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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 3/2018

01-06-2018 | Research Article

Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA with PET Imaging

Authors: Daniel Gündel, Ulrike Pohle, Erik Prell, Andreas Odparlik, Oliver Thews

Published in: Molecular Imaging and Biology | Issue 3/2018

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Abstract

Purpose

Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals.

Procedures

Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals.

Results

Both tracers did not bind to blood cells. [68Ga]DPTA but not [68Ga]EDTA showed strong binding to plasma proteins. For this reason, [68Ga]DPTA stayed much longer in the blood and only 30 % of the injected dose was eliminated by the kidney within 60 min whereas the excretion of [68Ga]EDTA was 89 ± 1 %. The calculated GFR using [68Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [68Ga]-DPTA, the measurements led to values which were 80 % below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR.

Conclusions

[68Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [68Ga]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.
Literature
1.
Beierwaltes WH, Harrison-Bernard LM, Sullivan JC, Mattson DL (2013) Assessment of renal function; clearance, the renal microcirculation, renal blood flow, and metabolic balance. Compr Physiol 3:165–200PubMed
2.
Schock-Kusch D, Geraci S, Ermeling E et al (2013) Reliability of transcutaneous measurement of renal function in various strains of conscious mice. PLoS One 8:e71519CrossRefPubMedPubMedCentral
3.
Von Hendy-Willson VE, Pressler BM (2011) An overview of glomerular filtration rate testing in dogs and cats. Vet J 188:156–165CrossRef
4.
Qi Z, Whitt I, Mehta A et al (2004) Serial determination of glomerular filtration rate in conscious mice using FITC-inulin clearance. Am J Physiol Renal Physiol 286:F590–F596CrossRefPubMed
5.
Henriksen UL, Henriksen JH (2015) The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention. Clin Physiol Funct Imaging 35:7–16CrossRefPubMed
6.
Santos J, Martins LS (2015) Estimating glomerular filtration rate in kidney transplantation: still searching for the best marker. World J Nephrol 4:345–353CrossRefPubMedPubMedCentral
7.
Haufe SE, Riedmuller K, Haberkorn U (2006) Nuclear medicine procedures for the diagnosis of acute and chronic renal failure. Nephron Clin Pract 103:c77–c84CrossRefPubMed
8.
Debruyn K, Vandermeulen E, Saunders JH et al (2013) Effect of background region of interest and time-interval selection on glomerular filtration ratio estimation by percentage dose uptake of 99mTc-DTPA in comparison with 51Cr-EDTA clearance in healthy cats. J Feline Med Surg 15:698–705CrossRefPubMed
9.
Hecht S, Lawson SM, Lane IF et al (2010) 99mTc-DTPA diuretic renal scintigraphy in dogs with nephroureterolithiasis. Can Vet J 51:1360–1366PubMedPubMedCentral
10.
Schnöckel U, Reuter S, Stegger L et al (2008) Dynamic 18F-fluoride small animal PET to noninvasively assess renal function in rats. Eur J Nucl Med Mol Imaging 35:2267–2274CrossRefPubMed
11.
Wakabayashi H, Werner RA, Hayakawa N et al (2016) Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent. J Nucl Med 57:1625–1628CrossRefPubMed
12.
Goethals P, Volkaert A, Vandewielle C et al (2000) 55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study. Nucl Med Biol 27:77–81CrossRefPubMed
13.
14.
Kaewput C, Vinjamuri S (2016) Comparison of renal uptake of 68Ga-DOTANOC PET/CT and estimated glomerular filtration rate before and after peptide receptor radionuclide therapy in patients with metastatic neuroendocrine tumours. Nucl Med Commun 37:1325–1332CrossRefPubMed
15.
Lee JY, Jeong JM, Kim YJ et al (2014) Preparation of Ga-68-NOTA as a renal PET agent and feasibility tests in mice. Nucl Med Biol 41:210–215CrossRefPubMed
16.
Mueller D, Breeman WA, Klette I et al (2016) Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method. Nat Protoc 11:1057–1066CrossRefPubMedPubMedCentral
17.
Basken NE, Mathias CJ, Lipka AE, Green MA (2008) Species dependence of [64Cu]Cu-Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins. Nucl Med Biol 35:281–286CrossRefPubMedPubMedCentral
18.
Daniel GB, Mitchell SK, Mawby D et al (1999) Renal nuclear medicine: a review. Vet Radiol Ultrasound 40:572–587CrossRefPubMed
19.
Fleming JS, Zivanovic MA, Blake GM, Burniston M, Cosgriff PS, British Nuclear Medicine S (2004) Guidelines for the measurement of glomerular filtration rate using plasma sampling. Nucl Med Commun 25:759–769CrossRefPubMed
20.
Wanasundara SN, Wesolowski MJ, Barnfield MC et al (2016) Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h. Nucl Med Commun 37:79–86PubMed
21.
Jobin J, Bonjour JP (1985) Measurement of glomerular filtration rate in conscious unrestrained rats with inulin infused by implanted osmotic pumps. Am J Phys 248:F734–F738
22.
Rehling M, Nielsen LE, Marqversen J (2001) Protein binding of 99Tcm-DTPA compared with other GFR tracers. Nucl Med Commun 22:617–623CrossRefPubMed
23.
Russell CD, Bischoff PG, Rowell KL et al (1988) Estimation of extracellular fluid volume from plasma clearance on technetium-99m DTPA by a single-injection, two-sample method. J Nucl Med 29:255–258PubMed
24.
Hofman M, Binns D, Johnston V et al (2015) 68Ga-EDTA PET/CT imaging and plasma clearance for glomerular filtration rate quantification: comparison to conventional 51Cr-EDTA. J Nucl Med 56:405–409CrossRefPubMed
25.
26.
Brøchner-Mortensen J (1985) Current status on assessment and measurement of glomerular filtration rate. Clin Physiol 5:1–17CrossRefPubMed
Metadata
Title
Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA with PET Imaging
Authors
Daniel Gündel
Ulrike Pohle
Erik Prell
Andreas Odparlik
Oliver Thews
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 3/2018
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-017-1135-1

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