Targeted fluorescence imaging using bevacizumab‐800CW within neovascular age‐related macular degeneration (AMD) patients to evaluate the upregulation of vascular endothelial growth factor (VEGF‐A) (preliminary results)

Abstract

Aims/Purpose: With this phase 1 study, we aim to gain insight into the feasibility of using bevacizumab‐800CW to visualize the upregulation of VEGF‐A in AMD patients for treatment optimization.Methods: First, six wet AMD patients who are currently undergoing treatment with anti‐VEGF agents were included to evaluate the optimal tracer dose and received either 4.5 or 15 mg bevacizumab‐800CW. For the ongoing analysis of targeted tracer accumulation, three additional on‐therapy and three naïve patients will be included with the optimal dose of 15 mg. Fluorescence images (Heidelberg Spectralis) were taken before, up to 60 min and 3–4 days after intravenous injection of bevacizumab‐800CW. The target‐to‐background ratios (TBR) were calculated and compared between dose groups to evaluate the optimal dose. To investigate targeted tracer uptake, images of different time points are normalized and aligned, and a fluorescence intensity line is plotted over the active lesion to locate interesting areas for further quantification.Results: The preliminary results showed a clear inflow of the tracer into the eye vasculature after administration of 15 mg bevacizumab‐800CW. The fluorescence remains visible up to 1 h after tracer administration. Visual image comparison and TBR calculation in the first six patients showed that 15 mg bevacizumab‐800CW was the optimal tracer dose. In patients who received 15 mg bevacizumab‐800CW, accumulation of fluorescence signal in a smaller area within the active lesion was seen after 3–4 days.Conclusions: For the first time, we show that bevacizumab‐800CW (4.5 mg/15 mg) can be imaged in AMD patients using a commercially available system. An increase in signal intensity 3–4 days after bevacizumab‐800CW injection predicts tracer accumulation in the diseased area indicating ongoing active disease. VEGF‐A imaging can act as a proof of concept and pave the way for a broad application to track the performance of drugs by fluorescence molecular imaging.