Single-step radiosynthesis and in vivo evaluation of a novel fluorine-18 labeled hippurate for use as a PET renal agent

ObjectiveThe objective of this study was to investigate a new fluorine-18 labeled hippurate, m-cyano-p-[18 F]fluorohippurate ([18 F]CNPFH), as a potential radiopharmaceutical for evaluating renal function by PET.Methods[18 F]CNPFH was synthesized by a direct one-step nucleophilic aromatic substitution using an 18 F-for-[N(CH3)3]+-reaction. In vivo stability was determined by HPLC analysis of urine collected from a healthy rat at 30 min p.i. of [18 F]CNPFH. The plasma protein binding (PPB) and erythrocyte uptake of [18 F]CNPFH were determined using blood collected from healthy rats at 5 min p.i. Biodistribution studies were conducted in healthy rats at 10 min and 1 h p.i. of [18 F]CNPFH. Dynamic PET/CT imaging data were acquired in normal rats. For comparison, the same rats underwent an identical imaging study using the previously reported p-[18 F]fluorohippurate ([18 F]PFH) renal agent.Results[18 F]CNPFH demonstrated high in vivo stability with no metabolic degradation. The in vivo PPB and erythrocyte uptake of [18 F]CNPFH were found to be comparable to those of [18 F]PFH. Biodistribution and dynamic PET/CT imaging studies revealed a rapid clearance of [18 F]CNPFH primarily through the renal–urinary pathway. However, unlike [18 F]PFH, a minor (about 12%) fraction was eliminated via the hepatobiliary route. The PET-derived [18 F]CNPFH renograms revealed an average time-to-peak (Tmax) of 3.2 ± 0.4 min which was similar to [18 F]PFH, but the average time-to-half-maximal activity (11.4 ± 2.8 min) was found to be higher than that of [18 F]PFH (7.1 ± 1.3 min).ConclusionsOur in vivo results indicate that [18 F]CNPFH has renogram characteristics similar to those of [18 F]PFH, however, the unexpected hepatobiliary elimination is adding undesirable background signal in the PET images.