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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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Para-[18F]-fluorohippurate

[18F]-PFH

, PhD and , PhD.

Author Information
, PhD
The University of Oklahoma College of Pharmacy
, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD 20894

Created: ; Last Update: February 24, 2011.

Chemical name:Para-[18F]-fluorohippurateimage 103910894 in the ncbi pubchem database
Abbreviated name:[18F]-PFH
Synonym:
Agent Category:Compound
Target:Organic anion transporter 1 (OAT1)
Target Category:Transporter
Method of detection:Positron emission tomography (PET)
Source of signal / contrast:18F
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on the above structure of [18F]-PFH for additional information in PubChem.

Background

[PubMed]

Although ortho-[131I]-iodohippurate ([131I]-OIH) is considered a gold standard for renal imaging and provides quantitative results from single-photon emission tomography (SPECT), images produced with this agent are not superior to those obtained with either [99m Tc]-labeled mercaptoacetylglycylglycylglycine ([99mTc]-MAG3) or [99mTc]-labeled diethylenetriamine pentaacetic acid ([99mTc]-DTPA) (1). As a consequence, [99mTc]-MAG3 is often used in the clinic with planar gamma imaging to evaluate kidney function and perform renal scans (renography) (2). However, even with these radiolabeled compounds, a low signal/background ratio is obtained from the kidneys due to a differential attenuation of the 99mTc-gamma radiation between the two organs that results in the generation of poor quantitative data. Therefore, investigators are evaluating the use of dynamic SPECT or positron emission tomography (PET) to assess kidney function or for renography because these modalities provide substantially superior quantitative results compared to planar imaging. Between these two imaging methods, PET offers several benefits over SPECT for renography because PET has higher spatial resolution and sensitivity, shows minimal differential signal attenuation between the kidneys, and can be used for real-time acquisition of the dynamic images (3). In an effort to develop an alternate tracer that can be used to evaluate kidney function and perform renography with PET, para-18F-fluorohippurate ([18F]-PFH), a renal tubular agent, was identified as a potential candidate by Awasthi et al. (3). The investigators hypothesized that [18F]-PFH could be a superior PET renal imaging agent compared to [99mTc]-MAG3 because of its pharmacokinetic and imaging characteristics. In a preliminary investigation, the biodistribution of this radiolabeled compound was studied in normal rats and confirmed by performing a combination of PET and computed tomography (PET/CT) on the animals (3).

Other sources of Information

References for [131I]-iodohippurate in PubMed

References for [99mTc]-MAG3 in PubMed

Clinical trials with [99mTc]-MAG3

References for [99mTc]-DTPA in PubMed

Clinical trials with [99mTc]-DTPA

Synthesis

[PubMed]

[18F]-PFH was synthesized by the conjugation of N-succinimidyl-4-18F-fluorobenzoate ([18F]-SFB) with glycine and purified with high-performance liquid chromatography (HPLC) (3). The radiochemical yield and purity of [18F]-PFH were 91%–95% and >99%, respectively, as determined with radio-HPLC. The total time of synthesis and the specific activity of 18F-PFH were not reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

[18F]-PFH was reported to be stable in human plasma for at least 1 h at 37 ºC as determined with HPLC. No degradation products of the tracer were generated during this period of incubation.

Animal Studies

Rodents

[PubMed]

Using radio-HPLC, the in vivo stability of [18F]-PFH was determined from a urine sample obtained from a normal Sprague-Dawley rat at 40 min postinjection (p.i.) of the radiochemical (3). No metabolites of the tracer were detected in the urine, indicating that the labeled compound was excreted intact in vivo.

In vivo plasma protein binding and erythrocyte uptake of [18F]-PFH was studied in normal Sprague-Dawley rats (n = 2 animals) (3). At 5 min p.i., 45.3% and 16.5% of the label was determined to be bound to the plasma protein and the erythrocytes, respectively. The plasma clearance of 18F-PFH was reported to be 4.17 ± 1.13 ml/min per 100 g in normal rats (control), which was reduced by ~50% to 2.06 ± 0.05 ml/min per 100 g (P = 0.034) in rats treated with probenecid (4-[(dipropylamino)sulfonyl]benzoic acid), suggesting that renal excretion of radioactivity may occur principally by renal tubular secretion.

The biodistribution of [18F]-PFH was investigated in anesthetized normal Sprague-Dawley rats (n = 4 animals/group) (3). A rapid clearance of radioactivity from the blood was observed, and only 3.54 ± 0.14% and 0.31 ± 0.18% of the injected dose (% ID) remained in circulation at 10 min and 1 hr p.i., respectively. The activity of [18F]-PFH excreted in urine at 10 min and 1 hr after injection was 72.1 ± 6.4% ID and 88.6 ± 6.2% ID, respectively. Less than 0.5% ID of [18F]-PFH was collectively detected in the blood, heart, lungs, liver, and spleen at 1 hr p.i.

In another study, PET/CT renograms were performed on normal Sprague-Dawley rats (n = 5 animals) injected with [18F]-PFH. From these images, the average time of peak activity in the kidney was determined to be at 3.0 ± 1.0 min p.i., and the average time of half-maximal activity in these organs was at 5.6 ± 2.4 min p.i (3). The average fraction of radioactivity in the right kidney at peak maximum was determined to be 0.51 ± 0.06.

From these results, the investigators concluded that more studies are necessary before [18F]-PFH can be used as a radiopharmaceutical to assess renal function by PET imaging (3).

Other Non-Primate Mammals

[PubMed]

No references are currently available.

Non-Human Primates

[PubMed]

No references are currently available.

Human Studies

[PubMed]

No references are currently available.

Supplemental Information

[Disclaimers]

No information is currently available.

References

1.
Itoh K. 99mTc-MAG3: review of pharmacokinetics, clinical application to renal diseases and quantification of renal function. Ann Nucl Med. 2001;15(3):179–90. [PubMed: 11545186]
2.
Taylor A. Jr, Eshima D., Fritzberg A.R., Christian P.E., Kasina S. Comparison of iodine-131 OIH and technetium-99m MAG3 renal imaging in volunteers. J Nucl Med. 1986;27(6):795–803. [PubMed: 2940350]
3.
Awasthi V., Pathuri G., Agashe H.B., Gali H. Synthesis and in vivo evaluation of p-18F-Fluorohippurate as a new radiopharmaceutical for assessment of renal function by PET. J Nucl Med. 2011;52(1):147–53. [PubMed: 21149490]

This MICAD chapter is not included in the Open Access Subset, because it was authored / co-authored by one or more investigators who was not a member of the MICAD staff.

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