Evalution of the EPR effect in dogs with spontaneous tumors and its implications on nanotherapies

Nanoparticles are well established as effective drug delivery systems and have potential in biomedical imaging as a diagnostic tool. We have recently developed a highly efficient method for utilizing liposomes as agents in positron emission tomography (PET) imaging giving high resolution images and allowing direct quantification of liposome tissue distribution and blood clearance. Our approach is based on remote loading of a copper-radionuclide (64Cu) into preformed liposomes and copper entrapment by an encapsulated copper-chelator. We show that the 64Cu-liposomes provide quantitative in vivo imaging in canines with spontaneous tumors using PET. Seven canines with spontaneous tumors were included in the study where the main focus was to evaluate the EPR effect in large animals with spontaneous tumors and the performance of the developed liposome imaging agent. None of the included dogs displayed any anaphylactic, toxic or adverse reactions. Liposome circulating half-life ranged from 24.2 hours to 54.2 hours, with a mean half-life of 35.0 ± 4.24 hours. The study showed that the EPR effect assures substantial tumor accumulation in some but not all spontaneous tumors in canines. The included carcinomas displayed higher mean and maximum uptake levels of liposomes relative to the included sarcomas. The 64Cu-liposomes have potential as a diagnostic tracer in cancer diagnostics. We envision that the 64Cu-liposomes will be an important tool for evaluating liposome performance in future and may become an important tool in selection of cancer patients for nanoparticle based chemotherapy.

References:

Petersen AL, Binderup T, Jølck RI, Rasmussen P, Henriksen JR, Pfeifer AK, Kjær A, Andresen TL. Positron emission tomography evaluation of somatostatin receptor targeted (64)Cu-TATE-liposomes in a human neuroendocrine carcinoma mouse model. J. Control. Release 2012, 160, 254–263.

Petersen AL, Binderup T,Rasmussen P, Henriksen JR, Elema DR,Kjær A, Andresen TL, 64Cu loaded liposomes as positron emission tomography imaging agents, Biomaterials, 2011, 32(9), 2334-2341.