A theoretical four-compartment model to evaluate separate kidney technetium-99m-MAG3 kinetics in humans

Curti, G; DeMartini, Daniele; Santaniello, B; Taddei, G.; Fresco, G

doi:10.1046/j.1523-1755.1998.00198.x

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…Most of the examples of PK models for TRT agents in the literature are for radiolabeled mAbs. [19][20][21][22][23] For example, Odom-Maryon et al successfully used a three-compartment model to represent the concentration of radiolabeled chimeric anti-CEA antibody within the blood and urine 19 in hopes of avoiding bladder and kidney radiation toxicity. Despite successfully predicting radiation dose to the kidneys and bladder, the model was unable to predict tumor radiation dose.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric Effectiveness of Targeted Radionuclide Therapy Based on a Pharmacokinetic Landscape

Grudzinski

Burnette

Weichert

et al. 2010

Cancer Biotherapy and Radiopharmaceuticals

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Assessment of targeted radionuclide therapy (TRT) agent effectiveness based on its pharmacokinetic (PK) properties could provide means to expedited agent development or its rejection. A broad PK model that predicts the relative effectiveness of TRT agents based on the relationship between their normal body (k(12), k(21)) and tumor (k(34), k(43)) PK parameters has been developed. A classic two-compartment open model decoupled from a tumor was used to represent the body. Analytically solved differential equations were used to develop a relationship that predicts TRT effectiveness. Various PK scenarios were created by pairing normal body PK parameters of 38 pharmaceuticals found in the literature with estimated tumor PK parameters. Each PK scenario resulted in a maximum permissible injected activity that limited the whole-body dose to 2 Gy and yielded a maximum delivered tumor dose. The model suggests that a k(34):k(43) ratio greater than 5 and a k(12):k(21) ratio less than 1 is effective at delivering doses that ensure sufficient solid tumor control. It was also shown that there is no direct relationship between tumor dose and acid dissociation constant (pK(a)), lipophilicity (log P), and fraction unbound (fu), which are important physicochemical properties. This study suggests that although effective TRT may be difficult to achieve for solid tumors, good TRT agents must have extremely desirable normal body PKs in conjunction with very high tumor retention. The developed PK TRT model could serve as a tool to compare the relative dosimetric effectiveness of existing TRT agents and novel TRT agents early in the developmental phase to potentially reject those that possess unfavorable PKs.

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Section: Introductionmentioning

confidence: 99%

Dosimetric Effectiveness of Targeted Radionuclide Therapy Based on a Pharmacokinetic Landscape

Grudzinski

Burnette

Weichert

et al. 2010

Cancer Biotherapy and Radiopharmaceuticals

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“…The PK model is based on a two-compartment model originally established to calculate creatinine clearance (Sapirstein et al 1955), but frequently used also as a reference method for MAG3 clearance calculations (Dagli et al 1997, Bubeck et al 1990, Taylor et al 1988, Curti et al 1998. In this work, the model was extended to account for hepatic uptake and the transport of activity within the kidneys and the urinary tract.…”

Section: Discussionmentioning

confidence: 99%

“…Bubeck et al (1990) applied this model to analyse MAG3 pharmacokinetics, and arrived at an estimated distribution volume of approximately seven litres, evenly divided between the two compartments. The twocompartment model has been used as a reference for clearance calculations in a number of studies (Bubeck et al 1990, Taylor et al 1988, Curti et al 1998 and provides sufficiently realistic plasma 99m Tc-MAG3 concentration curves to constitute a suitable framework for a whole-body PK model.…”

Section: Introductionmentioning

confidence: 99%

Dynamic^99mTc-MAG3 renography: images for quality control obtained by combining pharmacokinetic modelling, an anthropomorphic computer phantom and Monte Carlo simulated scintillation camera imaging

Brolin¹,

Gleisner²,

Ljungberg³

2013

Phys. Med. Biol.

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In dynamic renal scintigraphy, the main interest is the radiopharmaceutical redistribution as a function of time. Quality control (QC) of renal procedures often relies on phantom experiments to compare image-based results with the measurement setup. A phantom with a realistic anatomy and time-varying activity distribution is therefore desirable. This work describes a pharmacokinetic (PK) compartment model for (99m)Tc-MAG3, used for defining a dynamic whole-body activity distribution within a digital phantom (XCAT) for accurate Monte Carlo (MC)-based images for QC. Each phantom structure is assigned a time-activity curve provided by the PK model, employing parameter values consistent with MAG3 pharmacokinetics. This approach ensures that the total amount of tracer in the phantom is preserved between time points, and it allows for modifications of the pharmacokinetics in a controlled fashion. By adjusting parameter values in the PK model, different clinically realistic scenarios can be mimicked, regarding, e.g., the relative renal uptake and renal transit time. Using the MC code SIMIND, a complete set of renography images including effects of photon attenuation, scattering, limited spatial resolution and noise, are simulated. The obtained image data can be used to evaluate quantitative techniques and computer software in clinical renography.

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“…A compartmental representation can provide either a detailed description of some kidney functions or nephron segments [73][74][75][76][77] or an integrated representation of the renal/body-fluid system [77,78]. Various models taking into account tubular mechanisms of secretion and accumulation [79], or including renal and non-renal elimination pathways have been built [80][81][82]. However, multi-compartmental models in contrast-enhanced MRI remain rarely used.…”

Section: Multi-compartmental Modelsmentioning

confidence: 99%

Analysis of contrast-enhanced MR images to assess renal function

Michoux

Vallée

Péchère-Bertschi

et al. 2006

Magn Reson Mater Phy

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The image analysis and kinetic modeling methods used in dynamic contrast-enhanced magnetic resonance imaging of the kidney are reviewed. Image analysis includes various techniques of coregistration and segmentation. Few methods have been completely implemented. Nevertheless, the use of coregistration may become a standard to decrease the effect of motion on abdominal images and improve the quality of the renal signals. Kinetic models are classified into three categories: enhancement-based, external and internal representations. Enhancement-based representations are limited to a basic analysis of the tracer concentration curves in the kidneys. Their relationship to the underlying physiology is complex and undefined. However, they can be used to evaluate the split renal function. External representations assess the kidney input and output. An external representation based on the up-slope of the renal enhancement to calculate the renal perfusion is commonly used because of its simplicity. In contrast, external representation based on deconvolution or identification methods remain underexploited. For glomerular filtration, an internal representation based on a two-compartmental model is mostly used. Internal representations based on multi-compartmental models describe the renal function in a more realistic way. Because of their numerical complexity, these models remain rarely used.

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A theoretical four-compartment model to evaluate separate kidney technetium-99m-MAG3 kinetics in humans

Cited by 4 publications

References 17 publications

Dosimetric Effectiveness of Targeted Radionuclide Therapy Based on a Pharmacokinetic Landscape

Dosimetric Effectiveness of Targeted Radionuclide Therapy Based on a Pharmacokinetic Landscape

Dynamic^99mTc-MAG3 renography: images for quality control obtained by combining pharmacokinetic modelling, an anthropomorphic computer phantom and Monte Carlo simulated scintillation camera imaging

Analysis of contrast-enhanced MR images to assess renal function

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A theoretical four-compartment model to evaluate separate kidney technetium-99m-MAG3 kinetics in humans

Cited by 4 publications

References 17 publications

Dosimetric Effectiveness of Targeted Radionuclide Therapy Based on a Pharmacokinetic Landscape

Dosimetric Effectiveness of Targeted Radionuclide Therapy Based on a Pharmacokinetic Landscape

Dynamic99mTc-MAG3 renography: images for quality control obtained by combining pharmacokinetic modelling, an anthropomorphic computer phantom and Monte Carlo simulated scintillation camera imaging

Analysis of contrast-enhanced MR images to assess renal function

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Dynamic^99mTc-MAG3 renography: images for quality control obtained by combining pharmacokinetic modelling, an anthropomorphic computer phantom and Monte Carlo simulated scintillation camera imaging