OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Enhanced efficacy of combined <sup>213</sup>Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest.

PuSH - Publication Server of Helmholtz Zentrum München

Vallon, M.* ; Seidl, C.* ; Blechert, B.* ; Li, Z.* ; Gilbertz, K.P.* ; Baumgart, A.* ; Aichler, M. ; Feuchtinger, A. ; Gaertner, F.C.* ; Bruchertseifer, F.* ; Morgenstern, A.* ; Walch, A.K. ; Senekowitsch-Schmidtke, R.* ; Essler, M.*

Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest.

Eur. J. Nucl. Med. Mol. Imaging 39, 1886-1897 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
PURPOSE: Targeted therapy with α-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the α-emitter (213)Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined (213)Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either (213)Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. METHODS: Cytotoxicity of treatment with (213)Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. RESULTS: Treatment of OVCAR-3 cells in vitro with combined (213)Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either (213)Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with (213)Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 μg) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with (213)Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either (213)Bi-DTPA-F3 or paclitaxel alone. CONCLUSION: Combined treatment with (213)Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords α-emitter 213bi ; Anticancer Drug Paclitaxel ; Peritoneal Carcinomatosis ; Targeted Radionuclide Therapy ; Tumour-homing Peptide F3
ISSN (print) / ISBN 1619-7070
e-ISSN 1432-105X
Journal European Journal of Nuclear Medicine and Molecular Imaging
Quellenangaben Volume: 39, Issue: 12, Pages: 1886-1897 Article Number: , Supplement: ,
Publisher Springer
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)