Journal article
In vivo Evaluation of PEGylated 64Cu-liposomes with Theranostic and Radiotherapeutic Potential using Micro PET/CT
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
Department of Chemistry, Technical University of Denmark4
University of Copenhagen5
Center for Nuclear Technologies, Technical University of Denmark6
The Hevesy Laboratory, Center for Nuclear Technologies, Technical University of Denmark7
The objective of this study was to evaluate the potentialof PEGylated 64Cu-liposomes in clinical diagnosticpositron emission tomography (PET) imaging andPEGylated 177Lu-liposomes in internal tumor radiotherapythrough in vivo characterization and dosimetric analysis in ahuman xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterizedwith respect to size, charge, and 64Cu- and 177Lu-loadingefficiency.
The tumor imaging potential of 64Cu-loadedliposomes was evaluated in terms of in vivo biodistribution,tumor accumulation and tumor-to-muscle (T/M) ratios, usingPET imaging. The potential of PEGylated liposomes for diagnosticand therapeutic applications was further evaluatedthrough dosimetry analysis using OLINDA/EXM software.The 64Cu-liposomes were used as biological surrogates toestimate the organ and tumor kinetics of 177Lu-liposomes.High remote loading efficiency (>95 %) was obtainedfor both 64Cu and 177Lu radionuclides with PEGylated liposomes,and essentially no leakage of the encapsulated radionuclidewas observed upon storage and after serum incubationfor 24 h at 37 °C.
The 10 mol% PEG liposomes showedhigher tumor accumulation (6.2±0.2 %ID/g) than the 5mol% PEG liposomes, as evaluated by PET imaging. Thedosimetry analysis of the 64Cu-liposomes estimated an acceptabletotal effective dose of 3.3·10−2 mSv/MBq for diagnosticimaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177Luliposomes.
The overall preclinical profile of PEGylated64Cu-liposomes showed high potential as a new PETtheranostic tracer for imaging in humans. Dosimetry resultspredicted that initial administered activity of 200 MBq of64Cu-liposomes should be acceptable in patients. Work is inprogress to validate the utility of PEGylated 64Cu-liposomesin a clinical research programme.
The high absorbed tumordose (114 mGy/MBq) estimated for 177Lu-liposomes and thepreliminary dosimetric studies justify further therapeutic anddosimetry investigation of 177Lu-liposomes in animals beforepotential testing in man.
| Language: | English |
|---|---|
| Publisher: | Springer Berlin Heidelberg |
| Year: | 2016 |
| Pages: | 941-952 |
| ISSN: | 16197089 and 16197070 |
| Types: | Journal article |
| DOI: | 10.1007/s00259-015-3272-6 |
| ORCIDs: | Henriksen, Jonas Rosager , Elema, Dennis Ringkjøbing , Andresen, Thomas Lars and 0000-0002-2706-5547 |
Cancer imaging Diagnostic Nanoparticle PET Radiotherapy SDG 3 - Good Health and Well-being Theranostic
Animals Cardiology Cell Line, Tumor Copper Radioisotopes Humans Imaging / Radiology Journal Article Liposomes Lutetium Medicine & Public Health Mice Mice, Nude Neuroendocrine Tumors Nuclear Medicine Oncology Orthopedics Polyethylene Glycols Positron Emission Tomography Computed Tomography Radiopharmaceuticals Research Support, Non-U.S. Gov't SC11 Tissue Distribution
