Localized radiotherapy of solid tumors using radiopharmaceutical loaded implantable system: insights from a mathematical model

Anahita Piranfar; Mohammad Souri; Arman Rahmim; Madjid Soltani

doi:10.3389/fonc.2024.1320371

Localized radiotherapy of solid tumors using radiopharmaceutical loaded implantable system: insights from a mathematical model

Front Oncol. 2024 Feb 26:14:1320371. doi: 10.3389/fonc.2024.1320371. eCollection 2024.

Authors

Anahita Piranfar¹, Mohammad Souri², Arman Rahmim^{3

4}, Madjid Soltani^{1

4

5

6

7}

Affiliations

¹ Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran.
² Department of NanoBiotechnology, Pasteur Institute of Iran, Tehran, Iran.
³ Departments of Radiology and Physics, University of British Columbia, Vancouver, BC, Canada.
⁴ Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada.
⁵ Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON, Canada.
⁶ Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON, Canada.
⁷ Centre for Sustainable Business, International Business University, Toronto, ON, Canada.

Abstract

Introduction: Computational models yield valuable insights into biological interactions not fully elucidated by experimental approaches. This study investigates an innovative spatiotemporal model for simulating the controlled release and dispersion of radiopharmaceutical therapy (RPT) using ¹⁷⁷Lu-PSMA, a prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical, within solid tumors via a dual-release implantable delivery system. Local delivery of anticancer agents presents a strategic approach to mitigate adverse effects while optimizing therapeutic outcomes.

Methods: This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored.

Results: Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (K_D) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×10⁷, 7.1×10⁸, and 7.1×¹⁰⁹ [Bq]) indicates that an activity of 7.1×10⁸ [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues.

Discussion: These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing.

Keywords: 177 Lu-PSMA; implantable drug delivery system; mathematical model; prostate cancer; radiopharmaceutical therapy.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors acknowledge funding in part by the Canadian Institutes of Health Research (CIHR) Project Grant PJT-162216.