Abstract
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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 (Tmax) 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