Novel synthesis of [18F]-fluorobenzene and pyridinecarbohydrazide-folates as potential PET radiopharmaceuticals

In an attempt to visualize folate receptors that over-express on many cancers, [F-18]fluorobenzene and pyridine carbohydrazide-folates were synthesized using two different synthetic approaches starting from nucleophilic displacement reactions on ethyl-trimethylammonium-benzoate and pyridine carboxylate precursors. The intermediates ethyl [F-18]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [F-18]-fluorobenzene and pyridine carbohydrazides followed by Coupling with NHS-folate 11 in the first approach. Whereas hydrazide-folate 5 was reacted with 2,5-dioxoazolidinyl [F-18]-fluorobenzenecarboxylate in the second approach. Based on starting [F-18]-fluoride, radiochemical yields and synthesis times were found to be around 80% (45 min) and 35% (80 min) for the first and the second approaches, respectively. The first synthetic approach holds considerable promise as a rapid and simple method for the radiofluorination of folic acid with high radiochemical yield and short time. Copyright (c) 2005 John Wiley & Sons, Ltd.