Abstract
Abstract
Objective. To construct an analytical model instead of local effect modeling for the prediction of the biological effectiveness of nanoparticle radiosensitization. Approach. An extended local effects model is first proposed with a more comprehensive description of the nanoparticles mediated local killing enhancements, but meanwhile puts forward challenging issues that remain difficult and need to be further studied. As a novel method instead of local effect modeling, a survival modification framework of compound Poisson additive killing is proposed, as the consequence of an independent additive killing by the assumed equivalent uniform doses of individual nanoparticles per cell under the LQ model. A compound Poisson killing (CPK) model based on the framework is thus derived, giving a general expression of nanoparticle mediated LQ parameter modification. For practical use, a simplified form of the model is also derived, as a concentration dependent correction only to the α parameter, with the relative correction (α″/α) dominated by the mean number, and affected by the agglomeration of nanoparticles per cell. For different agglomeration state, a monodispersion model of the dispersity factor η = 1, and an agglomeration model of 2/3 < η < 1, are provided for practical prediction of (α″/α) value respectively. Main results. Initial validation by the radiosensitization of HepG2 cells by carbon dots showed a high accuracy of the CPK model. In a safe range of concentration (0.003–0.03 μg μl−1) of the carbon dots, the prediction errors of the monodispersion and agglomeration models were both within 2%, relative to the clonogenic survival data of the sensitized HepG2 cells. Significance. The compound Poisson killing model provides a novel approach for analytical prediction of the biological effectiveness of nanoparticle radiosensitization, instead of local effect modeling.
Funder
National Natural Science Foundation of China
Science and Technology Commission of Shanghai Municipality
Subject
Radiology, Nuclear Medicine and imaging,Radiological and Ultrasound Technology
Reference85 articles.
1. Combination of gold nanoparticles with low-LET irradiation: an approach to enhance DNA DSB induction in HT29 colorectal cancer stem-like cells;Abbasian;J. Cancer Res. Clin. Oncol.,2019
2. Assessment of metallic nanoparticles as radioenhancers in gastric cancer therapy by Geant4 simulation and local effect model;Batooei;Nucl. Instrum. Methods B,2021
3. Radiation nanosensitizers in cancer therapy-from preclinical discoveries to the outcomes of early clinical trials;Bilynsky;Bioeng. Transl. Med.,2022
4. NBTXR3,a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial;Bonvalot;Lancet Oncol.,2019a
5. High Z nanoparticles and radiotherapy: a critical view - authors’ reply;Bonvalot;Lancet Oncol.,2019b