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

Abstract

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 α_vβ₃ 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). 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 α_vβ₃ integrin to assess the expression pattern. ⁶⁸Ga-RGD tumour accumulation was observed in all patients. At 60 min post injection, tumour SUV_max 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. ⁶⁸Ga-RGD PET/CT of α_vβ₃ 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. https://eudract.ema.europa.eu no. 2015-000917-31.