Value of Multitracer Imaging in Hepatocellular Carcinomas with Different Metastatic Potential.

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

Molecular Imaging and Biology Pub Date : 2026-02-24 DOI:10.1007/s11307-026-02088-7

Tingting He, Cong Zhang, Jinming Zhang, Xiaojun Zhang, Ruimin Wang

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引用次数: 0

Abstract

Background: Hepatocellular carcinoma (HCC) shows marked heterogeneity and varying metastatic potential, challenging prognosis and treatment. This study evaluated multitracer PET imaging with [¹⁸F]FDG, [¹⁸F]FLT, and [¹⁸F]ACE to differentiate HCCs by metastatic behavior and explored its prognostic relevance.

Methods: Four human HCC cell lines with varying metastatic potential (HepG2, QGY7701, MHCC97-H, MHCC97-L) were assessed for in vitro tracer uptake, proliferation, and invasion. Subcutaneous and spontaneous metastasis models were established in nude mice. Tumor uptake of tracers was quantified via microPET/CT. mRNA expression of MMP9 and VEGFR-2 and survival were analyzed. Fisher's classifier was applied to compare single-, dual-, and triple-tracer datasets with cross-validation.

Results: Tracer uptake significantly differed among cell lines (p < 0.001). The triple-tracer model ([¹⁸F]FDG + [ ¹⁸F]FLT + [¹⁸F]ACE) yielded the lowest classification error rate (0.074) compared with dual tracers (0.085-0.362). In vivo, [¹⁸F]FDG uptake correlated with metastatic potential, MMP9 and VEGFR-2 expression (r = 0.770-0.830, p < 0.05), and inversely with survival (r = - 0.726, p = 0.005). There is a significant difference in FDG uptake values between high-metastatic and low-metastatic cell lines as well as in tumor model.[¹⁸F]FLT uptake showed moderate correlation with biomarkers but not with survival, while [¹⁸F]ACE had no significant discriminative value.

Conclusions: A multiparameter (multitracer) classification model had superior ability to discriminate four HCC cell lines with different biological behavior compared with dual tracers or single tracer through in vitro cell uptake experiment. [1⁸F]FDG uptake can distinguish between tumor models with high and low metastatic potential, and [1⁸F]FDG uptake can predict the survival time in metastatic models. [¹⁸F]FDG uptake probably be noninvasive prognostic marker, reflecting tumor heterogeneity and correlating with survival and metastasis-related biomarkers. This approach may aid in clinical stratification and personalized management of HCC.

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多示踪成像在不同转移潜能肝细胞癌中的价值。

背景：肝细胞癌（HCC）具有明显的异质性和不同的转移潜力，对预后和治疗具有挑战性。本研究评估了[18F]FDG、[18F]FLT和[18F]ACE的多示踪PET成像，以鉴别hcc的转移行为，并探讨其与预后的相关性。方法：对四种具有不同转移潜力的人肝癌细胞系（HepG2、QGY7701、MHCC97-H、MHCC97-L）进行体外示踪剂摄取、增殖和侵袭的评估。建立裸鼠皮下和自发转移模型。通过微pet /CT定量肿瘤对示踪剂的摄取。分析MMP9、VEGFR-2 mRNA表达与生存率的关系。采用Fisher分类器对单、双、三示踪剂数据集进行交叉验证比较。结果：不同细胞系间示踪剂摄取差异显著（p 18F]FDG + [18F] FLT + [18F]ACE）的分类错误率（0.074）低于双示踪剂（0.085-0.362）。在体内，[18F]FDG摄取与转移潜能、MMP9和VEGFR-2表达相关(r = 0.70 -0.830， p 18F]FLT摄取与生物标志物中度相关，但与生存无关，而[18F]ACE没有显著的判别价值。结论：通过体外细胞摄取实验，与双示踪剂或单示踪剂相比，多参数（多示踪剂）分类模型对四种不同生物学行为的HCC细胞系具有更好的区分能力。[1⁸F]FDG摄取可以区分高转移潜能和低转移潜能的肿瘤模型，[1⁸F]FDG摄取可以预测转移模型的生存时间。[18F]FDG摄取可能是非侵入性预后标志物，反映肿瘤异质性，并与生存和转移相关的生物标志物相关。这种方法有助于肝细胞癌的临床分层和个性化治疗。

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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.