Scientigraphic images of rats treated without hyperthermia (A) or with local HT (B) 18 hours after injection of radiolabeled liposomes. Increased intratumoral accumulation of liposomes can be seen following HT. Intratumoral doxorubicin concentration 18 hours postinjection as a function of uptake of a 99mTc liposomal tracer (C). Adapted and reprinted with permission from 11. The results for HPLC validated [DOX] measurements (D), fluorescence validated [DOX] measurements (E), and an overlay of both experiments (F) from individual animals. Adapted and reprinted with permission from 35. Tumor drug distribution after administration of DOX- and Mn-containing thermosensitive liposomes and HT with 3 different schedules. Thermosensitive liposomes administered during steady-state HT result in peripheral enhancement (G); thermosensitive liposomes administered before HT result in central enhancement (H); thermosensitive liposomes administered in split doses (half before HT and half during steady-state HT) result in uniform concentrations (I). Liposome content release shows white. Adapted and reprinted with permission from 36. Tumor doxorubicin concentration and antitumor effect for therapeutic protocols described in Figures 2G-I. Overall tumor doxorubicin concentration (ng/mg) as measured by HPLC (J); rat fibrosarcoma growth time for each group (n = 6,7) measured as median days to five times the original tumor volume (K); Kaplan-Meier plot showing cumulative fraction of animals with tumor volume less than five times the treatment volume for each group over time (L). In all panels, gray = control groups (control, HT alone, free Dox, free Dox + HT, Dox/Mn-LTSL alone); blue = Dox/Mn-LTSL before HT; red = Dox/Mn-LTSL during HT; green = Dox/Mn-LTSL split dose. Adapted and reprinted with permission from 36.