uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
[(177)Lu]pertuzumab: experimental studies on targeting of HER-2 positive tumour cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
Show others and affiliations
2005 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, Vol. 32, no 12, 1457-62 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The new antibody pertuzumab (Omnitarg) targets the dimerisation subdomain of HER-2. The purpose of this study was to analyse whether pertuzumab retains HER-2 targeting capacity after labelling with the therapeutically interesting beta emitter (177)Lu and to make initial characterizations in vitro and in vivo. METHODS: Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A''-DTPA and chelated to (177)Lu. Immunoreactivity, affinity, cellular retention and internalisation were analysed using SKOV-3 cells. The affinity of non-radioactive pertuzumab was measured using a surface plasmon resonance biosensor. In vivo targeting and specific binding were assessed in Balb/c (nu/nu) mice carrying SKOV-3 xenografts. The biodistribution of (177)Lu was determined 1, 3 and 7 days after [(177)Lu]pertuzumab administration. Gamma camera images were taken after 3 days. RESULTS: The immunoreactivity of [(177)Lu]pertuzumab was 85.8+/-1.3%. The affinity of non-radioactive pertuzumab was 1.8+/-1.1 nM, and that of [(177)Lu]pertuzumab, 4.1+/-0.7 nM. The cellular retention after 5 h pre-incubation was 90+/-2% at 20 h. The targeting was HER-2 specific both in vitro and in vivo, since excess amounts of non-labelled antibody inhibited the uptake of labelled antibody (p<0.0001 and p<0.01, respectively). The biodistribution and gamma camera images of (177)Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake. CONCLUSION: Pertuzumab was efficiently labelled with (177)Lu and showed good intracellular retention and HER-2 specific binding both in vitro and in vivo. The gamma camera images and the biodistribution study gave excellent tumour targeting results. Thus, [(177)Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy.

Place, publisher, year, edition, pages
2005. Vol. 32, no 12, 1457-62 p.
Keyword [en]
Cancer, Tumor, Radiation, Therapy
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-104461DOI: 10.1007/s00259-005-1902-0PubMedID: 16193312OAI: oai:DiVA.org:uu-104461DiVA: diva2:219878
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2009-12-11Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Persson, MikaelTolmachev, VladimirAndersson, KarlGedda, LarsSandström, MattiasCarlsson, Jörgen

Search in DiVA

By author/editor
Persson, MikaelTolmachev, VladimirAndersson, KarlGedda, LarsSandström, MattiasCarlsson, Jörgen
By organisation
Biomedical Radiation Sciences
In the same journal
European Journal of Nuclear Medicine and Molecular Imaging
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 729 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf