HYPOTHESIS AND THEORY article
Front. Oncol.
Sec. Radiation Oncology
This article is part of the Research TopicRadiation Spatial Fractionation—A novel approach to integrate Physics, Biology, and Immunology for high therapeutic index radiotherapyView all 8 articles
Spatially Optimized 125I Brachytherapy: A Novel Immunomodulatory Approach Based on spatially fractionated radiation therapy(SFRT) Principles
Provisionally accepted
Qiyu Sun1,2*
Yanbo Hu1,2
Lulu Du1,2
Zhiqian Sun2
Rui Huang2Lichao Wang1
Zhenzhen Cui2
Jiaxin Yang2Xiaowen Ma2
Min LI2*- 1Jinzhou Medical University, Jinzhou, China
- 2PLA 960th Hospital, Jinan, China
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Conventional ¹²⁵I brachytherapy, emphasizing uniform dose coverage, may limit its potential to activate anti-tumor immunity. We propose integrating the principles of Spatially Fractionated Radiotherapy (SFRT) into ¹²⁵I brachytherapy. Through a heterogeneous dose design featuring "co-existing high-and low-dose regions", this approach aims to synergize immunogenic cell death (ICD) with the preservation of immune cell function, thereby transforming the tumor into an "in situ vaccine". The inherent characteristics of ¹²⁵I sources – namely, the steep dose gradient of their low-energy gamma rays and continuous low-dose-rate delivery – provide unique advantages for the precise construction of distinct regions: a high-dose zone (to induce ICD) and a low-dose zone (to support immune cell survival).We have established a novel dose evaluation framework (incorporating metrics such as HDRI [High-Dose Region Index], LDRI [Low-Dose Region Index], DGUI [Dose Gradient Utilization Index], and SHS [Spatial Heterogeneity Score]) to replace traditional homogeneous indices like D90/V100. Furthermore, we present optimization strategies for parameters including source spacing and source activity.Finally, we systematically outline an integrated preclinical-to-clinical research pathway for combination with immunotherapy. This lays the theoretical and experimental foundation for developing tumor-type-specific, personalized treatment protocols based on the "¹²⁵I-SFRT + Immunotherapy" approach.
Keywords: 125I Brachytherapy 1, Immunomodulatory 2, SFRT Principles 3, ICD 4, Tumors 5
Received: 27 Aug 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Sun, Hu, Du, Sun, Huang, Wang, Cui, Yang, Ma and LI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qiyu Sun
Min LI
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