Optical-magnetic Imaging for Optimizing Lymphodepletion-TIL Combination Therapy in Breast Cancer.

IF 2.5 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-04-01 Epub Date: 2025-02-05 DOI:10.1007/s11307-025-01985-7

Jiaqian Li, Lishuang Guo, Yuan Feng, Guanghui Li, He Sun, Wei Huang, Jie Tian, Yang Du, Yu An

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Abstract

Purpose: Lymphodepletion before tumor-infiltrating lymphocytes (TIL) infusion can activate the immune system, enhance the release of homeostatic cytokines, and decrease the number of immunosuppressive cells. This process is crucial for improving the therapeutic efficacy of TIL therapy. However, the challenge of in vivo assessing TILs targeting tumors limits the optimization of lymphodepleting conditioning regimen (LDC).

Procedures: This study aims to employ magnetic particle imaging (MPI) and fluorescence molecular imaging (FMI) to monitor TIL biodistribution in vivo and optimize LDC in triple-negative breast cancer TIL therapy. MPI provides quantitative imaging capabilities without depth limitations, effectively complementing the high sensitivity of FMI. The efficacy of different LDCs in enhancing TIL therapy was assessed using FMI, and MPI quantified the number of TILs accumulated in the 4T1 tumor.

Results: TILs preserved viability, phenotypes, and anti-tumor efficacy after being labeled with superparamagnetic iron oxide and fluorescence dye DiR. The dual-modality imaging system effectively discerned variations in LDC treatments that enhanced TIL therapy. Compared to TIL monotherapy, lymphodepletion with TIL therapy improves tumor dual-modality imaging signal intensity, increases the expression of monocyte chemotactic protein-1 in serum and tumor tissue, and enhances the therapeutic effect of TILs.

Conclusion: Our results confirm the utility of optical-magnetic dual-modality imaging for tracking the biodistribution of TILs in vivo. With the help of optical-magnetic dual-modality imaging, we successfully optimize TIL combination therapy. Optical-magnetic dual-modality imaging provides a new approach to develop personalized immunotherapy strategies and mine potential therapeutic mechanisms for TIL.

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光磁成像优化淋巴细胞耗尽- til联合治疗乳腺癌。

目的：肿瘤浸润淋巴细胞（TIL）输注前淋巴细胞清除可激活免疫系统，增强稳态细胞因子的释放，减少免疫抑制细胞的数量。这一过程对于提高TIL治疗的疗效至关重要。然而，体内评估靶向肿瘤的TILs的挑战限制了淋巴消耗调节方案（LDC）的优化。程序：本研究旨在利用磁颗粒成像（MPI）和荧光分子成像（FMI）监测TIL在体内的生物分布，并优化三阴性乳腺癌TIL治疗中的LDC。MPI提供了不受深度限制的定量成像能力，有效地补充了FMI的高灵敏度。使用FMI评估不同LDCs增强TIL治疗的疗效，MPI量化4T1肿瘤中积累的TIL数量。结果：经超顺磁性氧化铁和荧光染料DiR标记后，TILs保留了活力、表型和抗肿瘤功效。双模成像系统有效地识别了ldcs治疗的变化，从而增强了TIL治疗。与TIL单药治疗相比，TIL淋巴耗损联合TIL治疗可改善肿瘤双模成像信号强度，提高血清和肿瘤组织中单核细胞趋化蛋白-1的表达，增强TIL的治疗效果。结论：我们的研究结果证实了光磁双模成像在体内追踪TILs生物分布的实用性。在光磁双模成像的帮助下，我们成功地优化了TIL联合治疗。光磁双模成像为TIL的个性化免疫治疗策略和潜在治疗机制的探索提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.

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