Journal article
Positron emission tomography evaluation of somatostatin receptor targeted (64)Cu-TATE-liposomes in a human neuroendocrine carcinoma mouse model
Department of Micro- and Nanotechnology, Technical University of Denmark1
Colloids and Biological Interfaces, Department of Micro- and Nanotechnology, Technical University of Denmark2
Center for Nanomedicine and Theranostics, Centers, Technical University of Denmark3
University of Copenhagen4
The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark5
Center for Nuclear Technologies, Technical University of Denmark6
Physical and Biophysical Chemistry, Department of Chemistry, Technical University of Denmark7
Copenhagen University Hospital Herlev and Gentofte8
Targeted therapeutic and diagnostic nanocarriers functionalized with antibodies, peptides or other targeting ligands that recognize over-expressed receptors or antigens on tumor cells have potential in the diagnosis and therapy of cancer. Somatostatin receptors (SSTRs) are over-expressed in a variety of cancers, particularly neuroendocrine tumors (NETs) and can be targeted with somatostatin peptide analogs such as octreotate (TATE).
In the present study we investigate liposomes that target SSTR in a NET xenograft mouse model (NCI-H727) by use of TATE. TATE was covalently attached to the distal end of DSPE-PEG(2000) on PEGylated liposomes with an encapsulated positron emitter (64)Cu that can be utilized for positron emission tomography (PET) imaging.
The biodistribution and pharmacokinetics of the (64)Cu-loaded PEGylated liposomes with and without TATE was investigated and their ability to image NETs was evaluated using PET. Additionally, the liposome accumulation and imaging capability was compared with free radiolabelled TATE peptide administered as (64)Cu-DOTA-TATE.
The presence of TATE on the liposomes resulted in a significantly faster initial blood clearance in comparison to control-liposomes without TATE. PEGylated liposomes with or without TATE accumulated at significantly higher quantities in NETs (5.1±0.3 and 5.8±0.2 %ID/g, respectively) than the free peptide (64)Cu-DOTA-TATE (1.4±0.3 %ID/g) 24h post-injection.
Importantly, (64)Cu-loaded PEGylated liposomes with TATE showed significantly higher tumor-to-muscle (T/M) ratio (12.7±1.0) than the control-liposomes without TATE (8.9±0.9) and the (64)Cu-DOTA-TATE free peptide (7.2±0.3). The higher T/M ratio of the PEGylated liposomes with TATE suggests some advantage of active targeting of NETs, although no absolute benefit in tumor accumulation over the non-targeted liposomes was observed.
Collectively, these data showed that (64)Cu-loaded PEGylated liposomes with TATE conjugated to the surface could be promising new imaging agents for visualizing tumor tissue and especially NETs using PET.
| Language: | English |
|---|---|
| Year: | 2012 |
| Pages: | 254-263 |
| ISSN: | 18734995 and 01683659 |
| Types: | Journal article |
| DOI: | 10.1016/j.jconrel.2011.12.038 |
| ORCIDs: | 0000-0002-2706-5547 , Henriksen, Jonas Rosager and Andresen, Thomas Lars |
Liposomes Nanoparticles Octreotate Positron emission tomography SDG 3 - Good Health and Well-being Somatostatin Targeting ligand
1,2-distearoylglycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000)octreotate 64Cu-DOTATATE Animals Carcinoma, Neuroendocrine Cell Line, Tumor Copper Radioisotopes Female Humans Isotope Labeling Mice Mice, Nude Molecular Structure Octreotide Organometallic Compounds Phosphatidylethanolamines Positron-Emission Tomography Radiopharmaceuticals Real-Time Polymerase Chain Reaction Receptors, Somatostatin Tissue Distribution Xenograft Model Antitumor Assays
