Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [ 68 Ga]Ga-DOTA-E-[c(RGDfK)] 2 PET/CT
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ORIGINAL ARTICLE
Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT D. Lobeek 1 & M. Rijpkema 1 & S. Y. A. Terry 2 & J. D. M. Molkenboer-Kuenen 1 & L. Joosten 1 & E. A. J. van Genugten 1,3 & A. C. H. van Engen-van Grunsven 4 & J. H. A. M. Kaanders 5 & S. A. H. Pegge 1 & O. C. Boerman 1 & W. L. J. Weijs 6 & M. A. W. Merkx 6 & C. M. L. van Herpen 7 & R. P. Takes 8 & E. H. J. G. Aarntzen 1 & W. J. G. Oyen 1,9,10 Received: 17 December 2019 / Accepted: 10 March 2020 # The Author(s) 2020
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 αvβ3 integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we validated the feasibility of 68Ga[Ga]DOTA-E-[c(RGDfK)]2 (68Ga-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 68Ga-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 αvβ3 integrin to assess the expression pattern. Results 68Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUVmax 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 68Ga-RGD PET/CT of αvβ3 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 Keywords RGD-PET/CT . Angiogenesis . Squamous cell carcinoma . Head and neck cancer . αvβ3 integrin This article is part of the Topical Collection on Oncology - Head and Neck Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-020-04766-2) contains supplementary material, which is available to authorized users. * D. Lobeek [email protected] 1
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
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Department of Radiotherapy, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands
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Department of Oral and Maxillofacial Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
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Department
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