Single-step radiosynthesis and in vivo evaluation of a novel fluorine-18 labeled hippurate for use as a PET renal agent.
OBJECTIVE
The 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(CH(3))(3)](+)-reaction. In vivo stability was determined by HPLC analysis of urine collected from a healthy rat at 30min 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 5min p.i. Biodistribution studies were conducted in healthy rats at 10min and 1h 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 (T(max)) of 3.2±0.4min which was similar to [(18)F]PFH, but the average time-to-half-maximal activity (11.4±2.8min) was found to be higher than that of [(18)F]PFH (7.1±1.3min).


CONCLUSIONS
Our 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.
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Gopal
G
Pathuri
Andria F
AF
Hedrick
Vibhudutta
V
Awasthi
Hariprasad
H
Gali
D000818:Animals; D060326:Chemistry Techniques, Synthetic; D004355:Drug Stability; D005260:Female; D005462:Fluorine Radioisotopes; D006626:Hippurates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging* / Q000502:physiology; D049268:Positron-Emission Tomography / Q000379:methods*; D011854:Radiochemistry; D011866:Radioisotope Renography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D005462:Fluorine Radioisotopes; D006626:Hippurates; D019275:Radiopharmaceuticals; C030514:hippuric acid