Anncatrine Luisa Petersen1,2, Jonas Rosager Henriksen2,3, Tina Binderup4, Dennis Ringkjøbing Elema2,5, Palle Hedengran Rasmussen5, Anne Mette Hag4, Andreas Kjær4, Thomas Lars Andresen6,7. 1. Department of Micro- and Nanotechnology, Technical University of Denmark, Building 345, 2800, Lyngby, Denmark. 2. Center for Nanomedicine and Theranostics, Technical University of Denmark, 2800, Lyngby, Denmark. 3. Department of Chemistry, Technical University of Denmark, Building 206, 2800, Lyngby, Denmark. 4. Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet & Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark. 5. Center for Nuclear Technologies, Hevesy Laboratory, Technical University of Denmark, Frederiksborgvej 399, 4000, Roskilde, Denmark. 6. Department of Micro- and Nanotechnology, Technical University of Denmark, Building 345, 2800, Lyngby, Denmark. thomas.andresen@nanotech.dtu.dk. 7. Center for Nanomedicine and Theranostics, Technical University of Denmark, 2800, Lyngby, Denmark. thomas.andresen@nanotech.dtu.dk.
Abstract
PURPOSE: The objective of this study was to evaluate the potential of PEGylated (64)Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated (177)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 (64)Cu- and (177)Lu-loading efficiency. The tumor imaging potential of (64)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 (64)Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of (177)Lu-liposomes. RESULTS: High remote loading efficiency (>95 %) was obtained for both (64)Cu and (177)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 (64)Cu-liposomes estimated an acceptable total effective dose of 3.3·10(-2) mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic (177)Lu-liposomes. CONCLUSION: The overall preclinical profile of PEGylated (64)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 (64)Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated (64)Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for (177)Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of (177)Lu-liposomes in animals before potential testing in man.
PURPOSE: The objective of this study was to evaluate the potential of PEGylated (64)Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated (177)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 (64)Cu- and (177)Lu-loading efficiency. The tumor imaging potential of (64)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 (64)Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of (177)Lu-liposomes. RESULTS: High remote loading efficiency (>95 %) was obtained for both (64)Cu and (177)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 (64)Cu-liposomes estimated an acceptable total effective dose of 3.3·10(-2) mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic (177)Lu-liposomes. CONCLUSION: The overall preclinical profile of PEGylated (64)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 (64)Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated (64)Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for (177)Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of (177)Lu-liposomes in animals before potential testing in man.
Entities:
Keywords:
Cancer imaging; Diagnostic; Nanoparticle; PET; Radiotherapy; Theranostic
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