RT Journal Article
SR Electronic
T1 Investigation of Factors Determining the Enhanced Permeability and Retention Effect in Subcutaneous Xenografts
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 601
OP 607
DO 10.2967/jnumed.115.166173
VO 57
IS 4
A1 Michiel Bolkestein
A1 Erik de Blois
A1 Stuart J. Koelewijn
A1 Alexander M.M. Eggermont
A1 Frank Grosveld
A1 Marion de Jong
A1 Gerben A. Koning
YR 2016
UL http://jnm.snmjournals.org/content/57/4/601.abstract
AB Liposomal chemotherapy offers several advantages over conventional therapies, including high intratumoral drug delivery, reduced side effects, prolonged circulation time, and the possibility to dose higher. The efficient delivery of liposomal chemotherapeutics relies, however, on the enhanced permeability and retention (EPR) effect, which refers to the ability of macromolecules to extravasate leaky tumor vessels and accumulate in the tumor tissue. Using a panel of human xenograft tumors, we evaluated the influence of the EPR effect on liposomal distribution in vivo by injection of pegylated liposomes radiolabeled with 111In. Liposomal accumulation in tumors and organs was followed over time by SPECT/CT imaging. We observed that fast-growing xenografts, which may be less representative of tumor development in patients, showed higher liposomal accumulation than slow-growing xenografts. Additionally, several other parameters known to influence the EPR effect were evaluated, such as blood and lymphatic vessel density, intratumoral hypoxia, and the presence of infiltrating macrophages. The investigation of various parameters showed a few correlations. Although hypoxia, proliferation, and macrophage presence were associated with tumor growth, no hard conclusions or predictions could be made regarding the EPR effect or liposomal uptake. However, liposomal uptake was significantly correlated with tumor growth, with fast-growing tumors showing a higher uptake, although no biological determinants could be elucidated to explain this correlation.