The traditional approachused to deliver medical isotopes to specific biomarkers involves linking radioisotopes to a targeting construct like an antibody. After administering the radiolabelled drug, and following a delay to allow for accumulation at the site of interest and clearance from non-target tissues, images are acquired. More recently, groups have shown exciting results using pretargeting where a targeting vector is administered and allowed to accumulate and clear prior to injection of a radiolabeled small molecule that selectively reacts with the vector. The coupling between the two components is made possible through bioorthogonal chemistry. One example of bioorthogonal chemistry is the reaction transcyclooctene (TCO)-functionalized biomolecules and radiolabeled tetrazines (Tz). The TCO-Tz reaction is highly selective and rapid and has generated exquisite images of tumors in preclinical models.
In the Valliant Research Group, we are developing new radiolabelled tetrazines including 18F and 99mTc labelled tetrazines. This work involves the development of novel chelates, metal complexes and radiochemistry and the evaluation of new agents in cells and animal models.
The above movie shows the traditional approach to targeting medical isotopes (M) and the more recent strategy involving pre-targeting and bioorthogonal chemistry.