Superior localisation and imaging of radiolabelled monoclonal antibody E48 F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody E48 IgG

Autor: M. Gerretsen, Jasper J. Quak, C. J. L. M. Meijer, J. S. Suh, G.A.M.S. (Guus) van Dongen, G. B. Snow, M. Van Walsum
Přispěvatelé: General practice, Otolaryngology / Head & Neck Surgery, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, AII - Cancer immunology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, AII - Inflammatory diseases
Jazyk: angličtina
Rok vydání: 1991
Předmět:
Zdroj: British Journal of Cancer
British Journal of Cancer, 63(1), 37-44. Nature Publishing Group
Gerretsen, M, Quak, J J, Suh, J S, Van Walsum, M, Meijer, C J L M, Snow, G B & Van Dongen, G A M S 1991, ' Superior localisation and imaging of radiolabelled monoclonal antibody e48 f(ab') 2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody e48 igg ', British Journal of Cancer, vol. 63, no. 1, pp. 37-44 . https://doi.org/10.1038/bjc.1991.9
ISSN: 1532-1827
0007-0920
DOI: 10.1038/bjc.1991.9
Popis: Monoclonal antibody (MAb) E48 and its F(ab')2 fragment, radiolabelled with1311, were tested for tumour localisation and imaging in nude mice bearing a squamous cell carcinoma xenograft line derived from a head and neck carcinoma (HNX-HN) or from a vulva carcinoma (VX-A431). MAb IgG or F(ab')2fragments were injected in parallel and at day 1, 2, 3 and 6 or 7, mice were either scanned with a gamma camera or dissected for determination of isotope biodistribution. In HNX-HN bearing mice, E48 IgG as well as F(ab')2 showed highly specific localisation in tumour tissue. The mean tumour uptake (n = 4) expressed as the percentage of the injected dose per gram of tumour tissue (percentage ID/g) of IgG was 11. 9% at day 1 and increased to 14. 6% at day 6 whereas percentage ID/g of F(ab')2 was 7. 2% at day 1 and decreased during subsequent days. Tumour to blood ratios (T/B) at day 1 were 1. 2 for IgG and 13. 6 for F(ab')2 and reached a maximum at day 6 with values of 6. 4 and 54. 2 respectively. In VX-A431 bearing mice, only E48 F(ab')2showed preferential localisation in tumour tissue. At day 1, Percentage ID/g of IgG was 3. 7 and T/B was 0. 3, while percentage ID/g of F(ab')2 was 2. 4 and T/B was 3. 2. Percentage ID/g decreased after day 1 while T/B increased. In these experiments no preferential localisation of either isotype matched25I-labelled control IgG or F(ab')2 was observed. In F(ab')2 injected HNX-HN bearing mice as well as VX-A431 bearing mice, tumours could be visualised at day 1 and 2 without any appreciable background activity. With MAb IgG this was also possible in HNX-HN bearing mice (but not in VX-A431 bearing mice) but only at day 3 and 6. These findings suggest that the superior tumour to non-tumour ratios render the E48 F(ab')2 fragment more qualified for specific targeting of radioisotopes to tumour xenografts in this experimental setting.
Databáze: OpenAIRE