SYNTHESIS OF FLUORINATED RADIOPHARMACEUTICALS VIA ELECTROCHEMICAL FLUORINATION

摘要

Provided herein are methods and compositions for the electrochemical selective radiofluorination of aromatic molecules. The resulting fluorine-18 labeled compounds are ideal radionuclides for use in Positron Emission Tomography (PET); they are also difficult to radiolabel efficiently and with high specific activity using existing approaches. For example, radiopharmaceuticals such as [F18]L-DOPA, which is indispensable in PET brain disease imaging, may be made electrochemically with high radiochemical yield and high specific activity using 18F-. The invention process described herein opens new possibilities and provides wider access to PET tracers such as 18F-L-Dopa, since 18F- is much more widely available than the 18F2, currently used for synthesis of electron rich substrates.

主权项

1. A mixture comprising a solvent, an electrolyte, a [18F] fluoride source, and a compound of the formula: wherein,
z is an integer from 0 to 10;L1 is independently —O—, —NH—, —S—, —C(O)NH—, —NHC(O)—, —NHNH—, —S(O)—, —S(O)2—, —ONH—, or —NHO—;R1 is independently hydrogen, halogen, —N3, —CF3, —CCl3, —CBr3, —CI3, —CN, —C(O)R3A, —OR3A, —NR3AR3B, —C(O)OR3, —CONR3AR3B, —NR3AR3BC(O)R3C, —NO2, —SR3A, —SO2, —SO2Cl, —SO3R3A, —SO2NR3AR3B, —NHNR3AR3B, —ONR3AR3B, —NHC(O)NHR3AR3B, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; andR3A, R3B and R3C are independently hydrogen, halogen, —N3, —CF3, —CCl3, —CBr3, —CI3, —CN, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;wherein two R1 subsitutents are optionally joined to from a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.