Figure 3.

Effect of depletion of extracellular matrix components on liposomal doxorubicin intratumoral distribution and penetration. Autoradiographs of tumors receiving intravenous collagenase-2 (A), intratumoral deactivated collagenase-2 (B) or intratumoral active collagenase-2 (C) and collected 24 hours after intravenous injection of ^99mTc-liposomal doxorubicin. Microscopic examination of collagen from tumor sections receiving intravenous collagenase-2 (D), intratumoral deactivated collagenase-2 (E) or intratumoral active collagenase-2 (F) and liposomal doxorubicin distribution in tumor sections from rats pretreated with intravenous collagenase-2 (G), intratumoral deactivated collagenase-2 (H) or intratumoral active collagenase-2 (I). Gamma camera images of rats bearing two head and neck tumors at the nape of the neck pretreated with intravenous collagenase-2 and intravenously injected with ^99mTc-liposomal doxorubicin to monitor the tumor accumulation of ^99mTc-liposomal doxorubicin at 1 h (J) or 24 h (K) post-injection. Images of tumor-bearing rats pretreated with intratumoral collagenase-2 and intravenously injected with ^99mTc-liposomal doxorubicin to monitor tumor accumulation at 1 h (L) or 20 h (M). Reproduced with permission from [58]. Fluorescent microscopic images of doxorubicin distribution collected from tumors excised from mice intravenously injected with liposomal doxorubicin without (N) or with (O) hyaluronidase pretreatment. Reproduced with permission from [60].