Clinical molecular imaging of VEGF-A

A potential target to be used to identify PitNET tissue is vascular endothelial growth factor A (VEGF-A). VEGF-A is a potent, endothelial-cell specific activator of angiogenesis and its expression is known to be significantly higher in PitNETs with CS invasion.¹²

Bevacizumab binds and neutralises all isoforms of human VEGF-A. VEGF-A is endothelial cell-specific and is one of the key regulators of angiogenesis in general, including the promotion of tumour progression and metastasis.¹³ In PitNETs, it is known to correlate with disease progression and haemorrhage.^{14 15} Overexpression of VEGF has been observed in lactotroph PitNETs, especially in men, and in pituitary carcinomas.^16–19 Bevacizumab can be labelled (ratio 1:2) with the NIR organic fluorophore IRDye800CW, developed by LI-COR Biosciences (Lincoln, Nebraska, USA) and can be used for NIR imaging. Labelling of bevacizumab to IRDye800CW is performed at the Department of Clinical Pharmacy and Pharmacology of the University Medical Centre Groningen under Good Manufacturing Practice (GMP) conditions. Therefore, it is expected that the tracer bevacizumab-800CW accumulates in the pituitary microenvironment. The aim of this study is to visualise the fluorescence in the NIR spectrum using the fluorescence endoscopy system during pituitary surgery. In addition, this technique may be able to differentiate the poorly vascularised microcorticotroph tumour from the well vascularised normal surrounding pituitary.