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Breast Imaging with Radiolabeled Antibodies
Published in Raymond Taillefer, Iraj Khalkhali, Alan D. Waxman, Hans J. Biersack, Radionuclide Imaging of the Breast, 2021
Lamk M. Lamki, Bruce J. Barron
Besides antibodies to CEA, radiolabeling of other breast cancer antigens, such as tumor-associated glycoprotein and breast epithelial antigen (mucin), have also proven successful. Monoclonal antibody B-72.3 is an IgG subclass which reacts with a 200,000- to 400,000-molecular-weight tumor-associated glycoprotein (TAG-72) antigen [37], Using immunohistologic methods, up to 80% of human breast cancers were found to be reactive with the antibody B72.3 [100],
Regional Therapy of Liver Metastases: A Surgeon’s View
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
RIGS uses a hand-held gamma detector (Neoprobe® 1000) to detect gamma emissions from, for example, 125I-labeled monoclonal antibody localized in tissue. The murine monoclonal antibody B72.3 is an IgG1 that reacts with a high molecular weight (220,000 to 500,000) tumor-associated glycoprotein complex (TAG-72) found on several human cancers of epithelial origin, including colonic adenocarcinoma.23 With this reagent, Nieroda et al.24 used the following protocol in 30 patients with primary colorectal cancer. First, patients were prepared on an oral regimen of supersaturated potassium iodide to saturate the thyroid gland and prevent uptake of 125I-labeled antibody. The patients were also tested for immediate-type hypersensitivity using an intradermal forearm injection of the unlabeled antibody and observing for a reaction after 15 min; no patient had such a reaction. Each patient then received radiolabeled antibody intravenously. The timing of each operation was determined by measuring gamma counts over the heart to assess blood clearance of radiolabel. A mean of 22 days (8 to 34 days) elapsed between injection of the antibody and operation.
Cytokine-Based Modalities to Enhance Monoclonal-Antibody-Mediated Tumor Cell Killing
Published in David M. Goldenberg, Cancer Therapy with Radiolabeled Antibodies, 1995
John W. Greiner, Shinya Shimada, Fiorella Guadagni, Claudio Dansky Ullmann, Carol Nieroda, Jeffrey Schlom
In a previous book edited by Dr. Goldenberg,20 we reported that two human tumor antigens, tumor-associated glycoprotein 72 (TAG-72) and carcinoembryonic antigen (CEA), in some cases, exhibit extensive heterogeneity in their expression in a variety of human carcinoma cell populations. We also reported that interferon treatment could selectively enhance TAG-72 and CEA expression on the surface of human breast and colon carcinoma cells. Finally, it was reported that in vivo administration of IFN-α enhanced the expression of a Mr 90,000 antigen in human colon xenografts, which improved the tumor targeting of the Mr 90.000-reactive-B6.2 MoAb.23 The present chapter will summarize data from several of our most recent experimental studies. They include (1) the analysis of IFN-γ effects on CEA expression and shedding using a broad range of human colon carcinoma cell lines,21,22 (2) identification of a novel gene product in IFN-γ-treated human gastric carcinoma cells,24 and (3) the augmentation of the antitumor effects of an anti-TAG-72 radioimmunoconjugate when combined with an IFN-γ-based protocol that up-regulated TAG-72 expression in a human tumor xenograft model.25
Serum macrophage inhibitory cytokine-1 serves as a novel diagnostic biomarker of early-stage colorectal cancer
Published in Biomarkers, 2021
Chunyang Dai, Xiaolei Zhang, Yanling Ma, Zhaowu Chen, Shaohua Chen, Yang Zhang, Ming Li
The high mortality of CRC is partially attributed to the advanced stage when patients are diagnosed with CRC. Evidence indicates that CRC develops slowly, which allows its detection at an earlier stage via mass screening (Hardcastle et al. 1996). Moreover, early intervention reduces the risk of a fatal outcome (Kronborg et al. 1996). Monitoring serum tumour markers are convenient, rapid, minimally invasive, and inexpensive and is therefore widely used for auxiliary diagnosis. Available tumour biomarkers, such as CEA, CA19-9, and CA24-2 are not sufficiently sensitive and specific for application to the detection of precancerous colorectal lesions and early-stage cancer (Nicolini et al. 2010; Thomas et al. 2015; García-Albéniz et al. 2017). CEA is a tumour-associated glycoprotein that lacks the specificity required to diagnose different tumour types. Furthermore, post-operative CEA is more informative than preoperative CEA (Lin et al. 2011; Konishi et al. 2018). The carbohydrate antigen CA199 is a specific marker for adenocarcinoma, although it lacks organ specificity and can be expressed by malignancies, such as pancreatic cancer, gastric cancer, and CRC (Komori et al. 2017; Gao et al. 2018). The carbohydrate antigen CA242 is frequently used in the clinic to detect CRC; however, CA24-2 does not serve as a specific marker for diagnosing early-stage CRC (Luo et al. 2020).
Mucin-producing hepatic cystic neoplasms: an uncommon but challenging disease often misdiagnosed and mismanaged
Published in Acta Chirurgica Belgica, 2020
J. Frezin, M. Komuta, F. Zech, L. Annet, Y. Horsmans, J. F. Gigot, A. Jouret-Mourin, C. Hubert
Serum tumour markers such as CEA and CA 19-9 have both been reported normal or elevated in MHCN [7,10,11,13,26,32]. In our series, only three out of nine patients presented elevated CA 19-9 serum level. Furthermore, elevated serum CA 19-9 was also reported in simple or haemorrhagic CLC [41,42]. Serum tumour markers cannot, therefore, be used as diagnostic tools for MHCN. Cystic fluid analysis, helpful in MHCN diagnosis, cannot discriminate benign and malignant MHCN. Our series’ intracystic tumour markers were indeed mostly elevated, irrespective of malignancy [5,43,44]. However, high intracystic CA 19-9 is also described in CLC and polycystic liver diseases [45–47]. Thus, nor CEA neither CA19-9 can help discriminate MHCN from other hepatic cystic lesions. Interestingly, Fuks et al. reported tumour-associated glycoprotein (TAG) 72 as a marker with high sensitivity and high specificity for the diagnosis of mucinous cysts as it is not expressed by normal biliary cells as opposed to CA19-9 and CEA. Percutaneous measurement of TAG 72 is reported to be useful for preoperative diagnostic of MHCN [48]. False negatives of fine needle aspiration (FNA) cytology are frequent, FNA’s sensitivity for diagnosing malignant MHCN is reportedly 66% [7,29,49,50]. However, FNA could lead to needle tract dissemination or peritoneal carcinomatosis [51] and is therefore not usually recommended [7,32].
Site-specific conjugation allows modulation of click reaction stoichiometry for pretargeted SPECT imaging
Published in mAbs, 2018
Danielle Mandikian, Hanine Rafidi, Pragya Adhikari, Priya Venkatraman, Lidia Nazarova, Gabriel Fung, Isabel Figueroa, Gregory Z. Ferl, Sheila Ulufatu, Jason Ho, Cynthia McCaughey, Jeffrey Lau, Shang-Fan Yu, Saileta Prabhu, Jack Sadowsky, C. Andrew Boswell
Most pretargeting antibodies have targeted highly expressed, non-internalizing antigens such as A33, CA19.9, and tumor-associated glycoprotein 72 (TAG-72) glycoproteins.4,23,30 While these early imaging studies were successful, highly expressed non-internalizing targets only represent a fraction of clinically relevant oncology targets since many cell-surface cancer targets are internalizing. For instance, clinical imaging of human epidermal growth factor receptor 2 (HER2)-expressing tumors has been actively pursued via directly labeled antibodies,40,41 antibody fragments42 and affibodies43 in an effort to improve patient selection and response monitoring for HER2-targeted cancer therapies.44 Fewer examples exist in which internalizing targets have been pretargeted,20,39 likely due to risk of time-dependent cell surface depletion of TCO moieties available for click reaction through antibody-bound receptor internalization, thereby decreasing image contrast. For instance, use of enzyme-based approaches for pretargeted imaging as an alternative to IEDDA reactions was successful for a non-internalizing antigen (TAG-72), but not for an internalizing antigen (HER2).45 However, there is a recent interest in pretargeted imaging of internalizing targets such as HER2 despite these challenges.20,39