An approach to develop personalized radiopharmaceuticals by modifying 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG).

The 2-[18F]FDG was modified with two bifunctional tetrazines aminooxy-acetic acid-6-(2-aminooxy-acetoxy)-[1,2,4,5] tetrazin-3-yl ester (Tz1) and {3-[4-(6-phenyl-[1,2,4,5]tetrazin-3-yl)-phenoxy]-propyl}-hydrazine (Tz2) via oxime and hydrazone formation. The radiolabeling was carried out as one-pot reaction with following parameters: temperature 70-75°C; catalyst p- diaminobenzene (Cat.); pH = 4.2; time 30 minutes; RCY = 70-99%. The radiolabeled tetrazines are appropriate for further bioorthogonal (pretargeting) strategy by click reactions with trans-cyclooctene conjugated bioactive molecules. The methodology is applicable to standard clinical conditions.