Long-term effect of intravenous and subcutaneous application of tTF-NGR on the growth of fibrosarcoma (HT1080) xenotransplants in mice. (A) Growth inhibition of HT1080 by subcutaneous administration of tTF-NGR (1 mg/kg bw [♦], n = 7, or 3 mg/kg bw [■], n = 7, respectively) compared with saline ([•], n = 6). Arrows indicate the time points of injection (2 applications). Data are presented as means ± SE. (B) Tumor shrinkage and growth inhibition of HT1080 by subcutaneous administration of tTF-NGR (3 mg/kg bw [■], n = 7, or 5 mg/kg bw [▴], n = 7, respectively) compared with the intravenous administration of tTF-NGR (1 mg/kg bw [♦], n = 6) or saline ([•], n = 7). Arrows indicate the time points of injection (4 applications). Data are presented as means with SE. * denotes first day of statistical significance between tTF-NGR and saline (Mann-Whitney rank-sum test for independent groups; P < .05 were considered significant). At day 32, the control cohort was removed because of tumor size or spontaneous ulceration. CR, complete remission. (C) Re-exposition of prior tTF-NGR–treated (after regrowth, ▴) in comparison to previously untreated tumor-bearing animals (■). Growth of HT1080 was inhibited by subcutaneous administration of tTF-NGR (3 mg/kg bw, each group with n = 4). Arrows indicate the time points of injection. Data are presented as means ± SE. There were no significant differences between both groups.