In vivo trafficking of liposomes labeled by novel [18F]-lipid probes

An industrial PhD project in cooperation with LiPlasome Pharma A/S focusing on radioactive labeling of liposomal drug delivery systems (DDS) in order to elucidate their in vivo behavior. Liposomes for anti-cancer therapy are meant to passively target the tumor site where selective release of the encapsulated chemotherapeutics will take place.

In order to assess the targeting and general pharmacokinetics of the DDS, synthetic 18F-labeled lipid markers will be prepared. These markers will be prepared at the Hevesy Laboratory (Risø) and labeled using fully automated synthesis techniques. Incorporation of such markers into the phospholipid bilayer of liposomes will allow for their in vivo tracking using positron emission tomography (PET). The advantage of this technique is that it is non-invasive and makes the study of real-time kinetics possible. Different markers will be prepared in order to assess lipid exchange with biological membranes and consequently the feasibility of each marker. Studies will be performed in mice and rats at the Copenhagen University Hospital (Rigshospitalet). The results will be compared to conventional kinetics studies employing 3H-labeled liposomes and 14C-labeled drugs. The activity of these isotopes in the individual isolated organs of mice will be determined by liquid scintillation.

A second part of the project will focus on the study of drug release kinetics in vivo. The liposomes developed at LiPlasome Pharma A/S are selectively degraded by phospholipases secreted by certain types of tumor cells, thereby releasing encapsulated drug. In order to study this release, radioactively labeled cargo compounds will be prepared and encapsulated in the liposomes. These will likewise by tracked using PET.

 

Contact

Andreas Tue Ingemann Jensen
Senior Researcher
DTU Nutech
+45 46 77 53 62
http://www.nutech.dtu.dk/english/research/medical-isotopes/in-vivo-trafficking-of-liposomes-labeled-by-novel-18f-lipid-probes
18 DECEMBER 2018