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In vivo evaluation of PEGylated 64 Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00259-015-3272-6 Byline: Anncatrine Luisa Petersen (1,2), Jonas Rosager Henriksen (2,3), Tina Binderup (4), Dennis Ringkjobing Elema (2,5), Palle Hedengran Rasmussen (... Full description

Journal Title: European Journal of Nuclear Medicine and Molecular Imaging 2016, Vol.43(5), pp.941-952
Main Author: Petersen, Anncatrine
Other Authors: Henriksen, Jonas , Binderup, Tina , Elema, Dennis , Rasmussen, Palle , Hag, Anne , Kjær, Andreas , Andresen, Thomas
Format: Electronic Article Electronic Article
Language: English
Subjects:
PET
ID: ISSN: 1619-7070 ; E-ISSN: 1619-7089 ; DOI: 10.1007/s00259-015-3272-6
Link: http://dx.doi.org/10.1007/s00259-015-3272-6
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recordid: springer_jour10.1007/s00259-015-3272-6
title: In vivo evaluation of PEGylated 64 Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT
format: Article
creator:
  • Petersen, Anncatrine
  • Henriksen, Jonas
  • Binderup, Tina
  • Elema, Dennis
  • Rasmussen, Palle
  • Hag, Anne
  • Kjær, Andreas
  • Andresen, Thomas
subjects:
  • Nanoparticle
  • Theranostic
  • Cancer imaging
  • Diagnostic
  • PET
  • Radiotherapy
ispartof: European Journal of Nuclear Medicine and Molecular Imaging, 2016, Vol.43(5), pp.941-952
description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00259-015-3272-6 Byline: Anncatrine Luisa Petersen (1,2), Jonas Rosager Henriksen (2,3), Tina Binderup (4), Dennis Ringkjobing Elema (2,5), Palle Hedengran Rasmussen (5), Anne Mette Hag (4), Andreas KjA[bar]r (4), Thomas Lars Andresen (1,2) Keywords: Nanoparticle; Theranostic; Cancer imaging; Diagnostic; PET; Radiotherapy Abstract: Purpose The objective of this study was to evaluate the potential of PEGylated 64.sup.Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated 177.sup.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.sup.Cu- and 177.sup.Lu-loading efficiency. The tumor imaging potential of 64.sup.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.sup.Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of 177.sup.Lu-liposomes. Results High remote loading efficiency (>95 %) was obtained for both 64.sup.Cu and 177.sup.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 [degrees]C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2[+ or -]0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the 64.sup.Cu-liposomes estimated an acceptable total effective dose of 3.3*10.sup.-2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177.sup.Lu-liposomes. Conclusion The overall preclinical profile of PEGylated 64.sup.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.sup.Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated 64.sup.Cu-liposomes in a clinical research programme. The high absorbed tumor dose
language: eng
source:
identifier: ISSN: 1619-7070 ; E-ISSN: 1619-7089 ; DOI: 10.1007/s00259-015-3272-6
fulltext: fulltext
issn:
  • 1619-7089
  • 16197089
  • 1619-7070
  • 16197070
url: Link


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titleIn vivo evaluation of PEGylated 64 Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT
creatorPetersen, Anncatrine ; Henriksen, Jonas ; Binderup, Tina ; Elema, Dennis ; Rasmussen, Palle ; Hag, Anne ; Kjær, Andreas ; Andresen, Thomas
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descriptionTo access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00259-015-3272-6 Byline: Anncatrine Luisa Petersen (1,2), Jonas Rosager Henriksen (2,3), Tina Binderup (4), Dennis Ringkjobing Elema (2,5), Palle Hedengran Rasmussen (5), Anne Mette Hag (4), Andreas KjA[bar]r (4), Thomas Lars Andresen (1,2) Keywords: Nanoparticle; Theranostic; Cancer imaging; Diagnostic; PET; Radiotherapy Abstract: Purpose The objective of this study was to evaluate the potential of PEGylated 64.sup.Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated 177.sup.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.sup.Cu- and 177.sup.Lu-loading efficiency. The tumor imaging potential of 64.sup.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.sup.Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of 177.sup.Lu-liposomes. Results High remote loading efficiency (>95 %) was obtained for both 64.sup.Cu and 177.sup.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 [degrees]C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2[+ or -]0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the 64.sup.Cu-liposomes estimated an acceptable total effective dose of 3.3*10.sup.-2 mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic 177.sup.Lu-liposomes. Conclusion The overall preclinical profile of PEGylated 64.sup.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.sup.Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated 64.sup.Cu-liposomes in a clinical research programme. The high absorbed tumor dose (114 mGy/MBq) estimated for 177.sup.Lu-liposomes and the preliminary dosimetric studies justify further therapeutic and dosimetry investigation of 177.sup.Lu-liposomes in animals before potential testing in man. Author Affiliation: (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 Article History: Registration Date: 27/11/2015 Received Date: 06/08/2015 Accepted Date: 27/11/2015 Online Date: 08/12/2015
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