Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

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

doi:10.1007/s00259-020-04766-2

Abstract

PurposeAngiogenesis 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).MethodsTen 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.Results68Ga-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.Conclusions68Ga-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 registrationhttps://eudract.ema.europa.eu no. 2015-000917-31

Highlights

Head and neck squamous cell carcinomas of the mucosal surfaces (HNSCC) are the most common type of all head and neck cancers, with approximately 890,000 new cases in 2018 worldwide [1]
We investigated the in vivo biodistribution and kinetics of 68Ga-radiotracers containing the arginine-glycine-aspartic acid (RGD) in patients with primary squamous cell carcinomas of the oral cavity prior to resection and correlated these findings with histopathology
The 68Ga-RGD positron emission tomography/ computed tomography (PET/CT) images revealed variable targeting in all primary tumours

Summary

Introduction

Head and neck squamous cell carcinomas of the mucosal surfaces (HNSCC) are the most common type of all head and neck cancers, with approximately 890,000 new cases in 2018 worldwide [1]. In oral squamous cell carcinomas (OSCC), surgery with on indication followed by (chemo)radiotherapy is the first choice of treatment, whereas in most other sites in the head and neck region, (chemo)radiation is the first choice. For locally advanced and recurrent diseases, several advances to treat them with molecular targeted therapies have been made [4]. Despite these advances, treatment is often not effective in many patients, while still causing significant toxicity. Treatment is often not effective in many patients, while still causing significant toxicity This illustrates the importance of identifying predictive biomarkers to stratify patients who are most likely to benefit from (molecular) targeted therapies. A better understanding of the tumour microenvironment and its effect on treatment resistance could further improve the management of HNSCC

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