Treatment of malignant brain tumors with chloroethylnitrosoureas (CENUs) in addition to surgical resection andradiotherapy remains the foundation of glioma therapy. However, the clinical response to CENUs is at best modest.A novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), as compared tothe standard CENU, 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU), has been demonstrated to have increased anticancereffects both in vitro and in vivo. Unfortunately, many human tumors have been known to be resistant toCENUs since they express DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In order toassess whether SarCNU has an effect on MGMT positive tumors, we evaluated its antitumor efficacy using anMGMT positive human glioma (SF-767) nude mouse xenograft model. Since SF-767 has high MGMT levels,BCNU treatment (20mg/kg, Q4D 3 i.p.) alone did not result in a satisfactory anticancer effect (p>0:05). Asexpected, O6-benzylguanine (O6-BG) (100mg/kg), which was given prior to BCNU treatment, by depletingMGMTactivity, significantly enhanced BCNU antitumor efficacy (p<0:001). Moreover, SarCNU treatment (167mg/kg,Q4D 3 i.p.) alone had a better antitumor effect than O6-BG plus BCNU treatment (FD 51:7, pD 0:0004). However,in this xenograft model, O6-BG did not significantly enhance the anticancer efficacy of SarCNU (FD 0:8, pD 0:411). The SF-767 human glioma xenograft is positive for extraneuronal monoamine transporter EMT (EMT)as determined by reverse-transcription polymerase chain reaction (RT-PCR). Our present results suggest that Sar-CNU is also effective for MGMT positive tumor if they exhibit EMT.