Model identification and estimation of organ-function parameters using radioactive tracers and the impulse-response function

Szabó, Zsolt; Vosberg, H.; Sondhaus, C. A.; Feinendegen, L. E.

doi:10.1007/bf00279082

Cited by 21 publications

(14 citation statements)

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“…As already pointed out by Szabo et al [15], the use of impulse-response functions in connection with Laplace transform both simplifies and generalises model formulation. The underlying experimental design has two limitations: first, the observation time of 20 min, which is dictated by the radioactive decay of the 13 N isotope, and second, the fact that the main components of 13 (Fig.…”

Section: Discussionmentioning

confidence: 94%

“…The simple rules of connecting subsystems illustrated in Fig. 2, integration ( ), differentiation, (where f(0) is the initial condition in the time domain) and transformation of exponential functions, L[ae −bt ]=a/(s+b), make this approach very useful in drug and tracer kinetics [9,12,15,17]. Note that in certain cases (e.g.…”

Section: Laplace Transformationmentioning

confidence: 99%

“…The latter is the impulse response of the single-pass system (e.g. [15]), i.e. the normalised outflow profile (Fig.…”

Section: Mathematical Modelmentioning

confidence: 99%

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Determinants of [ 13 N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model

Weiß

Roelsgaard

Bender

et al. 2002

European Journal of Nuclear Medicine and Molecular Imaging

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The aim of this study was the development of a modelling approach for the analysis of the systemic kinetics of the tracer nitrogen-13 ammonia administered for dynamic liver scanning. The radioactive half-life of this tracer is 9.8 min, which limits the time span in which data are available in a positron emission tomography experimental setting. A circulatory pharmacokinetic model was applied to the metabolism of ammonia in anaesthetised pigs, which incorporated data from serial measurements of [(13)N]ammonia and [(13)N]metabolite activity in arterial and portal venous blood together with blood flow rates through the portal vein and through the hepatic artery obtained over 20 min after intravenous injection of [(13)N]ammonia. Model analysis showed that up to 20 min after injection the time course of [(13)N]ammonia concentration in arterial blood is primarily determined by distribution kinetics (steady-state volume of distribution 1,856+/-531 ml kg(-1)). Simultaneous fitting of arterial ammonia and metabolite blood concentrations allowed for estimation of the hepatic [(13)N]ammonia clearance (10.25+/-1.84 ml min(-1) kg(-1)), which accounted for the formation of the circulating metabolites.

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Section: Discussionmentioning

confidence: 94%

Section: Laplace Transformationmentioning

confidence: 99%

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Determinants of [ 13 N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model

Weiß

Roelsgaard

Bender

et al. 2002

European Journal of Nuclear Medicine and Molecular Imaging

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“…To account for variances in radioligand administration, metabolism, and recirculation, the TACs were processed by least-squares deconvolution analysis using the arterial input function, 40 which resulted in a standardized TAC called the impulse response function. 41 …”

Section: Pet Scan Processingmentioning

confidence: 99%

Positron-Emission Tomography Imaging of the Angiotensin II Subtype 1 Receptor in Swine Renal Artery Stenosis

Xia¹,

Seckin²,

Xiang³

et al. 2008

Hypertension

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Abstract-The angiotensin II subtype 1 receptor (AT 1 R) has been linked to the development and progression of renovascular hypertension. In this study we applied a pig model of renovascular hypertension to investigate the AT 1 R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT 1 R PET measurements were performed with the radioligand [ 11 C]KR31173 in 11 control pigs and in 13 pigs with hemodynamically significant renal artery stenosis; 4 were treated with lisinopril for 2 weeks before PET imaging. The radioligand impulse response function was calculated by deconvolution analysis of the renal time-activity curves. Key Words: positron-emission tomography Ⅲ angiotensin AT 1 receptor Ⅲ swine Ⅲ animal models Ⅲ renovascular hypertension R enovascular hypertension is the most common type of secondary hypertension that occurs in 2 to 4 million people in the United States. The renin-angiotensin system and its component, the angiotensin II subtype 1 receptor (AT 1 R), have been tightly linked to the development and progression of renovascular hypertension (RVH), but experimental mechanistic evidence for regulation of the AT 1 R has not been established in vivo. Antagonists against the angiotensin-converting enzyme (ACE; ACE inhibitors) or the AT 1 R (angiotensin receptor blockers) continue to play a key role in the therapy of renal hypertension and other kidney diseases. 1 Both drugs represent a "doubleedged sword," because they may deactivate regulatory effects of the renin-angiotensin system and the AT 1 R and trigger irreversible renal damage. 2 The complexity of the management of RVH raises a pressing need for an in vivo imaging technique that cannot only demonstrate reduced blood flow to the organ but also detect and monitor renal ischemia at the molecular level. [3][4][5][6] Magnetic resonance (MR) angiography (MRA) and computed tomography angiography are oriented toward depicting anatomy rather than tissue injury. 7,8 Radionuclide captopril renography has not been widely accepted 9 because of its limited accuracy in the presence of bilateral disease 10 or therapy with ACE inhibitors. 11 Inhibiting the activity of the AT 1 R with angiotensin receptor blockers or ACE inhibitors, on the other hand, is widely adapted by clinicians to protect the kidney from renal injury. [12][13][14][15][16] Probing molecular changes is expected to assist diagnosis and support prediction and evaluation of treatment success. We have identified the AT 1 R as a significant molecular imaging target because of its intricate involvement in the many aspects of renal physiology and pathology, [17][18][19] particularly in acute, subacute, and chronic complications of renal ischemia. 20,21 The AT 1 R is a key injury response protein because its continuing activation leads to stimulation of the extracellular matrix, 22 collagen deposition, glomerular remodeling, 23 inflammation, 24 apoptosis, 25 generation of oxygen species, and cell cycle arrest. 26 To this end, our group has synthesized several ...

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“…The distribution volume of the radioligand was calculated from these data using Logan's graphical method [15]. Selection of the most appropriate graphical method was based on the impulse response function that was obtained by deconvolution analysis [16]. The model was also confirmed by the fact that the Gjedde-Patlak plot resulted in an imperfect graphical fit [17,18].…”

Section: Quantification Of Radiotracer Bindingmentioning

confidence: 99%

PET Imaging of the AT1 receptor with [11C]KR31173

Zober

Mathews

Seckin

et al. 2006

Nuclear Medicine and Biology

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The goal of this study was to investigate the binding characteristics of [ 11 C]KR31173 and its applicability for PET studies of the AT 1 receptor (AT 1 R). Methods-Exvivo biodistribution and pharmacology were tested in mice. PET imaging was performed in mice, beagle dogs, and a baboon. To assess nonspecific binding, PET imaging was performed both before and after pretreatment with a potent AT 1 R antagonist. In the baboon, PET imaging was also performed with the previously developed radioligand [ 11 C]L-159,884 for comparison.Results-Ex vivo biodistribution studies in mice showed specific binding rates of 80-90% in the adrenals, kidneys, lungs, and heart. Specific binding was confirmed in mice using small animal PET. In dogs, renal cortex tissue concentration at 75-95 min post-injection was 63 nCi/mL/mCi at a specific binding rate of 95%. In the baboon renal cortex, tissue activity at 55-75 min post injection was 345 nCi/mL/mCi. The specific binding of [ 11 C]KR31173 was higher (81%) in the baboon than the specific binding of [ 11 C]L-159,884 (34%). Conclusion-[11 C]KR31173 shows accumulation and significant specific binding to the AT 1 R in the kidneys of mice, dogs, and baboon. These findings suggest that this radioligand is suited for imaging the renal cortical AT 1 R in multiple species.

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Model identification and estimation of organ-function parameters using radioactive tracers and the impulse-response function

Cited by 21 publications

References 80 publications

Determinants of [ 13 N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model

Determinants of [ 13 N]ammonia kinetics in hepatic PET experiments: a minimal recirculatory model

Positron-Emission Tomography Imaging of the Angiotensin II Subtype 1 Receptor in Swine Renal Artery Stenosis

PET Imaging of the AT1 receptor with [11C]KR31173

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