# Project 2: Enhancement of Biokinetics using Physiologically-Based Models for Internalized Radionuclides

> **NIH NIH P01** · NORTHWESTERN UNIVERSITY · 2022 · $374,453

## Abstract

PROJECT 2: ABSTRACT
Following mass population exposures from radiological or nuclear (RN) events, radionuclide biokinetic models
can be used to determine the time-dependent activity concentrations of internalized radionuclides in various
tissues and organs of the body as needed for dose assessment during triage. RN events may include
radionuclide releases from a radiological dispersion device, an improvised nuclear device, or a nuclear reactor
accident event. Biokinetic models from the International Commission on Radiological Protection (ICRP) are
currently implemented as deterministic (i.e., single “reference”) compartment-based models developed primarily
for occupational radiation protection purposes. We hypothesize that new biokinetic models with realistic RN
source term parameters and metabolic variability representative of an exposed population can be used to reliably
predict radionuclide biodistribution and responses at different levels of biological organization. The overall goal
of Project 2 is to integrate physiologically-based models of radionuclide intake and systemic biokinetics with
stochastic probability distributions of key model parameters. The core challenge in constructing realistic
biokinetic models representative of an exposed non-reference population is the lack of consideration of basic
physiological processes, from defining realistic source terms from RN events and translation to mechanistic
parameters that define inhalation intake kinetics, uptake into blood, and excretion. The proposed expansion in
biokinetic modeling will for the first time allow in-vivo assay and prediction of the efficacy of novel decorporation
agents in humans following an acute RN uptake for a representative population. Primary elements of innovation
in Project 2 include: (1) Development of biokinetic models specific to realistic RN sources; (2) Conducting
stochastic analysis of ICRP 133 Human Respiratory Tract Model for realistic RN source term and biokinetic
behavior; (3) Development of inhalation dose coefficients for exposed population (age/sex/morphometry-
specific) from realistic exposure source terms; (4) Construction of computational fluid and particle dynamics
(CFPD)-based physiological mouth-lung model of particle intake using realistic source terms and measurement
data of particulate distribution in the lungs; (5) Employment of machine learning with physiologically-based
pharmacokinetic models to determine the time-dependent uptake, retention, excretion, and reconstruction of
radionuclides to evaluate the efficacy of decorporation countermeasure agents; and (6) Development of an in-
vivo radiological triage body scanning system correlated with stochastic biokinetics for intake reconstruction and
monitoring of decorporation therapy. The proposed work will support Project 1 software in providing non-
reference inhalation dose coefficients, as well as detector efficiency whole body response functions for triage.
Project 1 and 3 data will be l...

## Key facts

- **NIH application ID:** 10327397
- **Project number:** 1P01AI165380-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Shaheen Azim Dewji
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $374,453
- **Award type:** 1
- **Project period:** 2022-03-10 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327397

## Citation

> US National Institutes of Health, RePORTER application 10327397, Project 2: Enhancement of Biokinetics using Physiologically-Based Models for Internalized Radionuclides (1P01AI165380-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10327397. Licensed CC0.

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