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

Direct link
Effect of closo-dodecarborate-containg linker on targeting HNSCC xenografts with radio-iodinated chimeric monoclonal antibody U36. Dual isotope comparative biodistribution study
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
Show others and affiliations
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-93172OAI: oai:DiVA.org:uu-93172DiVA: diva2:166568
Available from: 2005-04-27 Created: 2005-04-27 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Radioimmunotherapy in Experimental Head and Neck Squamous Cell Carcinoma: Tumour-targeting in vitro and in vivo
Open this publication in new window or tab >>Radioimmunotherapy in Experimental Head and Neck Squamous Cell Carcinoma: Tumour-targeting in vitro and in vivo
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Radioimmunotherapy (RIT) has been shown to be a practicable way to treat head and neck squamous cell carcinoma. A specific antibody recognizes the charasteristic structure of tumour cells when loaded with cytotoxic agents (toxins, drugs, radionuclides, etc). But RIT kills not only tumour cells with attached radionuclides but also adjacent tumour cells due to the “cross fire effect”. To be efficacious, RIT depends closely on suitable monoclonal antibody, on the properties of the chosen radionuclides, and on a suitable labelling method for attaching radionuclide to antibody.

In this study we initially used radionuclide-labelled cMAB U36, via linker DABI in order to improve the retention of radio-conjugates in the tumour cells. Improved retention is important because the longer the radionuclide remains in tumour cells, the more effective will the tumour cells be eradicated. In the investigation, both normal mice and HNSCC-bearing nude mice were used to compare our form of treatment against other radio-iodination methods. In the biodistribution study, normal mice showed that radioactive uptake in organs diminished with time, irrespectively of whether the conjugate was directly or indirectly labelled. But in thyroid, there was a tenfold greater accumulation of direct-labelled than of indirectly labelled conjugate.

In tumour-bearing nude mice, by contrast, the results showed promising uptake of radioactivity, but little uptake in direct-labelled conjugate in thyroid. Significant differences were observed on comparing tumour: organ ratios between 131I-cMAb U36 vs. 125I-DABI-cMAb U36.

In the present study, cMAb U36 labelled with 211Astatine was initially used to treat HNSCC in nude mice. The biodistribution of 211At-cMAb U36 did not reveal any significant difference between an antibody-blocked group and a non-blocked group. But it did highlight the characteristics of a successful targeting conjugate in HNSCC-bearing nude mice.

In the subcutaneous therapy experiment, most of the treated tumours (n=18) had disappeared by the 26th day, in both U36-blocked and non-blocked groups. Treatment in the intravenous therapy experiment had also proved effective. In the antibody non-blocked group, the smallest tumour volume was 25 mm3 (average 111 mm3) vis-á-vis 65 mm3 (average 145 mm3) in the blocked group. None of tumours grew again following treatment.

42 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 49
Otorhinolaryngology, squamous cell carcinoma, radioimmunotherapy, cell line, tumour targeting, radionuclide, nude mice, Otorhinolaryngologi
National Category
urn:nbn:se:uu:diva-5834 (URN)91-554-6277-4 (ISBN)
Public defence
2005-05-18, Skoogsalen, NOP-huset, Akademiska sjukhuset, Uppsala, 09:15
Available from: 2005-04-27 Created: 2005-04-27Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Surgical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 179 hits
ReferencesLink to record
Permanent link

Direct link