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Quantification of CD44v6 and EGFR expression in head and neck squamous cell carcinomas using a single-dose radioimmunoassay
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2007 (English)In: Tumor Biology, ISSN 1010-4283, Vol. 28, no 5, 253-263 p.Article in journal (Refereed) Published
Abstract [en]

Background: In the growing field of tumor targeting, there is an urgent need to profile suitable molecular targets. In this study, CD44v6 and EGFR expression was quantified in samples of patients with head and neck squamous cell carcinoma (HNSCC) using a single-dose (SD) radioimmunoassay. Methods: The SD radioimmunoassay using 125I-chimeric monoclonal antibody (cMAb) U36 and 125I-cMAb cetuximab was first validated and then applied to quantify the expression of their target antigen molecules, CD44v6 and EGFR, in patient samples. Results were compared to immunohistochemical staining. Results: The SD assay provided sensitive quantitative values of the molecular targets studied, generally agreeing with the immunohistochemistry (IHC) results. The results indicated that expression of CD44v6 (0.2-20 nmol/μg membrane) was generally higher than that of EGFR (0.6-2.3 nmol/μg membrane) in the tumor samples analyzed, which corresponded to an average of 700,000 and 90,000 antigen molecules per cell, respectively. Conclusions: The SD radioimmunoassay is simple, reliable, and can be performed on a small amount (50 mg) of tissue. This assay could be a useful tool in the growing field of personalized cancer therapy, and can be used as a complement to IHC. In the tumors studied, CD44v6 was generally expressed at a higher level than EGFR, which might suggest that it could be more readily targeted by MAbs.

Place, publisher, year, edition, pages
2007. Vol. 28, no 5, 253-263 p.
Keyword [en]
CD44v6, EGFR, Head and neck squamous cell carcinoma, Quantification, Radioimmunoassay
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95172DOI: 10.1159/000110898ISI: 000250896300002PubMedID: 17992053OAI: oai:DiVA.org:uu-95172DiVA: diva2:169287
Available from: 2006-11-24 Created: 2006-11-24 Last updated: 2016-02-08Bibliographically approved
In thesis
1. Antibody-Based Radionuclide Targeting for Diagnostics and Therapy: Preclinical Studies on Head and Neck Cancer
Open this publication in new window or tab >>Antibody-Based Radionuclide Targeting for Diagnostics and Therapy: Preclinical Studies on Head and Neck Cancer
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Antibody-based targeting techniques play an increasingly important role in cancer research. By targeting a structure that is abundant in tumour cells, but rare in healthy tissues, an antibody can mediate the delivery of radioactivity specifically to tumour cells in the body. This idea is particularly appealing for head and neck squamous cell carcinoma (HNSCC), as the advanced stages have a large fraction of spread disease that is difficult to treat with procedures available today.

In this thesis, we have investigated possible radioimmunotargeting structures for HNSCC, and found that CD44v6 is a suitable target for antibody-based radiotherapy and diagnostics in this patient group. We have identified radiohalogens as attractive nuclides for such use, and have investigated the possibility of radiohalogenating the anti CD44v6 chimeric monoclonal antibody (cMAb) U36. Several feasible labelling methods were identified, using both direct and indirect labelling. The cMAb U36 was then successfully labelled with 211At and 131I, and preclinically evaluated for therapeutic use. Results proved the astatinated conjugate to be most efficient in this context, demonstrating a specific and dose-dependent cytotoxicity. The cMAb U36 was then evaluated for diagnostic use in thyroid anaplastic carcinoma, using 124I as the diagnostic nuclide. Results in tumour-bearing mice were promising, with all of the tumours identified in micro-PET studies.

These results demonstrate how antibody-based radionuclide targeting can provide more sensitive and specific methods for identifying and treating head and neck cancer, and hopefully help improve long-term survival rates for this patient group in the future.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 48 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 204
Keyword
Otorhinolaryngology, antibodies, radionuclide targeting, tumour targeting, therapy, diagnostics, immuno-PET, head and neck squamous cell carcinoma, Otorhinolaryngologi
Identifiers
urn:nbn:se:uu:diva-7341 (URN)91-554-6729-6 (ISBN)
Public defence
2006-12-15, Rudbeck lecture hall, Rudbeck laboratory, Dag Hammarskölds väg 20, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-11-24 Created: 2006-11-24 Last updated: 2011-01-18Bibliographically approved

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Nestor, MarikaTolmachev, Vladimir

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Department of Surgical SciencesDepartment of Oncology, Radiology and Clinical ImmunologyOtolaryngology and Head and Neck Surgery
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