We previously observed the enhanced anticancer efficacy of anticancer drugs encapsulated in
Ala-Pro-Arg-Pro-Gly-polyethyleneglycol-modified
liposome (APRPG-PEG-Lip) in
tumor-bearing mice, since
APRPG peptide was used as an active targeting tool to angiogenic endothelium. This modality, antineovascular
therapy (ANET), aims to eradicate
tumor cells indirectly through damaging angiogenic vessels. In the present study, we examined the in vivo trafficking of APRPG-PEG-Lip labeled with [2-(18)F]
2-fluoro-2-deoxy-D-glucose ([2-(18)F]FDG) by use of positron emission tomography (PET), and observed that the trafficking of this
liposome was quite similar to that of non-targeted long-circulating
liposome (PEG-Lip). Then, histochemical analysis of intratumoral distribution of both
liposomes was performed by use of fluorescence-labeled
liposomes. In contrast to in vivo trafficking, intratumoral distribution of both types of
liposomes was quite different: APRPG-PEG-Lip was colocalized with angiogenic endothelial cells that were immunohistochemically stained for CD31, although PEG-Lip was localized around the angiogenic vessels. These results strongly suggest that intratumoral distribution of
drug carrier is much more important for therapeutic efficacy than the total accumulation of the anticancer
drug in the
tumor, and that active delivery of anticancer drugs to angiogenic vessels is useful for
cancer treatment.