Based on their inability to express
argininosuccinate synthetase (ASS), some
cancer entities feature the characteristic of
L-arginine (Arg) auxotrophy. This inability to intrinsically generate Arg makes them applicable for
arginine deiminase (ADI) treatment, an Arg-depleting
drug. Arg is also used for the synthesis of endothelial
nitric oxide (NO), which mainly confers vasodilatation but is also considered to have a major influence on
tumor vascularization. The purpose of this study was to define changes in
tumor vasculature in an ADI-treated
melanoma xenograft mouse model using the blood pool agent AngioSense 750 and fluorescence molecular tomography (FMT). We used an ASS-negative
melanoma xenograft mouse model and subjected it to weekly ADI treatment. Changes in
tumor size were measured, and alterations in
tumor vasculature were depicted by FMT and CD31 immunohistochemistry (IHC). On ADI treatment and effective antitumor
therapy, we observed a drop in NO plasma levels and visualized changes in
tumor vascularization with FMT and IHC. ADI treatment in
melanoma xenografts has a
tumor-reducing effect, which can be noninvasively imaged by quantifying
tumor vascularization with FMT and IHC.