A problem in antibody-based imaging and therapy is that the antibodies stay in circulation for a long time, which leads to poor target-to-blood ratios. To address this, Tagworks has developed clearing agents that rapidly bind and remove freely circulating tagged antibodies from blood. The binding is based on the click reaction that also underlies Tagworks’ Radioimmunoimaging and -therapy and Antibody-Drug Conjugate technologies.
Clearing of antibodies can be initiated at any desired time after administration. The tetrazine-functionalized clearing agent is injected and reacts with trans-cyclooctene-tagged antibody in blood. The resulting reaction products are then rapidly taken up by the liver and spleen, allowing up to 100-fold increases in target-to-blood ratio. When incorporated in a Tagworks’ pretargeted radioimmunoimaging/therapy procedure, this approach ensures that the radiolabeled tetrazine probe is not captured by any residual antibody-tag in blood. Likewise, in a Tagworks’ Antibody-Drug Conjugate procedure, drug release in circulation is prevented. In addition, the target-to-blood ratios of directly radiolabeled antibodies can be improved by incorporating a tag on the antibody, enabling temporally controlled clearance of the tagged and radiolabeled antibody from circulation by administration of a clearing agent prior to an imaging procedure.