Clinical Value of Imaging Using Antibody to Alpha Fetoprotein in Germ Cell Tumours

Hitchins, R. N.; Begent, R. H. J.; Green, A. J.; Searle, F.; Heyningen, Veronica van; Bagshawe, K. D.

doi:10.1055/s-0038-1629467

Cited by 8 publications

(2 citation statements)

References 12 publications

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“…A5B7 anti-CEA (Harwood et al, 1986) and A161 (Hitchens et al, 1989) anti-alphafetoprotein antibodies were labelled (Fraker and Speck, 1978) with 125 I (21.5-120.5 MBq mg Ϫ1 and 104 MBq mg Ϫ1 respectively) passed through a 0.22 µm filter (Gellman Ltd, Northampton, UK). Percentage incorporation of 125 I into antibody was calculated, from thin layer chromatographs (TLC) on 0.25-mm silica gel (Macherey-Nagel, Polytron sil G/UV 254), using phosphor image plate technology (see later).…”

Section: Antibodiesmentioning

confidence: 99%

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome

et al. 1999

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Many diseases are characterized by altered expression of proteins or peptide antigens which define diagnosis or disease behaviour. The biological significance of an antigen is generally dependent on its concentration and there is a need for a means of measuring antigen concentration in tissue sections. Visualization of tissue morphology is important because antigen expression is commonly related to a particular cell population within a mixed tissue. Immunohistochemistry (IHC) retains tissue morphology but does not reliably quantitate antigen while assays of extracts of homogenized tissue involve destruction of morphology.The principal aim of this work was, first, to establish and validate a method for quantifying protein concentration in histological sections of colorectal cancer and then, second, to apply this technique to a clinically relevant situation.Radioimmunoluminography (RILG), a generally applicable method for measurement of antigen concentration in tissue sections, is based on quantification of radiolabelled antibody binding to tissue sections using a phosphor plate imager. The amount of antibody bound in a given area of the section will be proportional to the amount of antigen present if saturating concentrations of antibody are used. The distribution of radioactivity in a section is mapped by a phosphor plate imager which quantitates antigen-bound antibody pixel by pixel in the digital image. The high sensitivity and linear response over five orders of magnitude of this instrument (Chung et al, 1994;Okuyama et al, 1994) make it practical to quantitate the very small amounts of radioactivity present. The pixel size of available phosphor imagers (25-90 µm) gives sufficient resolution for correlation with light microscope images. Here we show that the concentration of carcinoembryonic antigen (CEA) in histological sections can be quantitated using a calibration line constructed from RILG binding to known amounts of CEA. The accuracy of RILG has been established by assessing CEA levels in sections of human colon carcinoma xenografts.In antibody-directed targeted therapy of cancer the localization of anti-tumour antibodies in tumours varies greatly between individual patients and as yet the factors responsible for this variation have not been critically defined (Boxer et al, 1992). Whilst there have been a number of papers implicating a variety of putative cellular and physiological factors (Jain, 1989;Poznansky and Juliano, 1984;Shockley et al, 1991) there has been surprisingly little attention paid to the importance of tumour antigen concentration. The ability of RILG to directly measure CEA concentration in biopsies is shown to be clinically useful and can enable us to predict the likely efficiency of antibody-targeted therapy of colorectal carcinoma. MATERIALS AND METHODS Tissue preparationHuman adenocarcinoma xenografts (Pedley et al, 1996) with different levels of CEA expression, SW116, LS174T(1), LS174T(2), HT29/219 (colon), OVCA (ovarian), PAPA (breast) and a CEA-negative, rat mammary (RM) tumour...

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Section: Antibodiesmentioning

confidence: 99%

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome

et al. 1999

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“…Although AFP is a secretary protein, it is also retarded at the cell surface before release. For diagnostic purposes, radiolabelled monoclonal antibody against AFP has been used in imaging germ cell tumors (2) and HCC (3,4). Thus, monoclonal antibodies against AFP could also be used in targeting HCC and teratocarcinomas(5,6) in therapeutic application.…”

Section: Introductionmentioning

confidence: 99%

Characterization and Nucleotide Sequences of the Variable Regions of a Monoclonal Antibody against α-Fetoprotein

Hong

Hsiao²,

Sheu³

et al. 1992

Hybridoma

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alpha-Fetoprotein (AFP) is a well-known tumor marker of hepatocellular carcinoma (HCC). Monoclonal antibodies against AFP possessing specific binding ability to HCC are potential candidates for immunoscintigraphy and immunotherapy. A new monoclonal antibody against AFP (0325-6-9) was isolated. Its specificity and targeting tumor ability were characterized by enzyme-linked immunosorbent assay (ELISA), cell immunostain and complement killing. These results suggest that 0325-6-9 is specific to hepatoma cells. The nucleotide sequences of variable regions of 0325-6-9 were determined by M13 dideoxynucleotide sequencing method. With the information of nucleotide sequence, this antibody then could be modified by recombinant technology for its usage in in vivo diagnosis and immunotherapy.

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Alpha-Fetoprotein in the 1990s

Taketa¹

1992

Serological Cancer Markers

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Clinical Value of Imaging Using Antibody to Alpha Fetoprotein in Germ Cell Tumours

Cited by 8 publications

References 12 publications

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome

Radioimmunoluminography: a tool for relating tissue antigen concentration to clinical outcome

Characterization and Nucleotide Sequences of the Variable Regions of a Monoclonal Antibody against α-Fetoprotein

Alpha-Fetoprotein in the 1990s

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