Positron emission tomography evaluation of somatostatin receptor targeted 64Cu-TATE-liposomes in a human neuroendocrine carcinoma mouse model

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-PEG2000 on PEGylated liposomes with an encapsulated positron emitter 64Cu that can be utilized for positron emission tomography (PET) imaging. The biodistribution and pharmacokinetics of the 64Cu-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 64Cu-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 64Cu-DOTA-TATE (1.4 ± 0.3 %ID/g) 24 h post-injection. Importantly, 64Cu-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 64Cu-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 64Cu-loaded PEGylated liposomes with TATE conjugated to the surface could be promising new imaging agents for visualizing tumor tissue and especially NETs using PET.

The biodistribution of TATE-functionalized 64Cu loaded liposomes, designed for somatostatin receptor (SSTR) targeting, was investigated by positron emission tomography in a neuroendocrine tumor xenograft model and compared with non-targeted liposomes.Figure optionsDownload high-quality image (440 K)Download as PowerPoint slide