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使用与白蛋白结合域偶联的IRDye800CW-DOTA改进多模态肿瘤坏死成像。

Improved Multimodal Tumor Necrosis Imaging with IRDye800CW-DOTA Conjugated to an Albumin-Binding Domain.

作者信息

Stroet Marcus C M, de Blois Erik, de Jong Marion, Seimbille Yann, Mezzanotte Laura, Löwik Clemens W G M, Panth Kranthi M

机构信息

Erasmus MC, Department of Radiology & Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.

Erasmus MC, Department of Molecular Genetics, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.

出版信息

Cancers (Basel). 2022 Feb 9;14(4):861. doi: 10.3390/cancers14040861.

DOI:10.3390/cancers14040861
PMID:35205609
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8870237/
Abstract

PURPOSE

To assess our improved NACA for the detection of tumor necrosis.

METHODS

We increased the blood circulation time of our NACA by adding an albumin-binding domain to the molecular structure. We tested the necrosis avidity on dead or alive cultured cells and performed SPECT and fluorescence imaging of both spontaneous and treatment-induced necrosis in murine breast cancer models. We simultaneously recorded [F]FDG-PET and bioluminescence images for complementary detection of tumor viability.

RESULTS

We generated two albumin-binding IRDye800CW derivatives which were labeled with indium-111 with high radiochemical purity. Surprisingly, both albumin-binding NACAs had >10x higher in vitro binding towards dead cells. We selected [In] for in vivo experiments which showed higher dead cell binding in vitro and in vivo stability. The doxorubicin-treated tumors showed increased [In]-uptake (1.74 ± 0.08%ID/g after saline treatment, 2.25 ± 0.16%ID/g after doxorubicin treatment, = 0.044) and decreased [F]FDG-uptake (3.02 ± 0.51%ID/g after saline treatment, 1.79 ± 0.11%ID/g after doxorubicin treatment, = 0.040), indicating therapy efficacy. Moreover, we detected increased [In]uptake and tumor necrosis in more rapidly growing EMT6 tumors.

CONCLUSIONS

Our albumin-binding NACA based on IRDye800CW facilitates tumor-necrosis imaging for assessment of therapy efficacy and aggressiveness in solid tumors using both fluorescence and SPECT imaging.

摘要

目的

评估我们改进的用于检测肿瘤坏死的NACA。

方法

我们通过在分子结构中添加白蛋白结合域来延长NACA的血液循环时间。我们测试了其对死细胞或活细胞的坏死亲和力，并在小鼠乳腺癌模型中对自发和治疗诱导的坏死进行了单光子发射计算机断层扫描（SPECT）和荧光成像。我们同时记录了[F]氟代脱氧葡萄糖正电子发射断层显像（FDG-PET）和生物发光图像，以互补检测肿瘤活力。

结果

我们生成了两种白蛋白结合IRDye800CW衍生物，它们用放射性化学纯度高的铟-111进行了标记。令人惊讶的是，两种白蛋白结合的NACA对死细胞的体外结合力都高出10倍以上。我们选择[In]用于体内实验，其在体外显示出更高的死细胞结合力和体内稳定性。阿霉素治疗的肿瘤显示[In]摄取增加（盐水治疗后为1.74±0.08%注射剂量/克，阿霉素治疗后为2.25±0.16%注射剂量/克，P = 0.044），[F]FDG摄取减少（盐水治疗后为3.02±0.51%注射剂量/克，阿霉素治疗后为1.79±0.11%注射剂量/克，P = 0.040），表明治疗有效。此外，我们在生长更快的EMT6肿瘤中检测到[In]摄取增加和肿瘤坏死。

结论

我们基于IRDye800CW的白蛋白结合NACA有助于通过荧光和SPECT成像对实体瘤的治疗效果和侵袭性进行评估的肿瘤坏死成像。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/85c815be648b/cancers-14-00861-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/8ebe0f5ed0d3/cancers-14-00861-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/b78c591f4fdd/cancers-14-00861-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/a975d286a7b7/cancers-14-00861-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/fddba4fe0e13/cancers-14-00861-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/f3d43ceffd42/cancers-14-00861-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/a075ba8621a0/cancers-14-00861-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/48dab2408755/cancers-14-00861-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/85c815be648b/cancers-14-00861-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/8ebe0f5ed0d3/cancers-14-00861-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/b78c591f4fdd/cancers-14-00861-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/a975d286a7b7/cancers-14-00861-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/fddba4fe0e13/cancers-14-00861-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/f3d43ceffd42/cancers-14-00861-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/a075ba8621a0/cancers-14-00861-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/48dab2408755/cancers-14-00861-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9017/8870237/85c815be648b/cancers-14-00861-g006.jpg

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本文引用的文献

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Necrosis binding of Ac-Lys(IRDye800CW)-Tyr-octreotate: a consequence from cyanine-labeling of small molecules.
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