Characterization of Blood-Borne Radiolabel and Detection of Anti-Mouse IgG Antibodies in Cancer Patients Receiving Radiolabelled Monoclonal Antibody for Diagnostic Immunoscintigraphy

Pimm, M. V.; Perkins, Alan C.; Rowe, Rachel; Armitage, N. C.; Baldwin, R. W.

doi:10.1007/978-94-009-4297-4_31

Cited by 15 publications

(20 citation statements)

References 9 publications

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“…It can be seen that the ratios increased with time. This in crease presumably reflects the continuing clearance of the antibody fragment from the blood pool while that in the tumor is retained, as has been previously reported [33,34], Our results suggest that the tumor/normal tissue ratio of antibody fragments is still increasing Fig. 3.…”

Section: Analysis O F Labelled Productsupporting

confidence: 73%

Quantitation of Metastatic Tumor Burden from Human Colon Tumor Xenografts using Radiolabelled Monoclonal Antibody 17-A Fragments

et al. 1992

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In realistic models of human tumor xenograft metastasis, the metastatic foci arise in perivascular sites and rarely grow to sizes which are easily quantifiable by visual inspection. As an alternative approach, we have used monoclonal antibody (MAb) 17–1A F(ab′)₂ fragments labelled with radioiodine (¹²⁵I) to study the differential accumulation of label in xenografts and metastatic tumor sites as well as in noninvolved tissues of NIH Swiss nude mice receiving HT-29 human colon tumor cells. Images of the whole-body distribution and sites of localization were determined using a pinhole-collimated Angergamma camera. Radioactivity was determined in tissue samples using a well scintillation system, and pharmacokinetics were assessed during the initial 72 h after injection of antibody fragments. The half-life of ¹²⁵I-F(ab′)₂ fragments in the blood, 8.6 h, was similar in nontumor-bearing control and tumor-bearing mice. The half-life in subcutaneous tumor xenografts was 30.1 h. The tumor xenograft to tissue activity ratios per unit weight (radiolocalization indices) at 72 h were: blood 90, lung 65, pancreas 50, muscle 35, spleen 20, liver and mesenteric lymph node 10. All subcutaneous xenografts were successfully imaged, and images of 5 of 9 mice (55 %) appeared to demonstrate the presence of metastatic tumor by differential and focal accumulation of MAb fragments after 48 or 72 h in the lung (2 cases) or abdominal cavity (3 cases). Necropsy and subsequent histological and biodistribution studies confirmed the presence of metastatic tumor in these sites and identified tumor in several additional sites. The smallest volume of metastatic tissue in liver or lung determined at necropsy which appeared to have been detected by imaging was about 20 mm³. Generally, for mice with metastatic tumors, the radioactivity per unit weight of metastatic tumor-bearing organs compared to tumor-free organs was 2- to 7-fold greater. The results indicate that a radiolocalization index of ≥ 2 is generally necessary for metastatic tumor detection by imaging although this is influenced by the extent of anatomical location of the tumor. It was possible to predict the tissue distribution of the fragments from the planar image for the amounts of radioactivity (approximately 1 mCi/kg body weight) employed in this study. These results demonstrate the utility of this approach to quantitate the metastatic burden arising from human colon tumor xenografts in this experimental model.

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Section: Analysis O F Labelled Productsupporting

confidence: 73%

Quantitation of Metastatic Tumor Burden from Human Colon Tumor Xenografts using Radiolabelled Monoclonal Antibody 17-A Fragments

et al. 1992

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“…However, murine antibodies are known to solicit an 'anti-mouse' response from the human immune system (Pimm et al, 1985;Reynolds et al, 1986) and this could seriously diminish their clinical usefulness. Although such materials can be 'humanized,' the most satisfactory procedure would be to use a wholly human antibody.…”

Section: Discussionmentioning

confidence: 99%

14C1, an antigen associated with human ovarian cancer, defined using a human IgG monoclonal antibody

Gallagher

Al‐Azzawi

Walsh

et al. 1991

Clinical and Experimental Immunology

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SUMMARYWe bave selected a buman EBV-transformed cell line from tbe involved lympb nodes of an ovarian cancer patient wbicb secretes an IgG 1 K antibody, able to recognize an antigen present on Ibe surface of ovarian cancer cells. The antigen, termed ' 14C1,' bas previously been shown by immunobistological tecbniques to be present on tbe surface of tbe malignant cells witbin tumour specimens. Western blotting analysis bas sbown Ibat tbe majority of primary ovarian cancer specimens and tbree continuous cell lines derived tberefrom express 14CI; otber tissue types were negative. Preliminary biocbemical cbaracterization bas been carried out, wbicb sbows tbat tbe 14CI antigen bas a molecular weight range of 25-32 kD and an isoelectric point from pf 6-3 to 6S. We believe that the 14C1 antigen is immunologically relevant to ovarian cancer patients and may tberefore represent a novel target for botb active and passive immunotherapy.

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“…There is already evidence that patients can develop antimouse antibodies (Pimm et al, 1985b) and these may inactivate or modify the administered antibody. Alternatively antibody may become non specifically attached to circulating cellular components.…”

Section: Discussionmentioning

confidence: 99%

Localisation of gastrointestinal cancer with a 131 I labelled monoclonal antibody to CEA

Allum¹,

Macdonald²,

Anderson³

et al. 1986

Br J Cancer

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Characterization of Blood-Borne Radiolabel and Detection of Anti-Mouse IgG Antibodies in Cancer Patients Receiving Radiolabelled Monoclonal Antibody for Diagnostic Immunoscintigraphy

Cited by 15 publications

References 9 publications

Quantitation of Metastatic Tumor Burden from Human Colon Tumor Xenografts using Radiolabelled Monoclonal Antibody 17-A Fragments

Quantitation of Metastatic Tumor Burden from Human Colon Tumor Xenografts using Radiolabelled Monoclonal Antibody 17-A Fragments

14C1, an antigen associated with human ovarian cancer, defined using a human IgG monoclonal antibody

Localisation of gastrointestinal cancer with a 131 I labelled monoclonal antibody to CEA

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