Lucía Alfaya, Ximena Camacho, Mirel Cabrera, Marcos Tassano, Eduardo Savio, Laura Reyes, Andrea Paolino, María Fernanda García, Marcelo Fernández, Juan Pablo Gambini, Pablo Cabral
{"title":"99mtc标记的LHRH类似物作为癌症受体成像的临床前评价。","authors":"Lucía Alfaya, Ximena Camacho, Mirel Cabrera, Marcos Tassano, Eduardo Savio, Laura Reyes, Andrea Paolino, María Fernanda García, Marcelo Fernández, Juan Pablo Gambini, Pablo Cabral","doi":"10.1159/000542823","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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(<sc>d</sc>-Lys6)/tricine/nicotinic acid (NA) as a novel molecular imaging agent for breast cancer.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>[99mTc]Tc-HYNIC-GSG-LHRH(<sc>d</sc>-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.</p><p><strong>Conclusions: </strong>[99mTc]Tc-HYNIC-GSG-LHRH(<sc>d</sc>-Lys6)/tricine/NA complex has shown significant potential for in vivo visualization of LHRH receptors expression in breast cancer.</p>","PeriodicalId":19497,"journal":{"name":"Oncology","volume":" ","pages":"1-13"},"PeriodicalIF":1.8000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preclinical Evaluation of 99mTc-Labeled LHRH Analog as Cancer Receptor Imaging.\",\"authors\":\"Lucía Alfaya, Ximena Camacho, Mirel Cabrera, Marcos Tassano, Eduardo Savio, Laura Reyes, Andrea Paolino, María Fernanda García, Marcelo Fernández, Juan Pablo Gambini, Pablo Cabral\",\"doi\":\"10.1159/000542823\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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(<sc>d</sc>-Lys6)/tricine/nicotinic acid (NA) as a novel molecular imaging agent for breast cancer.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>[99mTc]Tc-HYNIC-GSG-LHRH(<sc>d</sc>-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. 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Preclinical Evaluation of 99mTc-Labeled LHRH Analog as Cancer Receptor Imaging.
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.
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.
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