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dc.contributor.author
Lindenblatt, Dennis
dc.contributor.author
Fischer, Eliane
dc.contributor.author
Cohrs, Susan
dc.contributor.author
Schibli, Roger
dc.contributor.author
Grünberg, Jürgen
dc.date.accessioned
2019-04-05T06:39:38Z
dc.date.available
2017-06-11T18:49:52Z
dc.date.available
2019-04-05T06:39:38Z
dc.date.issued
2014-10
dc.identifier.other
10.1186/s13550-014-0054-2
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/103325
dc.identifier.doi
10.3929/ethz-b-000103325
dc.description.abstract
Background Today's standard treatment of advanced-stage ovarian cancer, including surgery followed by a paclitaxel-platinum-based chemotherapy, is limited in efficacy. Recently, we could show that radioimmunotherapy (RIT) with 177Lu-labelled anti-L1 cell adhesion molecule (L1CAM) monoclonal antibody chCE7 is effective in ovarian cancer therapy. We investigated if the efficacy of anti-L1CAM RIT can be further improved by its combination with paclitaxel (PTX). Methods In vitro cell viability and cell cycle arrest of human ovarian cancer cells were assessed upon different treatment conditions. For therapy studies, nude mice (n = 8) were injected subcutaneously with IGROV1 human ovarian carcinoma cells and received a single dose of 6 MBq 177Lu-DOTA-chCE7 alone or in combination with 600 μg PTX (31.6 mg/kg). Tumour growth delay and survival were determined. To investigate whether PTX can influence the tumour uptake of the radioimmunoconjugates (RICs), a biodistribution study (n = 4) and SPECT/CT images were acquired 120 h post injections of 2 MBq 177Lu-DOTA-chCE7 alone or in combination with 600 μg PTX. Results Lu-DOTA-chCE7 in combination with PTX revealed a significantly decreased cell viability of ovarian carcinoma cells in vitro and was effective in a synergistic manner (combination index < 1). PTX increased the RIT efficacy by arresting cells in the radiosensitive G2/M phase of the cell cycle 24 h post treatment start. In vivo combination therapy including 177Lu-DOTA-chCE7 and PTX resulted in a significantly prolonged overall survival (55 days vs. 18 days/PTX and 29 days/RIT), without weight loss and/or signs of toxicity. Biodistribution studies revealed no significant difference in tumour uptakes of 177Lu-DOTA-chCE7 72 h post injection regardless of an additional PTX administration. Conclusions Combination of anti-L1CAM 177Lu-RIT with PTX is a more effective therapy resulting in a prolonged overall survival of human ovarian carcinoma-bearing nude mice compared with either monotherapy. The combination is promising for future clinical applications.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Lu-177-radioimmunotherapy
en_US
dc.subject
Paclitaxel
en_US
dc.subject
Combination therapy
en_US
dc.subject
Ovarian
en_US
dc.subject
carcinoma
en_US
dc.subject
L1CAM
en_US
dc.subject
mAb chCE7
en_US
dc.title
Paclitaxel improved anti-L1CAM lutetium-177 radioimmunotherapy in an ovarian cancer xenograft model
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2014-10-03
ethz.journal.title
EJNMMI Research
ethz.journal.volume
4
en_US
ethz.pages.start
54
en_US
ethz.size
10 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
Heidelberg
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-11T18:50:21Z
ethz.source
ECIT
ethz.identifier.importid
imp59365365125ee66596
ethz.ecitpid
pub:161539
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T02:17:47Z
ethz.rosetta.lastUpdated
2019-04-05T06:39:44Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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