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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 12/2008

01.12.2008 | Original Article

Dynamic 18F-fluoride small animal PET to noninvasively assess renal function in rats

verfasst von: Uta Schnöckel, Stefan Reuter, Lars Stegger, Eberhard Schlatter, Klaus P. Schäfers, Sven Hermann, Otmar Schober, Gert Gabriëls, Michael Schäfers

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 12/2008

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Abstract

Purpose

Renal function can be quantified by both laboratory and scintigraphic methods. In the case of small animal diagnostics, scintigraphic image-based methods are ideal since they can assess split renal function, work noninvasively, and can be repeated. The aim of this study is to validate a 18F-PET-based method to quantify renal function in rats.

Materials and methods

Fluoride clearance was calculated from a dynamic whole body listmode acquisition of 60 min length in a small animal PET scanner following an i.v. injection of 15 MBq 18F-fluoride. Volumes of interest (VOIs) were placed in the left ventricle and the bladder as well as traced around the kidney contours. The respective time–activity curves (TAC) were calculated. The renal 18F-clearance was calculated by the ratio of the total renal excreted activity (bladder VOI) and the integral of the blood TAC. PET-derived renal function was validated by intraindividual measurements of creatinine clearance (n = 23), urea clearance (n = 23), and tubular excretion rate (TER-MAG3). The split renal function was derived from the injection of the clinically available radionuclide 99mTc-mercaptotriglycine by blood sampling and planar renography (n = 8).

Results

In all animals studied, PET revealed high-quality TACs. PET-derived renal fluoride clearance was linearly correlated with intraindividual laboratory measures (PET vs. creatinine: r = 0.78; PET vs. urea: r = 0.73; PET vs. TER-MAG3: r = 0.73). Split function was comparable (18F-PET vs. MAG3-renography: r = 0.98). PET-derived measures were highly reproducible.

Conclusions

18F-PET is able to noninvasively assess renal function in rats and provides a significant potential for serial studies in different experimental scenarios.
Literatur
1.
Zurück zum Zitat Rahn KH, Heidenreich S, Bruckner D. How to assess glomerular function and damage in humans. J Hypertens 1999;17:309–17.PubMedCrossRef Rahn KH, Heidenreich S, Bruckner D. How to assess glomerular function and damage in humans. J Hypertens 1999;17:309–17.PubMedCrossRef
2.
Zurück zum Zitat Levey AS. Measurement of renal function in chronic renal disease. Kidney Int 1990;38:167–84.PubMedCrossRef Levey AS. Measurement of renal function in chronic renal disease. Kidney Int 1990;38:167–84.PubMedCrossRef
3.
Zurück zum Zitat Berlyne GM, Varley H, Nilwarangkur S, Hoerni M. Endogenous creatinine clearance and glomerula filtration rate. Lancet 1964;22:874–6.CrossRef Berlyne GM, Varley H, Nilwarangkur S, Hoerni M. Endogenous creatinine clearance and glomerula filtration rate. Lancet 1964;22:874–6.CrossRef
4.
Zurück zum Zitat Brochner-Mortensen J. Current status on assessment and measurement of glomerular filtration rate. Clin Physiol 1985;5:1–17.PubMedCrossRef Brochner-Mortensen J. Current status on assessment and measurement of glomerular filtration rate. Clin Physiol 1985;5:1–17.PubMedCrossRef
5.
Zurück zum Zitat Durand E, Prigent A. The basics of renal imaging and function studies. Q J Nucl Med 2002;46:249–67.PubMed Durand E, Prigent A. The basics of renal imaging and function studies. Q J Nucl Med 2002;46:249–67.PubMed
6.
Zurück zum Zitat Boubaker A, Prior JO, Meuwly JY, Bischof-Delaloye A. Radionuclide investigations of the urinary tract in the era of multimodality imaging. J Nucl Med 2006;47:1819–36.PubMed Boubaker A, Prior JO, Meuwly JY, Bischof-Delaloye A. Radionuclide investigations of the urinary tract in the era of multimodality imaging. J Nucl Med 2006;47:1819–36.PubMed
7.
Zurück zum Zitat Lorenz JN. Considerations for the evaluation of renal function in genetically engineered mice. Curr Opin Nephrol Hypertens 2001;10:65–9.PubMedCrossRef Lorenz JN. Considerations for the evaluation of renal function in genetically engineered mice. Curr Opin Nephrol Hypertens 2001;10:65–9.PubMedCrossRef
8.
Zurück zum Zitat Spak CJ, Berg U, Ekstrand J. Renal clearance of flouride in children and adolescents. Pediatrics 1985;75(3):575–9.PubMed Spak CJ, Berg U, Ekstrand J. Renal clearance of flouride in children and adolescents. Pediatrics 1985;75(3):575–9.PubMed
9.
Zurück zum Zitat Whitford GM, Pashley DH, Stringer GI. Fluoride renal clearance: a pH-dependent event. Am J Physiol 1976;230:527–32.PubMed Whitford GM, Pashley DH, Stringer GI. Fluoride renal clearance: a pH-dependent event. Am J Physiol 1976;230:527–32.PubMed
10.
Zurück zum Zitat Whitford GM. Intake and metabolism of fluoride. Adv Dent Res 1994;8:5–14.PubMed Whitford GM. Intake and metabolism of fluoride. Adv Dent Res 1994;8:5–14.PubMed
11.
12.
Zurück zum Zitat Wieland BW, Bida GT, Padgett HC, Go H. Current status of CTI target systems for the production of PET radiochemicals. Proceedings of the 3rd Workshop on Targetry and Target Chemistry, Vancouver, British Columbia, Canada, 19–23 June 1989. Wieland BW, Bida GT, Padgett HC, Go H. Current status of CTI target systems for the production of PET radiochemicals. Proceedings of the 3rd Workshop on Targetry and Target Chemistry, Vancouver, British Columbia, Canada, 19–23 June 1989.
13.
Zurück zum Zitat Schäfers KP, Reader AJ, Kriens M, Knoess C, Schober O, Schafers M. Performance evaluation of the 32-module quadHIDAC small animal PET scanner. J Nucl Med 2005;46:996–1004.PubMed Schäfers KP, Reader AJ, Kriens M, Knoess C, Schober O, Schafers M. Performance evaluation of the 32-module quadHIDAC small animal PET scanner. J Nucl Med 2005;46:996–1004.PubMed
14.
Zurück zum Zitat Bubeck B, Piepenburg R, Grethe U, Ehrig B, Hahn K. A new principle to normalize plasma concentrations allowing single-sample clearance determinations in both children and adults. Eur J Nucl Med 1992;19:511–6.PubMedCrossRef Bubeck B, Piepenburg R, Grethe U, Ehrig B, Hahn K. A new principle to normalize plasma concentrations allowing single-sample clearance determinations in both children and adults. Eur J Nucl Med 1992;19:511–6.PubMedCrossRef
15.
Zurück zum Zitat Smuts D. B. Ein experimenteller Beitrag zur Berechnung der Körperoberfläche von Maus, Meerschweinchen und Kaninchen. Pflügers Archiv Eur J Physiol 1933;1:105–10.CrossRef Smuts D. B. Ein experimenteller Beitrag zur Berechnung der Körperoberfläche von Maus, Meerschweinchen und Kaninchen. Pflügers Archiv Eur J Physiol 1933;1:105–10.CrossRef
16.
Zurück zum Zitat Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–10.PubMed Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–10.PubMed
17.
Zurück zum Zitat Charkes ND, Brookes M, Makler PT Jr. Studies of skeletal tracer kinetics: II. Evaluation of a five-compartment model of [18F]fluoride kinetics in rats. J Nucl Med 1979;20:1150–7.PubMed Charkes ND, Brookes M, Makler PT Jr. Studies of skeletal tracer kinetics: II. Evaluation of a five-compartment model of [18F]fluoride kinetics in rats. J Nucl Med 1979;20:1150–7.PubMed
18.
Zurück zum Zitat Park-Holohan SJ, Blake GM, Fogelman I. Quantitative studies of bone using (18)F-fluoride and (99 m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics. Nucl Med Commun 2001;22:1037–44.PubMedCrossRef Park-Holohan SJ, Blake GM, Fogelman I. Quantitative studies of bone using (18)F-fluoride and (99 m)Tc-methylene diphosphonate: evaluation of renal and whole-blood kinetics. Nucl Med Commun 2001;22:1037–44.PubMedCrossRef
19.
Zurück zum Zitat Yang B, Bankir L. Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol 2005;288:881–96.CrossRef Yang B, Bankir L. Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol 2005;288:881–96.CrossRef
20.
Zurück zum Zitat Darling IM, Morris ME. Evaluation of “true” creatinine clearance in rats reveals extensive renal secretion. Pharm Res 1991;8:1318–22.PubMedCrossRef Darling IM, Morris ME. Evaluation of “true” creatinine clearance in rats reveals extensive renal secretion. Pharm Res 1991;8:1318–22.PubMedCrossRef
21.
Zurück zum Zitat Hawkins RA, Choi Y, Huang SC, Hoh CK, Dahlbom M, Schiepers C, Satyamurthy N, Barrio JR, Phelps ME. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med 1992;33:633–42.PubMed Hawkins RA, Choi Y, Huang SC, Hoh CK, Dahlbom M, Schiepers C, Satyamurthy N, Barrio JR, Phelps ME. Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med 1992;33:633–42.PubMed
22.
Zurück zum Zitat Nemzek JA, Bolgos GL, Williams BA, Remick DG. Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site. Inflamm Res 2001;50(10):523–7.PubMedCrossRef Nemzek JA, Bolgos GL, Williams BA, Remick DG. Differences in normal values for murine white blood cell counts and other hematological parameters based on sampling site. Inflamm Res 2001;50(10):523–7.PubMedCrossRef
23.
Zurück zum Zitat Jarnberg PO, Ekstrand J, Irestedt L. Renal fluoride excretion and plasma fluoride levels during and after enflurane anesthesia are dependent on urinary pH. Anesthesiology 1981;54:48–52.PubMedCrossRef Jarnberg PO, Ekstrand J, Irestedt L. Renal fluoride excretion and plasma fluoride levels during and after enflurane anesthesia are dependent on urinary pH. Anesthesiology 1981;54:48–52.PubMedCrossRef
24.
Zurück zum Zitat Rouch AJ, Whitford GM, Campbell HT. Fluoride flux in the rabbit CCD: a pH-dependent event. Kidney Int 1992;41:342–9.PubMedCrossRef Rouch AJ, Whitford GM, Campbell HT. Fluoride flux in the rabbit CCD: a pH-dependent event. Kidney Int 1992;41:342–9.PubMedCrossRef
25.
Zurück zum Zitat Yagil Y, Myers BD, Jamison RL. Course and pathogenesis of postischemic acute renal failure in the rat. Am J Physiol 1988;255:257–64. Yagil Y, Myers BD, Jamison RL. Course and pathogenesis of postischemic acute renal failure in the rat. Am J Physiol 1988;255:257–64.
26.
Zurück zum Zitat Kharasch ED, Frink EJ Jr, Artru A, Michalowski P, Rooke GA, Nogami W. Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function. Anesth Analg 2001;93:1511–20.PubMedCrossRef Kharasch ED, Frink EJ Jr, Artru A, Michalowski P, Rooke GA, Nogami W. Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function. Anesth Analg 2001;93:1511–20.PubMedCrossRef
Metadaten
Titel
Dynamic 18F-fluoride small animal PET to noninvasively assess renal function in rats
verfasst von
Uta Schnöckel
Stefan Reuter
Lars Stegger
Eberhard Schlatter
Klaus P. Schäfers
Sven Hermann
Otmar Schober
Gert Gabriëls
Michael Schäfers
Publikationsdatum
01.12.2008
Verlag
Springer-Verlag
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 12/2008
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-008-0878-y

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