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利用[镓]Ga-DOTA-E-[c(RGDfK)] PET/CT对头颈部鳞状细胞癌患者的血管生成进行成像。

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [Ga]Ga-DOTA-E-[c(RGDfK)] PET/CT.

作者信息

Lobeek D, Rijpkema M, Terry S Y A, Molkenboer-Kuenen J D M, Joosten L, van Genugten E A J, van Engen-van Grunsven A C H, Kaanders J H A M, Pegge S A H, Boerman O C, Weijs W L J, Merkx M A W, van Herpen C M L, Takes R P, Aarntzen E H J G, Oyen W J G

机构信息

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.

Department of Imaging Chemistry and Biology, King's College London, London, UK.

出版信息

Eur J Nucl Med Mol Imaging. 2020 Oct;47(11):2647-2655. doi: 10.1007/s00259-020-04766-2. Epub 2020 Mar 20.

Abstract

PURPOSE

Angiogenesis plays an important role in the growth and metastatic spread of solid tumours and is characterised by the expression of integrins on the cell surface of endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related αβ integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we validated the feasibility of Ga[Ga]-DOTA-E-[c(RGDfK)] (Ga-RGD) PET/CT to visualise angiogenesis in patients with oral squamous cell carcinoma (OSCC).

METHODS

Ten patients with OSCC and scheduled for surgical resection including elective neck dissection received an intravenously administration of Ga-RGD (42 ± 8 μg; 214 ± 9 MBq). All patients subsequently underwent dynamic (n = 5) or static PET/CT imaging (n = 5) for 60 min or for 4 min/bed position at 30, 60 and 90 min after injection, respectively. Quantitative tracer uptake in tumour lesions was expressed as standardised uptake values (SUV). Additionally, tumour tissue was immunohistochemically stained for αβ integrin to assess the expression pattern.

RESULTS

Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUV ranged between 4.0 and 12.7. Tracer accumulation in tumour tissue plateaued at 10 min after injection. Uptake in background tissue did not change over time, resulting in tumour-to-muscle tissue of 6.4 ± 0.7 at 60 min post injection.

CONCLUSIONS

Ga-RGD PET/CT of αβ integrin expression in OSCC patients is feasible with adequate tumour-to-background ratios. It will provide more insight in angiogenesis as a hallmark of the head and neck squamous cell carcinomas' tumour microenvironment.

TRIAL REGISTRATION

https://eudract.ema.europa.eu no. 2015-000917-31.

摘要

目的

血管生成在实体瘤的生长和转移扩散中起重要作用,其特征是内皮细胞表面整合素的表达。放射性标记的RGD肽特异性靶向在新生血管的活化内皮细胞上表达的血管生成相关αβ整合素。在此,我们验证了镓[Ga]-DOTA-E-[c(RGDfK)](Ga-RGD)PET/CT在口腔鳞状细胞癌(OSCC)患者中可视化血管生成的可行性。

方法

10例计划接受手术切除(包括择期颈清扫术)的OSCC患者静脉注射Ga-RGD(42±8μg;214±9MBq)。所有患者随后分别在注射后60分钟进行动态(n = 5)或静态PET/CT成像(n = 5),或在30、60和90分钟时以每个床位4分钟进行静态PET/CT成像。肿瘤病变中的定量示踪剂摄取以标准化摄取值(SUV)表示。此外,对肿瘤组织进行αβ整合素免疫组织化学染色以评估表达模式。

结果

所有患者均观察到Ga-RGD在肿瘤中的蓄积。注射后60分钟,肿瘤SUV范围为4.0至12.7。示踪剂在肿瘤组织中的蓄积在注射后10分钟达到平台期。背景组织中的摄取随时间没有变化,注射后60分钟时肿瘤与肌肉组织的比值为6.4±0.7。

结论

OSCC患者中αβ整合素表达的Ga-RGD PET/CT在肿瘤与背景比值合适的情况下是可行的。它将为作为头颈部鳞状细胞癌肿瘤微环境标志的血管生成提供更多见解。

试验注册

https://eudract.ema.europa.eu,编号2015-000917-31。

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