>Antibodies labelled with radioisotopes are frequently used to detect and characterise tumours <em>in vivo<\/em> in a non-invasive manner by PET imaging. However, antibodies suffer from prolonged residence times within the circulation and consequently high tumour-to-blood contrast ratios are only observed 5-7 days after their administration. Furthermore, the patient is also exposed to an increasing radiation dose over this timeframe. To address these problems, an imaging strategy known as \u2018pretargeting\u2019 has been developed.<\/p>\n<p>Pretargeting involves the sequential administration of (<em>i<\/em>) an antibody \u2018primary agent\u2019 and (<em>ii<\/em>) a low molecular weight radiolabelled \u2018secondary agent\u2019 which is capable of binding to the primary agent at the tumour surface. In practical terms, the antibody \u2013 which has inherently <em>slow<\/em> pharmacokinetics &#8211; is first permitted sufficient time to reach an optimal tumour-to-blood ratio (days). At this point, the radioactive secondary agent \u2013 which has <em>fast<\/em> pharmacokinetics &#8211; is administered and undergoes a rapid and selective &#8216;click&#8217; reaction with the antibody at the tumour site (minutes). This results in an improvement of imaging contrast at earlier time points after administration of the radioactive agent and leads to a significantly reduced radiation dose to the patient.<\/p>\n<p>During my previous appointment at Oxford University with Prof. Bart Cornelissen, we succeeded in developing a novel enzymatic pretargeting strategy which has demonstrated striking efficacy in models of colorectal cancer. Now, the JCK group is advancing this technology in a new direction, using bioorthogonal chemical reactions which take place inside a cancer patient to activate cancer-killing warheads localised at the tumour surface.<\/p>\n<p>You can read more about this in our recent papers on this topic, <a href=\"https:\/\/pubs.acs.org\/doi\/abs\/10.1021\/acs.molpharmaceut.7b00172\">here<\/a>, <a href=\"https:\/\/pubs.rsc.org\/en\/Content\/ArticleLanding\/2015\/CC\/C4CC10265G#!divAbstract\">here<\/a>, and <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3992206\/\">here<\/a>!<\/p>\n<p style=\"text-align: center\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-22\" src=\"http:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Pretargeting.png\" alt=\"\" width=\"1270\" height=\"485\" srcset=\"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Pretargeting.png 1270w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Pretargeting-300x115.png 300w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Pretargeting-768x293.png 768w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Pretargeting-1024x391.png 1024w, https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/files\/2019\/03\/Pretargeting-500x191.png 500w\" sizes=\"auto, (max-width: 1270px) 100vw, 1270px\" \/><strong>Pretargeted imaging is a 2-step strategy which results in high quality images soon after administration of the radiotracer and reduces the radiation dose to the patient<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Development of new pretargeting strategies Antibodies labelled with radioisotopes are frequently used to detect and characterise tumours in vivo in a non-invasive manner by PET imaging. However, antibodies suffer from prolonged residence times within the circulation and consequently high tumour-to-blood contrast ratios are only observed 5-7 days after their administration. Furthermore, the patient is also <a href='https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/pretargeting\/' class='excerpt-more'>[&#8230;]<\/a><\/p>\n","protected":false},"author":3949,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-21","page","type-page","status-publish","hentry","post-seq-1","post-parity-odd","meta-position-corners","fix"],"_links":{"self":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages\/21","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/users\/3949"}],"replies":[{"embeddable":true,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/comments?post=21"}],"version-history":[{"count":10,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages\/21\/revisions"}],"predecessor-version":[{"id":145,"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/pages\/21\/revisions\/145"}],"wp:attachment":[{"href":"https:\/\/www.staff.ncl.ac.uk\/jamesknight2\/wp-json\/wp\/v2\/media?parent=21"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}