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Radioimmunotherapy in Experimental Head and Neck Squamous Cell Carcinoma: Tumour-targeting in vitro and in vivo
Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
2005 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
2005. , s. 42
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 49
Emneord [en]
Otorhinolaryngology, squamous cell carcinoma, radioimmunotherapy, cell line, tumour targeting, radionuclide, nude mice
Emneord [sv]
Otorhinolaryngologi
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-5834ISBN: 91-554-6277-4 (tryckt)OAI: oai:DiVA.org:uu-5834DiVA, id: diva2:166570
Disputas
2005-05-18, Skoogsalen, NOP-huset, Akademiska sjukhuset, Uppsala, 09:15
Opponent
Veileder
Tilgjengelig fra: 2005-04-27 Laget: 2005-04-27bibliografisk kontrollert
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3. Effect of closo-dodecarborate-containg linker on targeting HNSCC xenografts with radio-iodinated chimeric monoclonal antibody U36. Dual isotope comparative biodistribution study
Åpne denne publikasjonen i ny fane eller vindu >>Effect of closo-dodecarborate-containg linker on targeting HNSCC xenografts with radio-iodinated chimeric monoclonal antibody U36. Dual isotope comparative biodistribution study
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Manuskript (Annet vitenskapelig)
Identifikatorer
urn:nbn:se:uu:diva-93172 (URN)
Tilgjengelig fra: 2005-04-27 Laget: 2005-04-27 Sist oppdatert: 2010-01-13bibliografisk kontrollert
4. Radioimmunotherapy with 211 Astatine, using chimeric monoclonal antibody U36 in hed and neck squamous cell carcinoma in vivo
Åpne denne publikasjonen i ny fane eller vindu >>Radioimmunotherapy with 211 Astatine, using chimeric monoclonal antibody U36 in hed and neck squamous cell carcinoma in vivo
Vise andre…
Manuskript (Annet vitenskapelig)
Identifikatorer
urn:nbn:se:uu:diva-93173 (URN)
Tilgjengelig fra: 2005-04-27 Laget: 2005-04-27 Sist oppdatert: 2010-01-13bibliografisk kontrollert

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