Practical syntheses of DOTAGA-DBCO and DFO-DBCO, strained alkyne pre-cursors to radioimmunoconjugates for targeted alpha therapy

We describe practical methods to prepare DOTAGA-DBCO and DFO-DBCO from commercially available starting materials. DOTAGA-DBCO is available in five steps from cyclen with a 33 % overall yield at gram scale. Our synthesis of DFO-DBCO also proceeds in five steps from commercially available starting materials. These bifunctional molecules possess chelating functionality for the binding of medically important radiometals and a strained alkyne suitable for Huisgen cyclization with an azide. These syntheses represent an important step toward improved radioimmunoconjugates for imaging and therapeutic applications.