Biological Guided Carbon-Ion Microporous Radiation to Tumor Hypoxia Area Triggers Robust Abscopal Effects as Open Field Radiation.

Qingting Huang,Yun Sun,Lien-Chun Lin,Lin Kong,Weiwei Wang,Yangle Huang,Jiade Jay Lu,Xiaodong Wu,Jing Yang

doi:10.3389/fonc.2020.597702

Abstract

Recently, a growing number of studies focus on partial tumor irradiation to induce the stronger non-target effects. However, the value of partial volume carbon ion radiotherapy (CIRT) targeting hypoxic region of a tumor under imaging guidance as well as its effect of inducing radiation induced abscopal effects (RIAEs) have not been well investigated. Herein, we developed a technique of carbon ion microporous radiation (CI-MPR), guided by 18F-FMISO PET/computerized tomography (CT), for partial volume radiation targeting the hypoxia area of a tumor and investigated its capability of inducing abscopal effects. Tumor-bearing mice were inoculated subcutaneously with breast cancer 4T1 cells into the flanks of both hind legs of mouse. Mice were assigned to three groups: group I: control group with no treatment; group II: carbon ion open field radiation (CI-OFR group) targeting the entire tumor; group III: partial volume carbon ion microporous radiation (CI-MPR group) targeting the hypoxia region. The tumors on the left hind legs of mice were irradiated with single fraction of 20 Gy of CIRT. Mice treated with CI-MPR or CI-OFR showed that significant growth delay on both the irradiated and unirradiated of tumor as compared to the control groups. Tumor regression of left tumor irradiated with CI-OFR was more prominent as compared to the tumor treated with CI-MPR, while the regression of the unirradiated tumor in both CI-MPR and CI-OFR group was similar. Biological-guided CIRT using the newly developed microporous technique targeting tumor hypoxia region could induce robust abscopal effects similar to CIRT covering the entire tumor.

Highlights

The therapeutic effects of ionizing radiation are often limited by the hypoxia of tumors [1,2,3,4]
Regression of the unirradiated tumor on the right side in both CI-MPR and CI-OFR group was similar, and the fold change of the tumor volumes on day 15 in CIMPR was 1.1 times that of CI-OFR group (P>0.05), indicating that CI-MPR provided similar abscopal effects as CI-OFR. This phenomenon demonstrated that microporous carbon ion radiotherapy (CIRT) with a diameter of 1.5 mm targeting the hypoxic area could achieve similar abscopal effects as open field irradiation. This present study evaluated the anti-tumor effects triggered by carbon ion microporous radiation targeting hypoxic area with a single high dose on murine tumor model as compared to the conventional open-field tumor technique
The hypoxic area was visualized by 18F-FMISO Micro-PET/computerized tomography (CT) imaging, and the feasibility of the microporous irradiation technique was verified by the EBT3 film and an in vivo tumor model

Summary

Introduction

The therapeutic effects of ionizing radiation are often limited by the hypoxia of tumors [1,2,3,4]. The results of a growing number of in vitro and in vivo studies indicate that, in addition to the local therapeutic effects, radiation therapy may be in favor of changing the tumor microenvironments correlated with immunity and endothelial cells of the tumor micro-vasculatures, thereby inducing the nontarget effects, such as radiation induced bystander effects and abscopal effects (RIAEs) [10,11,12,13]. RIAEs are radiation induced effects in unirradiated tumors distant from irradiated target regresses. Both pre-clinical and clinical studies have confirmed the existence of abscopal effects and its potential antitumor effects [14,15,16]. The mechanisms through which irradiation exerts its immune modulation effects, are not well clarified

Methods

Results

Conclusion