Ultrasound-Assisted Radiopharmaceutical Investigation of GNL1-Mediated AKT-P53-P21 Axis Activation in Cervical Cancer Progression.

IF 1.7 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Cancer Biotherapy and Radiopharmaceuticals Pub Date : 2026-04-09 DOI:10.1177/10849785261438424

Yingying Jiang, Jing Ren, Junzhen Tao

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引用次数: 0

Abstract

Background: Cervical cancer is a leading cause of cancer death in women worldwide, and the outcomes for advanced or recurrent disease remain poor. Ultrasound-assisted delivery could increase intratumoral uptake of radiopharmaceuticals, but prospective clinical evidence and risk data are limited.

Methods: In a single-center pilot (n = 30), patients with advanced cervical cancer underwent paired PET/CT sessions 60 min after identical intravenous radiopharmaceutical injections: control (no ultrasound) and ultrasound-assisted delivery using 1 MHz focused ultrasound (FUS) for 10 min with microbubble cavitation monitoring. Uptake (SUV_max) and tumor-to-background ratio (TBR) were compared within patient; response used RECIST 1.1, and adverse events (AEs) used CTCAE v5.0. Paired biopsies quantified GNL1, phospho-AKT, p53, and p21 (H-score).

Results: Ultrasound increased median index-lesion SUV_max by ∼28% (p < 0.001) with improved TBR. The objective response rate was 26.7% and the disease control rate was 76.7%. Median progression-free survival was 8.5 months (95% confidence interval, 6.2-11.8) and the 12-month overall survival was 75% (median not reached). Most AEs were Grades 1-2; 20% were Grade ≥3, with no treatment-related deaths. Post-ultrasound biopsies showed decreased GNL1 and phospho-AKT with increased p53 and p21, and Δp21 correlated with uptake gain.

Conclusions: Nonablative FUS can safely enhance radiopharmaceutical uptake in cervical cancer and is associated with biomarker shifts consistent with p53/p21 pathway activation.

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超声辅助下gnl1介导的AKT-P53-P21轴激活在宫颈癌进展中的放射药物研究

背景：宫颈癌是全世界妇女癌症死亡的主要原因，晚期或复发疾病的预后仍然很差。超声辅助分娩可增加肿瘤内放射性药物的摄取，但前瞻性临床证据和风险数据有限。方法：在单中心试验中（n = 30），晚期宫颈癌患者在相同的静脉注射放射性药物后60分钟接受配对PET/CT治疗：对照（无超声）和超声辅助分娩（使用1 MHz聚焦超声（FUS） 10分钟，并监测微泡空化）。比较患者体内的摄取（SUVmax）和肿瘤与背景比（TBR）；不良事件（ae）采用CTCAE v5.0。配对活检量化GNL1、磷酸化akt、p53和p21 （H-score）。结果：超声改善TBR，使中位指数-病变SUVmax增加约28% （p < 0.001）。客观有效率为26.7%，疾病控制率为76.7%。中位无进展生存期为8.5个月（95%可信区间为6.2-11.8），12个月总生存期为75%（未达到中位）。大多数ae是1-2级；20%为≥3级，无治疗相关死亡。超声后活检显示GNL1和磷酸化akt降低，p53和p21升高，Δp21与摄取增益相关。结论：非消融性FUS可以安全地增强宫颈癌的放射性药物摄取，并与p53/p21通路激活的生物标志物转移相关。

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

Cancer Biotherapy and Radiopharmaceuticals 医学-核医学

CiteScore

7.80

自引率

2.90%

发文量

审稿时长

3 months

期刊介绍： Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies. The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.