Liquid Chromatography‐Tandem Mass Spectrometry Methods for Rapid Measurement of the Molar Activity ( A m ) of Cyclotron‐Produced [ 18 F]Fluoride and Derived Radiotracers

Fluorine‐18 is an attractive positron‐emitter for positron emission tomography (PET) because of its half‐life ( t 1/2 = 109.8 min) and availability as [ 18 F]fluoride ion in high activity from biomedical cyclotrons. For 18 F‐labeled tracers intended to image low‐density protein targets (e.g., receptors, transporters and enzymes), the molar activity ( A m ) must be high (usually > 37 GBq μmol −1 ) to comply with the tracer principle, avoid attenuation of specific signal, and minimize pharmacological effects. Typically, A m is determined by measuring radioactivity with an ionization chamber and total tracer isotopologue mass with high‐performance liquid chromatography with ultraviolet absorbance detection. Molar activities often vary widely across day‐to‐day tracer productions and between PET radiochemistry laboratories. The terminal radiometric methods provide little insight into sources of carrier. Here, we describe accurate and simple nonradiometric methods for measuring A m for [ 18 F]fluoride through highly sensitive liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) on two rapidly derived surrogates, [ 18 F]fallypride and [ 18 F]4‐(pyrrolidine‐1‐carbonyl)benzenesulfonyl fluoride. These methods can serve as forensic tools for investigating the sources of carrier in tracer syntheses and for A m determinations during routine tracer productions. Moreover, the LC‐MS/MS technique can be applied to radiotracers lacking a strong UV chromophore, as with [ 18 F]2‐fluoro‐2‐deoxy‐D‐glucose tetraacetate, an intermediate in the synthesis of the most widely used PET tracer, [ 18 F]2‐fluoro‐2‐deoxy‐D‐glucose.