The ability of an inserted electrode to detect in vivo NO in tumor was achieved by using a chemically modified Pt/Ir electrode as NO-sensor and nitroglycerin NTG as NO donor. Enzymatically induced release of NO from NTG was tracked in the tumor, upon intra peritoneal injection of NTG. This approach allowed in vivo monitoring of the bioavailability of NO and could be applied to the in vivo study of candidate anticancer drugs acting on the NO pathways.Keywords: Tumor, In vivo detection, Nitric oxide, Nitroglycerin, NO-sensor, Electrochemical detection DOI: 10.1002/elan.200804300 Tumor vasculature plays an essential role in tumor survival and development, leading to the concepts of antiangiogenic and antivascular therapy [1 -3]. While the antiangiogenic strategy targets the formation of tumor new vessels, the antivascular drugs aim at targeting the existing tumoral vasculature and at causing tumor endothelial cells death [4]. One of the principal actors in the antivascular approach appears to involve the action of nitric oxide (NO) [2 -6]. Thus, it is believed that this induced NO-release could be considered, at least partially, as an in vivo marker of the anticancer activity of this class of agents. Interest in elucidating the mechanism of action of several classes of anticancer agents and also in exploring the pathways of the induced-NO release provides an impetus for conceiving a well-designed approach to locally detect NO in tumors, in vivo. Measuring NO from liquid samples is now well documented [7] and the electrochemical detection systems are recognized as being the only reliable analytical method to determine NO local concentration in real time, without disturbing its metabolism and its associated regulatory pathways [8,9].We recently extended the use of the electroanalytical concept and adapt it to a very special and complex biological tissue such as tumors [10]. We have demonstrated that miniaturized electrochemical sensor can be used in vivo for probing electroactive species in tumor-bearing mice. This was first achieved by performing for the first time in vivo cyclic voltammetry of K 4 Fe(CN) 6 . In addition, the use of two NO donors allowed, for the first time, to demonstrate the feasibility of the electrochemical detection of directly injected exogenous NO in live tumor-bearing mice.Nitroglycerin (NTG) is one of the oldest NO donors reported in the literature. It is enzymatically metabolized in living systems and the produced NTG-derived NO diffuses into the surrounding tissues [11,12]. Thus, the change in basal level of NO through induced enzymatically decomposed NTG constitutes a pertinent approach to explore our electroanalytical methodology to footpath intra tumoral NO. This led us to explore the monitoring of changes in the intra tumoral NO levels upon intra-peritoneal injection of NTG. Thus, in this work we report for the first time on the local in vivo tracking of changes in level of NTG-derived NO in tumor bearing mice in order to path the way for future studies of the evaluation of ...