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

A challenge for modern medicine is the development of clinical protocols for precise diagnosis and therapy. This study aimed to propose a simple method for modification of 2-[18F]FDG used routinely in hospitals in a way, appropriate for patients' personalized radiopharmaceuticals approach.

For the purposes of the presented study chemo selective method for indirect radiofluorination was applauded to custom synthesized aminooxy- and hydrazine-functionalized tetrazines for 18F-glycolation via oxime or hydrazone formation. 2-[18F]FDG produced with medical baby cyclotron in Nuclear Medicine Clinic at the University Hospital St. Marina-Varna, was used. Thin layer chromatography (TLC) and radio TLC were used to follow the progress of synthesis and to determine radio chemical yield (RCY).

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.