Localization and imaging of radiolabelled monoclonal antibody against squamous‐cell carcinoma of the head and neck in tumor‐bearing nude mice

Quak, Jasper J.; Balm, Alfons J. M.; Brakkee, J. G. P.; Scheper, R.J.; Haisma, Hidde J.; Braakhuis, B.J.M.; Meijer, Chris J.L.M.; Snow, Gordon B.

doi:10.1002/ijc.2910440327

Cited by 23 publications

(12 citation statements)

References 11 publications

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“…Node-negative neck disease conventionally refers to clinically non-palpable neck nodes but this is a grossly inadequate and inaccurate method of identifying metastatic neck node [4,21,114,121,133]. Researchers have demonstrated that clinical N0 necks have shown occult metastases in about 30% or higher, depending on the size, site of primary tumor and the histological diagnostic methods [21,118].…”

Section: Diagnosing the Node-negative Neckmentioning

confidence: 99%

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

et al. 2011

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Section: Diagnosing the Node-negative Neckmentioning

confidence: 99%

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

et al. 2011

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“…MAb mouse E48 IgG 1 (Quak et al, 1989) is directed against an antigen present on squamous epithelial cells and their neoplastic counterparts. Both MAbs were kindly provided by Centocor (Leiden, The Netherlands).…”

Section: Reagents Mabs and Iodinationmentioning

confidence: 99%

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

et al. 1997

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The epithelial glycoprotein 40 (EGP40) is an important target in the clinic for radioimmunolocalization and monoclonal antibody (MAb)-mediated therapy of cancer. We determined which tumor-related factors (including antigen distribution and density, vascularization and perfusion) were involved in the uptake of the anti-EGP40 MAb 323/A3 in 4 different human ovarian cancer xenografts grown s.c. in nude mice. The reactivity pattern of 323/A3 in all xenografts in vitro was similar and showed a strong and homogeneous distribution of the EGP40 antigen. FMa xenografts, however, showed the highest uptake of 323/A3 in vivo, which was 5.5-, 6.2-and 10.0-fold higher than that in OVCAR-3, Ov.Pe and Ov.Sh xenografts, respectively. FMa xenografts contained 2.1-to 3.5-fold more antigen per gram protein when compared with the antigen content of the other xenografts. FMa and Ov.Sh xenografts demonstrated a better vascularization pattern, whereas Ov.Pe and OVCAR-3 xenografts were moderately to poorly vascularized. FMa xenografts were also better perfused, as was shown by a 1.6-to 1.8-fold higher uptake of the 99m Tc-labeled blood flow marker hexamethylpropyleneamine oxime (HMPAO). The tumor uptake of the non-specific MAb E48 was 2.2-to 11.2-fold lower when compared with that of 323/A3, but the sequence of uptake was similar (FMa G OVCAR-3 5 Ov.Pe G Ov.Sh), indicating the lowest extravasation of MAbs in Ov.Sh xenograft tissue. Since both the antigen content and the perfusion appeared to be important factors of influence on the tumor uptake of 323/A3, attempts were made to manipulate these determinants to improve the tumor uptake. Neither g-interferon nor 5-fluorouracil were able to increase EGP40 expression in human ovarian cancer cells in vitro. Treatment of tumor-bearing mice with the calcium-antagonist flunarizine did not result in an improved perfusion, although a slight increase in the initial tumor uptake of 323/A3 was observed in Ov.Sh-bearing mice. Our results illustrate the relative contribution of various tumorrelated factors that determine the usefulness of a MAb for imaging and therapy of cancer. Int.

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“…Recently, we described the capacity of MAb E48 IgG for highly specific delivery of radioisotopes in nude mice carrying human head and neck SCC xenografts (Quak et al, 1989). However, F(ab')2 fragments have been demonstrated to have better tumour to non-tumour ratios in nude mice bearing xenografts due to a more rapid clearance from the blood (Pervez et al, 1988;Colapinto et al, 1988;Buchegger et al, 1986;Endo et al, 1988).…”

mentioning

confidence: 99%

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

Gerretsen

Quak²,

Suh³

et al. 1991

Br J Cancer

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Monoclonal antibody (MAb) E48 and its F(ab')2 fragment, radiolabelled with 131I, 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')2 fragments 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')2 showed 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 matched 125I-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. Images Figure 1 Figure 2 Figure 6 Figure 7 Figure 8

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Localization and imaging of radiolabelled monoclonal antibody against squamous‐cell carcinoma of the head and neck in tumor‐bearing nude mice

Cited by 23 publications

References 11 publications

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

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

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