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

Objectives The objective of this study was to investigate a new fluorine-18 labeled hippurate, m-cyano-p-¹⁸F-fluorohippurate (¹⁸F-CNPFH), as a potential radiopharmaceutical for evaluating renal function by PET.

Methods ¹⁸F-CNPFH was synthesized by a direct one-step nucleophilic aromatic substitution of ¹⁸F-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 ¹⁸F-CNPFH. The plasma protein binding (PPB) and erythrocyte uptake of ¹⁸F-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 hr p.i. of ¹⁸F-CNPFH. Dynamic PET/CT imaging data was acquired in normal rats. For comparison, the same rats underwent identical imaging study using previously reported p-¹⁸F-fluorohippurate (¹⁸F-PFH) renal agent.

Results ¹⁸F-CNPFH demonstrated high in vivo stability with no metabolic degradation. The in vivo PPB and erythrocyte uptake of ¹⁸F-CNPFH was found to be comparable to ¹⁸F-PFH. Biodistribution and dynamic PET/CT imaging studies revealed a rapid clearance of ¹⁸F-CNPFH primarily through renal-urinary pathway. However, unlike ¹⁸F-PFH, a minor (about 12%) fraction eliminated via hepatobiliary route. The PET-derived ¹⁸F-CNPFH renograms revealed an average time-to-peak (T_max) of 3.2 ± 0.4 min which was similar to ¹⁸F-PFH, but the average time-to-half-maximal activity (11.4 ± 2.8 min) was found to be higher than ¹⁸F-PFH (7.1 ± 1.3 min).

Conclusions Our in vivo results indicate that ¹⁸F-CNPFH has renogram characteristics similar to that of ¹⁸F-PFH, however, the unexpected hepatobiliary elimination is adding undesirable background signal in the PET images.

Research Support This work was funded by the University of Oklahoma College of Pharmacy Startup Grant