TY - JOUR

T1 - Noninvasive molecular imaging of the enhanced permeability and retention effect by64Cu-liposomes

T2 - In vivo correlations with68Ga-RGD, fluid pressure, diffusivity and18F-FDG

AU - Børresen, Betina

AU - Hansen, Anders Elias

AU - Fliedner, Frederikke Petrine

AU - Henriksen, Jonas Rosager

AU - Elema, Dennis Ringkjøbing

AU - Brandt-Larsen, Malene

AU - Kristensen, Lotte Kellemann

AU - Kristensen, Annemarie Thuri

AU - Andresen, Thomas Lars

AU - Kjær, Andreas

PY - 2020

Y1 - 2020

N2 - Background: The accumulation of liposome encapsulated chemotherapy in solid cancers is dependent on the presence of the enhanced permeability and retention (EPR) effect. Positron emission tomography (PET) imaging with a liposome encapsulated radioisotope, such as liposome encapsulated Cu-64 (64Cu-liposome) may help to identify tumors with high lipo-some accumulation, and thereby stratify patients based on expected benefit from liposomal chemotherapy. However, intravenous administration of liposomes without a cytotoxic con-tent is complicated by the accelerated blood clearance (ABC) phenomenon for succeeding therapeutic liposome dosing. Alternative markers for assessing the tumor’s EPR level are therefore warranted. Materials and Methods: To increase our understanding of EPR variations and to ulti-mately identify an alternative marker for the EPR effect, we investigated the correlation between64Cu-liposome PET/CT (EPR effect) and68Ga-RGD PET/CT (neoangiogenesis),18F-FDG PET/CT (glycolysis), diffusion-weighted MRI (diffusivity) and interstitial fluid pressure in two experimental cancer models (CT26 and COLO 205). Results:64Cu-liposome and68Ga-RGD SUVmax displayed a significant moderate correla-tion, however, none of the other parameters evaluated displayed significant correlations. These results indicate that differences in neoangiogenesis may explain some EPR variability, however, as correlations were only moderate and not observed for SUVmean,68Ga-RGD is probably insufficient to serve as a stand-alone surrogate marker for quantifying the EPR effect and stratifying patients.

AB - Background: The accumulation of liposome encapsulated chemotherapy in solid cancers is dependent on the presence of the enhanced permeability and retention (EPR) effect. Positron emission tomography (PET) imaging with a liposome encapsulated radioisotope, such as liposome encapsulated Cu-64 (64Cu-liposome) may help to identify tumors with high lipo-some accumulation, and thereby stratify patients based on expected benefit from liposomal chemotherapy. However, intravenous administration of liposomes without a cytotoxic con-tent is complicated by the accelerated blood clearance (ABC) phenomenon for succeeding therapeutic liposome dosing. Alternative markers for assessing the tumor’s EPR level are therefore warranted. Materials and Methods: To increase our understanding of EPR variations and to ulti-mately identify an alternative marker for the EPR effect, we investigated the correlation between64Cu-liposome PET/CT (EPR effect) and68Ga-RGD PET/CT (neoangiogenesis),18F-FDG PET/CT (glycolysis), diffusion-weighted MRI (diffusivity) and interstitial fluid pressure in two experimental cancer models (CT26 and COLO 205). Results:64Cu-liposome and68Ga-RGD SUVmax displayed a significant moderate correla-tion, however, none of the other parameters evaluated displayed significant correlations. These results indicate that differences in neoangiogenesis may explain some EPR variability, however, as correlations were only moderate and not observed for SUVmean,68Ga-RGD is probably insufficient to serve as a stand-alone surrogate marker for quantifying the EPR effect and stratifying patients.

KW - EPR effect

KW - Liposome

KW - Neoangiogenesis

KW - Positron emission tomography

U2 - 10.2147/IJN.S239172

DO - 10.2147/IJN.S239172

M3 - Journal article

C2 - 33173294

AN - SCOPUS:85094911155

VL - 15

SP - 8571

EP - 8581

JO - International Journal of Nanomedicine

JF - International Journal of Nanomedicine

SN - 1176-9114

ER -