Folate receptor targeting of radiolabeled liposomes reduces intratumoral liposome accumulation in human KB carcinoma xenografts

Abstract

Esben Christensen,1–3 Jonas R Henriksen,2,4 Jesper T Jørgensen,3 Yasmine Amitay,5 Hilary Shmeeda,5 Alberto A Gabizon,5 Andreas Kjær,3 Thomas L Andresen,1,2 Anders E Hansen1–3 1Department of Micro- and Nanotechnology, DTU Nanotech, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; 2Center for Nanomedicine and Theranostics, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; 3Cluster for Molecular Imaging, Department of Biomedical Sciences and Department of Clinical Physiology, Nuclear Medicine & PET, University of Copenhagen and Rigshospitalet, DK-2200 & DK-2100, Copenhagen, Denmark; 4Department of Chemistry, DTU Chemistry, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark; 5Shaare Zedek Medical Center and Hebrew University – School of Medicine, Jerusalem, Israel Background: Active, ligand-mediated, targeting of functionalized liposomes to folate receptors (FRs) overexpressed on cancer cells could potentially improve drug delivery and specificity. Studies on folate-targeting liposomes (FTLs) have, however, yielded varying results and generally fail to display a clear benefit of FR targeting.Method: Tumor accumulating potential of FTLs and NTLs were investigated in a FR overexpressing xenograft model by positron emission tomography/computed tomography imaging.Results: Tumors displayed significantly lower activity of FTLs than NTLs. Furthermore, FTLs displayed worse circulating properties and increased liver-accumulation than NTLs. Conclusion: This study underlines that long-circulating properties of liposomes must be achieved to take advantage of EPR-dependent tumor accumulation which may be lost by functionalization. FR-functionalization negatively affected both tumor accumulation and circulation properties. Keywords: liposomes, folate, cancer, imaging, PET, EPR

Keywords

• Liposomes
• Folate
• Cancer
• Imaging
• PET