[99mTc]Tc-labeled cyc-DX600-HYNIC as a SPECT probe for ACE2-specific pancreatic cancer imaging.

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
American journal of nuclear medicine and molecular imaging Pub Date : 2024-04-25 eCollection Date: 2024-01-01 DOI:10.62347/VFHT4078
Pan Zhou, Zheng Li, Danni Li, Shuai Xue, Rou Li, Lan Zhang, Qingyun Bai, Xiao Li
{"title":"[<sup>99m</sup>Tc]Tc-labeled cyc-DX600-HYNIC as a SPECT probe for ACE2-specific pancreatic cancer imaging.","authors":"Pan Zhou, Zheng Li, Danni Li, Shuai Xue, Rou Li, Lan Zhang, Qingyun Bai, Xiao Li","doi":"10.62347/VFHT4078","DOIUrl":null,"url":null,"abstract":"<p><p>As a regulator in renin-angiotensin-aldosterone system, angiotensin-converting enzyme 2 (ACE2) closely correlated with tumor progression of pancreatic cancer, meantime, was easily affected by a variety of factors. [<sup>99m</sup>Tc]Tc-cyc-DX600 SPECT was established as an ACE2-specific imaging protocol to figure out the ACE2 status in pancreatic tumor. BALB/C-NU mice were used to prepare the subcutaneous cell derived xenograft (CDX) models with HEK-293T or HEK-293T/hACE2 cells to validate ACE2 specificity of [<sup>99m</sup>Tc]Tc-cyc-DX600 SPECT and establish SPECT imaging protocol. On the basis of [<sup>99m</sup>Tc]Tc-cyc-DX600 SPECT and [<sup>18</sup>F]F-FDG PET/CT, ACE2-dependence on tumor size and tumor metabolism were further verified on orthotopic pancreatic cancer model with KPC cells. Immunohistochemical analysis was used to demonstrate the findings on ACE2 SPECT. [<sup>99m</sup>Tc]Tc-cyc-DX600 was of superior tumor uptake in HEK-293T/hACE2 CDX than wild type (6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL at 1.5 h post injection (p.i.); 3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL at 4.5 h p.i.). For the CDX models with PANC-1 cells, a significant negative correlation between the slope of tumor volume and tumor uptake was observed (r = -0.382 for the 1-4th day; r = -0.146 for the 1-5th day; r = -0.114 for the 1-6th day; r = -0.152 for the 1-7th day; but <i>P > 0.05</i> for all). For orthotopic pancreatic cancer model, the linear correlation between FDG PET and ACE2 SPECT of the pancreatic lesions was negative (r = -0.878), the quantitative values of ACE2 SPCET was positively correlated with the volume of primary lesions (r = 0.752) and also positively correlated with the quantitative values of ACE2 immunohistochemical analysis (r = 0.991). Conclusively, [<sup>99m</sup>Tc]Tc-cyc-DX600 SPECT is an ACE2-specific imaging protocol with clinical translational potential, adding multidimensional information on the disease progression of pancreatic cancer.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":"14 2","pages":"122-133"},"PeriodicalIF":2.0000,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087297/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of nuclear medicine and molecular imaging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.62347/VFHT4078","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0

Abstract

As a regulator in renin-angiotensin-aldosterone system, angiotensin-converting enzyme 2 (ACE2) closely correlated with tumor progression of pancreatic cancer, meantime, was easily affected by a variety of factors. [99mTc]Tc-cyc-DX600 SPECT was established as an ACE2-specific imaging protocol to figure out the ACE2 status in pancreatic tumor. BALB/C-NU mice were used to prepare the subcutaneous cell derived xenograft (CDX) models with HEK-293T or HEK-293T/hACE2 cells to validate ACE2 specificity of [99mTc]Tc-cyc-DX600 SPECT and establish SPECT imaging protocol. On the basis of [99mTc]Tc-cyc-DX600 SPECT and [18F]F-FDG PET/CT, ACE2-dependence on tumor size and tumor metabolism were further verified on orthotopic pancreatic cancer model with KPC cells. Immunohistochemical analysis was used to demonstrate the findings on ACE2 SPECT. [99mTc]Tc-cyc-DX600 was of superior tumor uptake in HEK-293T/hACE2 CDX than wild type (6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL at 1.5 h post injection (p.i.); 3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL at 4.5 h p.i.). For the CDX models with PANC-1 cells, a significant negative correlation between the slope of tumor volume and tumor uptake was observed (r = -0.382 for the 1-4th day; r = -0.146 for the 1-5th day; r = -0.114 for the 1-6th day; r = -0.152 for the 1-7th day; but P > 0.05 for all). For orthotopic pancreatic cancer model, the linear correlation between FDG PET and ACE2 SPECT of the pancreatic lesions was negative (r = -0.878), the quantitative values of ACE2 SPCET was positively correlated with the volume of primary lesions (r = 0.752) and also positively correlated with the quantitative values of ACE2 immunohistochemical analysis (r = 0.991). Conclusively, [99mTc]Tc-cyc-DX600 SPECT is an ACE2-specific imaging protocol with clinical translational potential, adding multidimensional information on the disease progression of pancreatic cancer.

将[99mTc]Tc标记的cyc-DX600-HYNIC作为SPECT探针,用于ACE2特异性胰腺癌成像。
作为肾素-血管紧张素-醛固酮系统的调节因子,血管紧张素转换酶2(ACE2)与胰腺癌的肿瘤进展密切相关,同时也容易受到多种因素的影响。[99mTc]Tc-cyc-DX600 SPECT是一种血管紧张素转换酶2特异性成像方案,用于了解胰腺肿瘤中血管紧张素转换酶2的状态。为了验证[99mTc]锝-cyc-DX600 SPECT的ACE2特异性并建立SPECT成像方案,研究人员利用HEK-293T或HEK-293T/hACE2细胞制备了BALB/C-NU小鼠皮下细胞衍生异种移植(CDX)模型。在[99mTc]Tc-cyc-DX600 SPECT和[18F]F-FDG PET/CT的基础上,在KPC细胞的正位胰腺癌模型上进一步验证了ACE2对肿瘤大小和肿瘤代谢的依赖性。免疫组化分析用于证明 ACE2 SPECT 的结果。HEK-293T/hACE2 CDX的[99mTc]Tc-cyc-DX600肿瘤摄取率高于野生型(注射后1.5小时,6.74 ± 0.31 %ID/mL vs 1.83 ± 0.26 %ID/mL;注射后4.5小时,3.14 ± 0.31 %ID/mL vs 1.16 ± 0.15 %ID/mL)。在使用 PANC-1 细胞的 CDX 模型中,观察到肿瘤体积斜率与肿瘤摄取量之间存在显著的负相关(第 1-4 天为 r =-0.382;第 1-5 天为 r =-0.146;第 1-6 天为 r =-0.114;第 1-7 天为 r =-0.152;但 P 均大于 0.05)。在正位胰腺癌模型中,胰腺病灶的FDG PET和ACE2 SPECT的线性相关为负值(r = -0.878),ACE2 SPCET的定量值与原发病灶的体积呈正相关(r = 0.752),与ACE2免疫组化分析的定量值也呈正相关(r = 0.991)。总之,[99mTc]Tc-cyc-DX600 SPECT是一种具有临床转化潜力的ACE2特异性成像方案,可增加胰腺癌疾病进展的多维信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信