UNLABELLED: The molecular structure of p-18F-fluorohippurate (18F-PFH) is similar to that of p-aminohippurate, a gold standard for the measurement of effective renal plasma flow. The objective of this study was to investigate 18F-PFH as a new PET renal agent. METHODS: 18F-PFH was synthesized by reacting N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) with glycine at 90°C (pH 8) for 20 min. In vitro stability was determined by incubating 18F-PFH in fresh human plasma at 37°C for 60 min. In vivo stability was determined by high-performance liquid chromatography analysis of urine collected from a normal rat at 40 min after injection of 18F-PFH. The plasma protein binding and erythrocyte uptake were determined using plasma collected from a normal rat at 5 min after injection of 18F-PFH. The plasma clearance of 18F-PFH was determined using a single-injection clearance method in normal and probenecid-treated rats. Biodistribution studies were conducted in normal rats at 10 min and 1 h after injection of 18F-PFH. Dynamic PET/CT studies were conducted in normal rats injected with 18F-PFH. RESULTS: In normal rats, the plasma clearance of 18F-PFH was 4.11±1.09 mL/min/100 g, which reduced by approximately 50% (P=0.03) to 2.01±0.08 mL/min/100 g in probenecid-treated rats. About 45.3% of 18F-PFH was found to associate with plasma proteins in vivo in normal rats. Biodistribution studies of 18F-PFH in normal rats showed 72.1±6.4 percentage injected dose and 88.6±6.2 percentage injected dose, respectively, in urine at 10 min and 1 h after injection. The uptake in other organs was negligible. High-performance liquid chromatography analysis of urine collected from a rat at 40 min after injection of 18F-PFH indicated that it was excreted intact, with no metabolic products. Dynamic PET revealed a rapid clearance of 18F-PFH through the renal-urinary pathway. The PET-derived renograms revealed a time to peak activity of 3.0±1.0 min. CONCLUSION: These combined results warrant further investigation of 18F-PFH as a radiopharmaceutical for the assessment of renal function by PET.
UNLABELLED: The molecular structure of p-18F-fluorohippurate (18F-PFH) is similar to that of p-aminohippurate, a gold standard for the measurement of effective renal plasma flow. The objective of this study was to investigate 18F-PFH as a new PET renal agent. METHODS:18F-PFH was synthesized by reacting N-succinimidyl-4-18F-fluorobenzoate (18F-SFB) with glycine at 90°C (pH 8) for 20 min. In vitro stability was determined by incubating 18F-PFH in fresh human plasma at 37°C for 60 min. In vivo stability was determined by high-performance liquid chromatography analysis of urine collected from a normal rat at 40 min after injection of 18F-PFH. The plasma protein binding and erythrocyte uptake were determined using plasma collected from a normal rat at 5 min after injection of 18F-PFH. The plasma clearance of 18F-PFH was determined using a single-injection clearance method in normal and probenecid-treated rats. Biodistribution studies were conducted in normal rats at 10 min and 1 h after injection of 18F-PFH. Dynamic PET/CT studies were conducted in normal rats injected with 18F-PFH. RESULTS: In normal rats, the plasma clearance of 18F-PFH was 4.11±1.09 mL/min/100 g, which reduced by approximately 50% (P=0.03) to 2.01±0.08 mL/min/100 g in probenecid-treated rats. About 45.3% of 18F-PFH was found to associate with plasma proteins in vivo in normal rats. Biodistribution studies of 18F-PFH in normal rats showed 72.1±6.4 percentage injected dose and 88.6±6.2 percentage injected dose, respectively, in urine at 10 min and 1 h after injection. The uptake in other organs was negligible. High-performance liquid chromatography analysis of urine collected from a rat at 40 min after injection of 18F-PFH indicated that it was excreted intact, with no metabolic products. Dynamic PET revealed a rapid clearance of 18F-PFH through the renal-urinary pathway. The PET-derived renograms revealed a time to peak activity of 3.0±1.0 min. CONCLUSION: These combined results warrant further investigation of 18F-PFH as a radiopharmaceutical for the assessment of renal function by PET.
Authors: Malgorzata Lipowska; Nashwa Jarkas; Ronald J Voll; Jonathon A Nye; Jeffrey Klenc; Mark M Goodman; Andrew T Taylor Journal: Nucl Med Biol Date: 2017-12-27 Impact factor: 2.408
Authors: Chuong Nguyen; Joseph Havlicek; Quyen Duong; Sara Vesely; Ronald Gress; Liza Lindenberg; Peter Choyke; Jennifer Holter Chakrabarty; Kirsten Williams Journal: Proc Int Conf Image Proc Date: 2016-08-19
Authors: Malgorzata Lipowska; Jeffrey Klenc; Dinesh Shetty; Jonathon A Nye; Hyunsuk Shim; Andrew T Taylor Journal: Nucl Med Biol Date: 2013-12-26 Impact factor: 2.408
Authors: Rudolf A Werner; Xinyu Chen; Constantin Lapa; Kazuhiro Koshino; Steven P Rowe; Martin G Pomper; Mehrbod S Javadi; Takahiro Higuchi Journal: Eur J Nucl Med Mol Imaging Date: 2019-05-30 Impact factor: 9.236
Authors: Bruno Stieger; Jashvant D Unadkat; Bhagwat Prasad; Oliver Langer; Hariprasad Gali Journal: Drug Metab Dispos Date: 2014-09-23 Impact factor: 3.922