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Vol. 1 No. 2 (2024)

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January 20, 2026
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December 31, 2024

Copyright (c) 2024 Hamad Abdulelah H Alkhayyal, AMAL Ibrahim Samah Alruwaili, Mohammed Mousa Muyidi, Mousa Mohammed Ali Bahkali, Raef Abdu Ahmad Kamli, Sami Musaad Alotaibi, Maher Omran Ali Alotaibi, Dalal Ali Saleh Almadeh, Talal Mubarak Shuraim Al-Mughairi, Ibrahim Mohamed Hamed Somaily, Amani Ayeed Madee Alshahrani, Meshal Muflih Almutairi, Maryam Mohammed harthi

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Quantitative Imaging Biomarkers for Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling in Clinical Trials: A Review of Methodologies and Applications

https://doi.org/10.64483/202412553
Hamad Abdulelah H Alkhayyal
King Salman Hospital, Ministry of Health, Saudi Arabia
AMAL Ibrahim Samah Alruwaili
Sakaka – Al Jouf Region,Maternity and Children's Hospital, Ministry of Health , Saudi Arabia
Mohammed Mousa Muyidi
Abu Arish General Hospital, Ministry of Health, Saudi Arabia
Mousa Mohammed Ali Bahkali
Jazan Health Affairs, Saudi Ministry of Health, Saudi Arabia
Raef Abdu Ahmad Kamli
King Fahad Central Hospital, Jazan, Ministry of Health, Saudi Arabia
Sami Musaad Alotaibi
Afif Hospital, Ministry of Health , Saudi Arabia
Maher Omran Ali Alotaibi
Afif Hospital, Ministry of Health , Saudi Arabia
Dalal Ali Saleh Almadeh
Afif Hospital, Ministry of Health , Saudi Arabia
Talal Mubarak Shuraim Al-Mughairi
Afif General Hospital, Ministry of Health, Saudi Arabia
Ibrahim Mohamed Hamed Somaily
Altwal General Hospital, Ministry of Health, Saudi Arabia
Amani Ayeed Madee Alshahrani
King Abdullah Hospital, Bisha, Ministry of Health, Saudi Arabia
Meshal Muflih Almutairi
Al-Mithnab General Hospital, Ministry of Health , Saudi Arabia
Maryam Mohammed harthi
Imam Abdulrahman Al-Faisal Hospital, Ministry of Health , Saudi Arabia

Corresponding Author(s) : Hamad Abdulelah H Alkhayyal

halkhayyal@moh.gov.sa

Saudi Journal of Medicine and Public Health, Vol. 1 No. 2 (2024)

Abstract

Background: The high cost and failure rate of late-stage oncology and neurology drug trials underscore the critical need for robust early-phase decision-making tools. Traditional pharmacokinetic/pharmacodynamic (PK/PD) modeling, which relates drug exposure to a biological effect, often relies on plasma drug levels and sparse tissue biopsies, providing an incomplete picture of in vivo drug behavior and heterogeneity. Concurrently, advancements in medical imaging have moved beyond qualitative assessment to provide repeatable, non-invasive, and spatially resolved quantitative data on tumor morphology, cellularity, perfusion, and metabolism.


Aim: This narrative review aims to analyze the convergence of these two fields by examining how quantitative imaging biomarkers (QIBs) are integrated into PK/PD modeling frameworks within clinical trials. 


Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science for English-language articles (2010-2024). 


Results: QIBs from modalities like Dynamic Contrast-Enhanced MRI (DCE-MRI), Diffusion-Weighted Imaging (DWI), and Positron Emission Tomography (PET) provide critical parameters (e.g., Ktrans, ADC, SUV) that can populate computational PK/PD models. These imaging-informed models enable the non-invasive estimation of drug delivery to tissues, receptor occupancy, and the time-course of pharmacologic effect, offering a powerful tool for dose selection, go/no-go decisions, and patient stratification in early-phase trials. However, significant challenges in standardization, validation, and regulatory acceptance persist.


Conclusion: The integration of QIBs into PK/PD modeling represents a transformative paradigm in translational drug development. It bridges molecular pharmacology and in vivo imaging, enabling a more holistic, mechanistic understanding of drug action. For this potential to be fully realized, concerted efforts in technical standardization, robust biomarker qualification, and the development of shared computational frameworks are urgently needed.

Keywords

Quantitative Imaging Biomarkers; Pharmacokinetic-Pharmacodynamic Modeling; Clinical Trials; Surrogate Endpoints; Translational Medicine.
Alkhayyal, H. A. H., AMAL Ibrahim Samah Alruwaili, Mohammed Mousa Muyidi, Mousa Mohammed Ali Bahkali, Raef Abdu Ahmad Kamli, Sami Musaad Alotaibi, … Maryam Mohammed harthi. (2024). Quantitative Imaging Biomarkers for Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling in Clinical Trials: A Review of Methodologies and Applications. Saudi Journal of Medicine and Public Health, 1(2), 1943–1949. https://doi.org/10.64483/202412553
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Mousa Mohammed Ali Bahkali, Jazan Health Affairs, Saudi Ministry of Health
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