A Proposed Blood Circulation Model for Reference Man

Rw, Leggett; Lr, Williams

doi:10.1097/00004032-199508000-00003

Cited by 95 publications

(72 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Connecting variables of unlabeled and labeled antibody system are total number of antigens in respective organ and physical decay of nuclide. (30). y Liver is supported by direct arterial flow (6.5% of total blood flow), plus portal flow from gastrointestinal tract (16%) plus flow from spleen (3%).…”

Section: Discussionmentioning

confidence: 99%

“…For the blood flow, F i , to the organs and the corresponding vascular volumes, the values of the blood circulation model for reference man were used (30). However, only vascular spaces, V i , of the organs of interest and of the gastrointestinal tract are explicitly implemented; other vascular spaces (e.g., veins, arteries, and heart) are merged into a single compartment.…”

Section: Model Developmentmentioning

confidence: 99%

See 1 more Smart Citation

Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model

Kletting¹,

Bunjes²,

Reske³

et al. 2009

J Nucl Med

View full text Add to dashboard Cite

Radioimmunotherapy is a method to selectively deliver radioactivity to cancer cells via specific antibodies. A strategy to enhance the efficacy of radioimmunotherapy is the prior application of unlabeled antibody, resulting in an increase in the dose to the target tissue and a decrease in the burden to other organs. It was suggested that optimizing this approach might considerably improve radioimmunotherapy with anti-CD45 antibody. The present work develops a physiologically based pharmacokinetic model to individually determine the optimal preload for radioimmunotherapy with the YAML568 anti-CD45 antibody for each patient. Methods: A physiologically based pharmacokinetic model was developed to describe the biodistribution of anti-CD45 antibody. The transport of antibody to the organs of interest via blood flow, competitive binding of unlabeled and labeled antibody, degradation and excretion of antibody, and physical decay were included in the model. The model was fitted to the biokinetics data of 5 patients with acute myeloid leukemia. On the basis of the estimated parameters, simulations for a 0-to 534-nmol preload of unlabeled antibody were conducted and the organ residence times were calculated. Results: The measured data could be adequately described by the constructed model. The estimated numbers of accessible antigens in the respective organ, in nanomoles, were 97 6 33 for red marrow, 49 6 24 for liver, 34 6 18 for spleen, 38 6 31 for lymph nodes, and 0.9 6 0.4 for blood. These ranges indicate high interpatient variability. The optimal amount of unlabeled antibody identified by simulations would improve the ratio of residence time in red marrow to residence time in liver by a factor of 1.6-2.4. Conclusion: The efficacy of radioimmunotherapy using anti-CD45 antibody can be considerably increased with the presented model. A more selective delivery of radioactivity to the target organ and a reduction in the toxicity to normal tissue are achieved by determining the optimal preload. Furthermore, the adverse effects of radioimmunotherapy might be drastically reduced while saving antibody expenses. The validation of the model is ongoing. The model is easily extendible and therefore most probably applicable to radioimmunotherapy of other hematologic malignancies, such as antibodies targeted to CD20, CD33, or CD66.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Model Developmentmentioning

confidence: 99%

Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model

Kletting¹,

Bunjes²,

Reske³

et al. 2009

J Nucl Med

View full text Add to dashboard Cite

show abstract

“…We defined regions of interest (ROIs) We account for the blood present in the organs, which contributes to the intensity of radioactivity of the studied organs. The blood volume per organ was obtained from Leggett and Williams (1995) who provide blood content in percentage of total blood volume for a reference middle-aged man. In the equations for intensity, we added the blood contribution when it could be substantial, i.e.…”

Section: Appendix : Pbpk Model Equationsmentioning

confidence: 99%

Development of a physiologically based kinetic model for 99m-Technetium-labelled carbon nanoparticles inhaled by humans

Péry

Brochot

Hoet

et al. 2009

Inhalation Toxicology

View full text Add to dashboard Cite

To cite this version:Alexandre Pery, Céline Brochot, Peter Hoet, Abderrahim Nemmar, Frédéric Y. Bois. Development of a physiologically based kinetic model for 99m-Technetium-labelled carbon nanoparticles inhaled by humans. Inhalation Toxicology, Taylor & Francis, 2009, 21 (13) analysis points to a likely translocation of particle-bound technetium from lung to blood, at a rate about 2-fold lower than the transfer rate of free technetium. Notably, restricting the model so that only free technetium would have been able to reach blood circulation result in much poorer fits to the experimental data. The percentage of small particles able to translocate was estimated at 12.7% of total particles. The percentage of unbound technetium was estimated at 6.7% of total technetium. To our knowledge, our model is the first PBPK model able to use imaging data to describe the absorption and distribution of nanoparticles. We believe that our modeling approach using Bayesian and MCMC techniques provides a reasonable description on which to base further model refinement.2

show abstract

“…Blood flow rates as percentage of cardiac output are given in the ICRP report (ICRP 2003) for the resting middle-aged male adult, based on a compilation of published data by Williams and Leggett (1989) and Leggett and Williams (1995). These data were used to calculate blood flow rates (L/h) for liver (arterial and portal flow), brain, kidney, adipose tissue (fat), muscle/skin and skeleton (without active bone marrow).…”

Section: Blood Flow To Organs and Tissuesmentioning

confidence: 99%

Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration

et al. 2004

View full text Add to dashboard Cite

When deriving health based exposure limits in recent years, attention has been drawn to susceptible subpopulations, in particular to children. We investigate the differences in kinetics between children and adults during inhalation of styrene as a typical category 3 volatile organic compound (VOC), i.e. a gas with a high rate of alveolar absorption (due to low reactivity and low water solubility). Internal exposure was simulated using a physiologically based kinetic model over a broad range of airborne concentrations (1 to 1000 ppm) and for an exposure time of up to eight hours according to the scenario in the acute exposure guideline level (AEGL) program. Age-specific anatomical and physiological parameters and compound-specific data were derived from the literature. The calculated concentrations in arterial blood are higher in children than in adults, and are highest in the newborn. For an 8-hour exposure to low concentrations, the calculated arterial concentration in the newborn is higher by a factor of 2.3 than in the adult. This is mainly due to the relatively high ventilation rate and the immature metabolism. With increasing airborne concentration, the ratio of arterial concentrations (newborn/adult) increases to a maximum of 3.8 at 130 ppm in ambient air, and declines with further increments of concentration to a value of 1.7. This is because the metabolism of the newborn becomes non-linear at lower concentrations than in adults. At high concentrations, metabolism is saturated in both age groups. For shorter exposures, the dose-dependency of the concentration ratios (newborn/adult) is less pronounced. This is the first article to show that the intraspecies uncertainty factor may vary with concentration and duration of exposure.

show abstract

A Proposed Blood Circulation Model for Reference Man

Cited by 95 publications

References 0 publications

Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model

Improving Anti-CD45 Antibody Radioimmunotherapy Using a Physiologically Based Pharmacokinetic Model

Development of a physiologically based kinetic model for 99m-Technetium-labelled carbon nanoparticles inhaled by humans

Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration

Contact Info

Product

Resources

About