RCR8: Development of Radiolabelled Drug Carrier Systems for Molecularly Targeted Radiotherapy

Jyothi Menon1,Joshua Owen1,Robert Carlisle1,Katherine Vallis1

1University of Oxford, Oxford, UK

Presenting date: Tuesday 3 November
Presenting time: 13.10-14.00


Tagging of radioisotopes to targeting moieties such as peptides, antibodies and nucleotides aids in more precise delivery of these isotopes to cancer cells for treatment. However some of the obstacles to successful delivery of these radiolabelled molecules include poor circulation half-life, inefficient tumour extravasation and penetration. Liposomal and poly lactic-co-glycolic acid (PLGA) drug carrier systems have extended circulation profiles but would benefit from enhanced binding and entry into target cancer cells. To address some of these challenges, liposomes and PLGA particles tagged with radiolabelled targeting moieties were designed, formulated and then tested for specific binding to cancer cell lines.


Distearoylphosphatidylethanolamine-poly ethylene glycol (DSPE-PEG) based liposomes and PLGA particles were developed and surface modified with epidermal growth factor-diethylenetriamine pentaacetate (EGF-DTPA) followed by 111In radiolabelling. The EGF-tagged formulations were characterised using zetasizer and transmission electron microscopy (TEM). Direct particle cytotoxicity was assessed using the MTT assay. Targeting capabilities were studied by exposing EGFR+ve luciferase-expressing MDA-MB-231 or EGFR-ve luciferase expressing MCF7 breast cancer cells to EGF-tagged or non-tagged particles containing the model drug luciferin.


The particles were spherical in morphology with a diameter of 140-160 nm. More than 95% of the 111In added was tagged to the particles. Neither liposomes nor PLGA particles showed intrinsic cytotoxicity. Greater delivery (2-fold increase, p<0.05) of EGF-tagged luciferin-containing particles was observed in MDA-MB-231 cells than in MCF7 cells, this was not the case for non-tagged particles. EGF-tagged particles also gave better delivery (3.5-fold increase, p<0.05) than non-tagged particles in MDA-MB-231 cells, this was not the case in MCF7 cells.


Preliminary work on 111In- and EGF-tagged liposomes and PLGA particles have shown promise in vitro in terms of targeted cellular uptake and drug delivery. Further studies include receptor binding kinetics and feasibility of using these systems in vivo for ultrasound-assisted radiopharmaceutical delivery.