Preclinical Evaluation of 99mTc-Labeled LHRH Analog as Cancer Receptor Imaging.

IF 1.8 3区医学 Q3 ONCOLOGY

Oncology Pub Date : 2025-07-11 DOI:10.1159/000542823

Lucía Alfaya, Ximena Camacho, Mirel Cabrera, Marcos Tassano, Eduardo Savio, Laura Reyes, Andrea Paolino, María Fernanda García, Marcelo Fernández, Juan Pablo Gambini, Pablo Cabral

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引用次数: 0

Abstract

Introduction: Breast cancer is the main cause of cancer-related mortality in women in the developed world. In particular, receptors of luteinizing hormone-releasing hormone (LHRH or GnRH) are overexpressed in this malignant disease. The aim of this study was to develop a new molecular probe [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/nicotinic acid (NA) as a novel molecular imaging agent for breast cancer.

Methods: HYNIC-GSG-LHRH(D-Lys6) was acquired and radiolabeled with [99mTc]Tc. Radiochemical purity and stability under different conditions were evaluated by instant thin-layer chromatography (ITLC) and high-performance liquid chromatography. Lipophilicity was determined by the partition coefficient test. In vitro cell binding studies were performed in different human and mice breast cancer cell lines (MDA-MB-231, MDA-MB-435, MCF-7, BT474, and 4T1) as well as in normal murine fibroblasts (NIH-3T3) and CHO-K1 as a negative control. Biodistribution studies were performed in normal Balb/c mice and 4T1 tumor-bearing Balb/c mice up to 6 h post-injection (pi). SPECT/CT images were performed in 4T1 tumor-bearing Balb/c mice up to 5 h pi.

Results: [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/NA complex was labeled with a high radiochemical purity (>98%) and remained stable for up to 4 h. It exhibited good hydrophilicity (log p = -2.82 ± 0.04) and also demonstrated significant and specific binding across all evaluated breast cancer cell lines. Biodistribution studies showed a high renal clearance and low nonspecific binding (<2% Act/g) in most organs, as well as appreciable tumor uptake (5.8 ± 0.5 % ID/g 1 h pi) and high tumor-to-muscle ratio (maximum of 30.5 ± 11.2 at 1 h pi). SPECT/CT imaging of 4T1-tumor-bearing Balb/c mice revealed results consistent with the biodistribution studies, showing a tumor-to-non-tumor ratio of greater than 3.5 at all evaluated time points. In vivo blocking studies confirmed specificity for the LHRH receptor.

Conclusions: [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/NA complex has shown significant potential for in vivo visualization of LHRH receptors expression in breast cancer.

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99mtc标记的LHRH类似物作为癌症受体成像的临床前评价。

导言：乳腺癌是发达国家妇女癌症相关死亡的主要原因。特别是，黄体生成素释放激素受体（LHRH或GnRH）在这种恶性疾病中过度表达。本研究的目的是开发一种新的分子探针[99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/三氨酸/烟酸（NA）作为乳腺癌的新型分子显像剂。方法：获取HYNIC-GSG-LHRH(D-Lys6)，用[99mTc]Tc放射标记。采用即时薄层色谱法和高效液相色谱法对不同条件下放射线化学纯度和稳定性进行了评价。通过分配系数试验测定其亲脂性。在不同的人和小鼠乳腺癌细胞系（MDA-MB-231、MDA-MB-435、MCF-7、BT474和4T1）以及正常小鼠成纤维细胞（NIH-3T3）和CHO-K1作为阴性对照进行了体外细胞结合研究。在正常Balb/c小鼠和4T1荷瘤Balb/c小鼠中进行生物分布研究，直至注射后6小时（pi）。对4T1荷瘤Balb/c小鼠进行SPECT/CT成像，时间长达5h。结果：[99mTc] tc - hynice - gsg - lhrh (d-Lys6)/tricine/NA复合物具有高放射化学纯度（>98%），并保持稳定长达4小时。它具有良好的亲水性（log p = -2.82±0.04），并且在所有被评估的乳腺癌细胞系中都表现出显著的特异性结合。生物分布研究显示其具有较高的肾脏清除率和较低的非特异性结合(结论：[99mTc] tc - hynici - gsgg -LHRH(d-Lys6)/tricine/NA复合物在乳腺癌中显示出显著的体内可视化LHRH受体表达潜力。

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

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.