To assess the effect of ionizing radiation combined with a MMP inhibitor on tumor angiogenesis, we prospectively and dynamically evaluated neovessels with Doppler ultrasonography on s.c. melanomas in four treatment groups: (a) Control group (no irradiation, sterile PBS injections; top panel); (b) Radiation alone group (locally irradiated at a dose of 2x12.5 Gy; bottom left panel); (c) Drug alone group (continuous treatment with Metastat 5 days at 2.5 µg/kg/d; middle panel); and (d) Combined treatment group (concomitant ionizing radiation plus Metastat scheduling: Metastat 5 days at 2.5 µg/kg/d started 24 hours before 2x12.5 Gy ionizing radiation; bottom right panel). In these experiments, ionizing radiation antiangiogenic effects were enhanced by the simultaneous administration of Metastat; this observation correlates well with the tumor growth inhibition. Combining a MMP inhibitor with ionizing radiation in this model provided in vivo evidence of antitumor efficacy through targeting of ionizing radiation-induced invasion and angiogenesis and suggests the possible use of Metastat with radiation therapy in early clinical trials. For details, see 1717in this issue.