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
A novel CD44v6 targeting antibody fragment with improved tumor-to-blood ratio.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-156522OAI: oai:DiVA.org:uu-156522DiVA: diva2:432053
Available from: 2011-07-28 Created: 2011-07-28 Last updated: 2011-08-26
In thesis
1. Radioimmunodiagnosis of Head and Neck Squamous Cell Carcinomas: Preclinical Studies
Open this publication in new window or tab >>Radioimmunodiagnosis of Head and Neck Squamous Cell Carcinomas: Preclinical Studies
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Despite improvements in treatment, the prognosis for patients with advanced head and neck squamous cell carcinomas (HNSCC) has only improved to a minor degree. To raise the success rate and minimize morbidity further developments in diagnostics are highly desired. Radioimmunodiagnosis could offer a more specific and sensitive diagnostic method. Herein, we have evaluated different radioimmunoconjugates directed against CD44v6 and epidermal growth factor receptor (EGFR) for imaging of HNSCC. The studies were performed in a murine HNSCC xenograft model.

Initially, the 111In-labeled anti CD44v6 chimeric monoclonal antibody U36 (cMAb U36) was evaluated. The novel radioimmunoconjugate showed high and accumulating tumor uptake. Since small molecules might be advantageous for imaging, due mainly to their shorter circulation half-life in the bloodstream, we then investigated antibody fragments F(ab’)2 and Fab’ derived from cMAb U36. The highest tumor-to-blood ratio was achieved with the dimeric antibody fragment F(ab’)2, compared with both the intact anti-body and monomeric Fab’.

Furthermore, the possibility of improving EGFR-targeted imaging was explored by pre-blocking EGFR. The liver uptake of injected labeled human epidermal growth factor (hEGF) was significantly reduced when an excess of unlabeled hEGF was injected 30 minutes in advance. However, as hEGF stimulates cell proliferation it may be inadvisable to treat cancer patients with large amounts. Alternatively, pre-blocking with an anti-EGFR Affibody molecule (ZEGFR:955)2 demonstrated similar decrease in liver uptake as unlabeled hEGF. Finally, (ZEGFR:955)2 was compared with other Affibody molecules with higher affinity to EGFR, ZEGFR:1907 and (ZEGFR:1907)2, as pre-blocking agents. In addition, a novel hEGF radioimmunoconjugate, [67Ga]Ga-NOTA-Bn-NCS-hEGF was used for EGFR targeting. The dimeric (ZEGFR:1907)2 showed greatest reduction in non-tumor uptake, and highest tumor-to-organ ratio in EGFR expressing organs, when injected in advance of the radioimmunoconjugate.

To summarize, the results presented here demonstrate how different radioimmunoconjugates as well as pre-blocking EGFR can improve the radioimmunodiagnosis of head and neck squamous cell carcinomas.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 682
Keyword
Head and neck squamos cell carcinoma, radioimmunotargeting, radioimmunodiagnosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-156523 (URN)978-91-554-8111-7 (ISBN)
Public defence
2011-09-16, Skoogsalen, Ing 78-79, Akademiska sjukhuset, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2011-08-25 Created: 2011-07-28 Last updated: 2011-09-08Bibliographically approved

Open Access in DiVA

No full text

By organisation
Otolaryngology and Head and Neck SurgeryOncologyClinical ImmunologyBiomedical Radiation Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 385 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