99mTc-MAG3 scintigraphy for the longitudinal follow-up of kidney function in a mouse model of renal ischemia-reperfusion injury

Herrler, Tanja; Wang, Hao; Tischer, A.; Bartenstein, Peter; Jauch, Karl‐Walter; Guba, Markus; Diemling, Markus; Nimmon, C.C.; Hacker, Marcus

doi:10.1186/2191-219x-2-2

Cited by 12 publications

(10 citation statements)

References 14 publications

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“…Results of the scans at week one, six and eleven are not shown. As described previously, preserved renal function is observed by a fast and steep increase of [ 99m Tc]Tc-MAG3 in the kidneys with rapid excretion as well as preserved FUR values comparable to baseline [16,17]. The renal curve in group 1 (placebo) is almost unchanged compared to baseline.…”

Section: Bun Creatinine and Blood Count During Follow-upsupporting

confidence: 61%

“…[ 99m Tc]Tc-MAG3-scintigraphy was performed as described in previously published protocols [14][15][16][17]. Inhalational anaesthesia with 2.0% of isoflurane in pure oxygen was induced and maintained with a concentration of 1.5%.…”

Section: Renal Scintigraphymentioning

confidence: 99%

“…Furthermore, the fractional uptake rate (FUR) was calculated to assess renal clearance from the renograms [16]. FUR is defined as the fractional uptake of a tracer in the blood by an organ per time unit and can be calculated in the following way: FUR = P(0) × (k l +k r )/[IA].…”

Section: Renal Scintigraphymentioning

confidence: 99%

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Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats

Zellmer¹,

Yen

Kaiser³

et al. 2020

EJNMMI Res

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Purpose: Peptide receptor radionuclide therapy (PRRT) with [ 177 Lu]Lu-DOTA 0 ,TYR 3 -octreotate ([ 177 Lu]Lu-DOTA-TATE) and the mechanistic target of rapamycin (mTOR) inhibitor everolimus are both approved for the treatment of neuroendocrine tumours (NET). However, tumour progression is still frequent, and treatment strategies need further improvement. One possible approach could be to combine different therapy options. In this study, we investigated the toxicity of a combined treatment with everolimus and [ 177 Lu]Lu-DOTA-TATE in female Lewis rats. Methods: Animals received 200 MBq of [ 177 Lu]Lu-DOTA-TATE once and/or 5 mg/kg body weight everolimus or placebo weekly for 16 weeks and were divided into four groups (group 1, placebo; group 2, everolimus; group 3, placebo + [ 177 Lu]Lu-DOTA-TATE; group 4, everolimus + [ 177 Lu]Lu-DOTA-TATE). Blood levels of creatinine and blood urea nitrogen (BUN) were assessed weekly to monitor nephrotoxicity, and a full blood count was performed at the time of euthanasia to monitor myelotoxicity. Additionally, renal function was analysed by sequential [ 99m Tc]Tcmercaptoacetyltriglycine ([ 99m Tc]Tc-MAG3) scintigraphies. Histopathological examination was performed in all the kidneys using a standardized renal damage score (RDS). Results: Rats receiving everolimus showed a significantly lower increase in creatinine levels than those receiving placebo. Everolimus therapy reduced white blood count significantly, which was not observed for [ 177 Lu]Lu-DOTA-TATE. Functional renal scintigraphies using [ 99m Tc]Tc-MAG3 showed a compromised initial tracer uptake after PRRT and slower but still preserved excretion after everolimus. Histology showed no significant RDS differences between groups. Conclusion: Renal scintigraphy is a highly sensitive tool for the detection of renal function impairment after a combination of everolimus and PRRT. Additional treatment with everolimus does not increase renal and haematological toxicity of PRRT with [ 177 Lu]Lu-DOTA-TATE.

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Section: Bun Creatinine and Blood Count During Follow-upsupporting

confidence: 61%

Section: Renal Scintigraphymentioning

confidence: 99%

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Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats

Zellmer¹,

Yen

Kaiser³

et al. 2020

EJNMMI Res

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“…MR-Imaging studies investigating acute kidney injury observed indirect changes such as alteration of the cortical and medullary T2-relaxation-time or reduced perfusion [36] – [39] . A MR-technique quantifying tissue anisotropy as an indirect measure of tubular integrity is Tensor Imaging, commonly based on diffusion (DTI) [7] , [40] – [42] or as described recently on susceptibility (STI) [43] .…”

Section: Discussionmentioning

confidence: 99%

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Velroyen¹,

Bech

Zanette³

et al. 2014

PLoS ONE

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PurposeThe aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.Material and MethodsThe effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.ResultsGB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.ConclusionIn conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.

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“…Glomerular filtration rate (GFR) is considered the best indicator of overall kidney function for early monitoring and optimization of therapeutic interventions (1,2). However, the accurate quantification of GFR, which is of particular importance in the setting of clinical research, still remains challenging (3,4).…”

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confidence: 99%

Initial Preclinical Evaluation of ¹⁸F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent

et al. 2016

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Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18 F-fluorodeoxysorbitol ( 18 F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available 18 F-FDG. We tested the feasibility of 18 F-FDS renal PET imaging in rats. Methods: The systemic and renal distribution of 18 F-FDS were determined by dynamic 35-min PET imaging (15 frames · 8 s, 26 frames · 30 s, 20 frames · 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected 99m Tc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of 18 F-FDS were determined. Results: In vivo PET imaging visualized rapid excretion of the administrated 18 F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [T max ] right [R] 5 2.8 ± 1.2 min, T max left [L] 5 2.9 ± 1.5 min, the time of half maximal concentration [T 1/2max ] R 5 8.8 ± 3.7 min, T 1/2max L 5 11.1 ± 4.9 min). Postmortem tissue counting of 18 F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to 99m Tc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of 18 F-FDS was low (,0.1%), and metabolic transformation was not detected in serum and urine. Conclusion: In rat experiments, 18 F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability. The kidneys are responsible for various important functions within the body including waste excretion, fluid regulation, acidbase homeostasis, and hormone secretion. Glomerular filtration rate (GFR) is considered the best indicator of overall kidney function for early monitoring and optimization of therapeutic interventions (1,2). However, the accurate quantification of GFR, which is of particular importance in the setting of clinical research, still remains challenging (3,4). Measurement of exogenous inulin or radiolabeled markers such as 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) urinary clearance is considered the gold standard, but the applic...

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99mTc-MAG3 scintigraphy for the longitudinal follow-up of kidney function in a mouse model of renal ischemia-reperfusion injury

Cited by 12 publications

References 14 publications

Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats

Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Initial Preclinical Evaluation of ¹⁸F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent

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99mTc-MAG3 scintigraphy for the longitudinal follow-up of kidney function in a mouse model of renal ischemia-reperfusion injury

Cited by 12 publications

References 14 publications

Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats

Toxicity of a combined therapy using the mTOR-inhibitor everolimus and PRRT with [177Lu]Lu-DOTA-TATE in Lewis rats

X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage

Initial Preclinical Evaluation of 18F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent

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Initial Preclinical Evaluation of ¹⁸F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent