Tumor perfusion imaging predicts the intra-tumoral accumulation of liposomes

The intra-tumoral relationship between microcirculation, interstitial fluid pressure and liposome accumulation

“…However, insufficient experimental evidence is available to fully delineate the relationships between tumor microcirculation, IFP, and the intra-tumoral accumulation of nanoparticles. In a recent study, we found a significant positive correlation between tumor perfusion and liposome accumulation with regional variations in perfusion giving rise to intra-tumoral heterogeneity in liposome distribution [11]. As well, we showed through mathematical modeling the critical role that IFP plays in driving intra-tumoral heterogeneity in liposome accumulation [8].…”

“…The intra-tumoral distribution of drug has been identified as a critical determinant of efficacy with inadequate distribution of drug being considered a physical mechanism of drug resistance [9,10]. High-resolution pre-clinical imaging has confirmed that the intra-tumoral distribution of liposomes is often heterogeneous throughout the tumor volume [8,11,12]. Therefore, the intra-tumoral distribution of nanoparticles may be more clinically relevant than bulk tumor accumulation in determining the success of nanomedicine-based therapy.…”

Spatial and temporal mapping of heterogeneity in liposome uptake and microvascular distribution in an orthotopic tumor xenograft model

“…Despite the limitations of 2D image analysis, such representation of tumor vascularity is supported by similar studies whereby good correlation was found between 2D and 3D measurements [11,64]. Immunohistochemical evaluation may indeed present a relatively accessible means to gauge tumor vascularity as a contributor to the EPR effect; nevertheless, such estimation would be strengthened by integration of additional parameters (e.g., perfusion status) and/or dimensions [30,64]. In the periphery of the tumor, time-and MVD-dependent accumulation was also found, while no significant change is observed in the core of the tumor over 5 days.…”

“…However, these formulations require labeling with or encapsulation of the appropriate contrast agent or probe, and they must then undergo the required evaluation of safety and toxicity. Alternately, a more straightforward approach may be to employ image-based assessment of the TME as a means to inform the microdistribution of nanomedicines [30] and/or their anti-tumor effect. Zhang et al employed a multimodality imaging approach to monitor the induction of apoptosis following administration of Doxil®.…”

“…The tumor microenvironment (TME) has indeed been implicated in the resistance of lesions to both conventional and nanoparticle-based therapy. In particular, aberrant tumor vascular structure and function, solid stress, and interstitial hypertension [27] exacerbate the heterogeneous tumor distribution of delivered therapeutics, resulting in their limited penetration and/or anti-tumor activity [28][29][30]. Variability in tumor properties has been reported across tumor types, among tumors of the same type as well as within the same tumor [31][32][33].…”