Preclinical Evaluation of Novel SGLT2-Targeted Near-Infrared Optical Imaging Agent for Early-Stage Pulmonary Adenocarcinoma.

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

Molecular Imaging and Biology Pub Date : 2025-07-14 DOI:10.1007/s11307-025-02029-w

Katherine Ortmeyer Welch, Kelly Anne McGovern, Lydia Chen, Ryan Krouse, Kevin Guo, Jeffrey Huang, Michael Brown, Jake Mlakar, Venu Bandi, David Holt, Paul Zhang, Sunil Singhal

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引用次数: 0

Abstract

Purpose: Lung cancer is increasingly diagnosed at early stages, but intraoperative localization of early lesions remains challenging. Intraoperative molecular imaging (IMI) aids in localization of tumors during surgery; however, no optical agents are targeted specifically for early-stage lesions. The sodium-glucose cotransporter 2 (SGLT2) has been implicated in early lung carcinogenesis. This study aimed to describe SGLT2 expression in early-stage lung adenocarcinoma (LUAD) and develop and validate a novel SGLT2-targeted near-infrared (NIR) contrast agent, GlucoGlo, for imaging LUAD.

Procedures: SGLT2 expression was confirmed by immunohistochemistry (IHC) in human samples. GlucoGlo optical properties were characterized and compared to common NIR dyes. Sensitivity and specificity for SGLT2 were assessed using preclinical in vitro and in vivo mouse models.

Results: On IHC, stage I LUAD displayed higher SGLT2 expression than stage II-III LUAD and normal lung tissue. GlucoGlo exhibited similar depth of penetration and resolution to FDA-approved contrast agents. SGLT2-expressing cell lines treated with GlucoGlo displayed higher fluorescence than the control cell line, confirming SGLT2-dependent uptake. Fluorescence increased with both incubation time and GlucoGlo concentration. Glucose and unconjugated GlucoGlo ligand competitively inhibited GlucoGlo in a dose-dependent manner, indicating high affinity and specificity. GlucoGlo selectively accumulated in SGLT2-expressing flank xenografts, with mean SBR of 2.23 and was inhibited by pretreatment with unconjugated GlucoGlo ligand.

Conclusions: These findings support the potential of GlucoGlo as a targeted IMI contrast agent for early-stage LUAD, and they provide a foundation for future in vivo studies and translational development.

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新型sglt2靶向近红外光学显像剂对早期肺腺癌的临床前评价

目的：肺癌越来越多地在早期被诊断出来，但术中早期病变的定位仍然具有挑战性。术中分子成像（IMI）有助于术中肿瘤的定位；然而，没有一种光学试剂是专门针对早期病变的。钠-葡萄糖共转运蛋白2 （SGLT2）与早期肺癌发生有关。本研究旨在描述SGLT2在早期肺腺癌（LUAD）中的表达，并开发和验证一种新的SGLT2靶向近红外（NIR）造影剂GlucoGlo，用于LUAD成像。方法：免疫组化法（IHC）检测人标本中SGLT2的表达。对葡糖苷染料的光学性质进行了表征，并与普通近红外染料进行了比较。使用临床前体外和体内小鼠模型评估SGLT2的敏感性和特异性。结果：在IHC上，I期LUAD的SGLT2表达高于II-III期LUAD和正常肺组织。GlucoGlo表现出与fda批准的造影剂相似的渗透深度和分辨率。经GlucoGlo处理的表达sglt2的细胞系显示出比对照细胞系更高的荧光，证实了sglt2依赖性摄取。荧光随培养时间和葡萄糖浓度的增加而增加。葡萄糖和未缀合的GlucoGlo配体以剂量依赖的方式竞争性地抑制GlucoGlo，表明高亲和力和特异性。GlucoGlo选择性地在表达sglt2的侧翼异种移植物中积累，平均SBR为2.23，并且通过未结合的GlucoGlo配体预处理被抑制。结论：这些发现支持了GlucoGlo作为早期LUAD靶向IMI造影剂的潜力，并为未来的体内研究和转化开发提供了基础。

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.