Imaging of tumor vascularization using fluorescence molecular tomography to monitor arginine deiminase treatment in melanoma.
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.
Department of Nuclear Medicine, Human Oncology and Pathogenesis Program, and Ludwig Institute for Cancer Research, New York Branch, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. lars.stelter@charite.de
Lars
L
Stelter
Michael J
MJ
Evans
Achim A
AA
Jungbluth
Valerie A
VA
Longo
Pat
P
Zanzonico
Gerd
G
Ritter
John S
JS
Bomalaski
Lloyd
L
Old
Steven M
SM
Larson
D000818:Animals; D001124:Argininosuccinate Synthase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology*; D007150:Immunohistochemistry; D008545:Melanoma / Q000098:blood supply* / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D061848:Optical Imaging / Q000379:methods*; D014054:Tomography / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D009569:Nitric Oxide; D006867:Hydrolases; C019723:arginine deiminase; D001124:Argininosuccinate Synthase