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- Title
In vivo evaluation of PEGylated Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT.
- Authors
Petersen, Anncatrine; Henriksen, Jonas; Binderup, Tina; Elema, Dennis; Rasmussen, Palle; Hag, Anne; Kjær, Andreas; Andresen, Thomas
- Abstract
Purpose: The objective of this study was to evaluate the potential of PEGylated Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model. Methods: Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and Cu- and Lu-loading efficiency. The tumor imaging potential of Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of Lu-liposomes. Results: High remote loading efficiency (>95 %) was obtained for both Cu and Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 °C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the Cu-liposomes estimated an acceptable total effective dose of 3.3·10 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic Lu-liposomes. Conclusion: The overall preclinical profile of PEGylated Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of Lu-liposomes in animals before potential testing in man.
- Subjects
NANOPARTICLES; COMPANION diagnostics; POSITRON emission tomography; CANCER radiotherapy research; IMAGING of cancer; THERAPEUTICS
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2016, Vol 43, Issue 5, p941
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-015-3272-6