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Immunoscintigraphy and Radioimmunotherapy
Published in Siegfried Matzku, Rolf A. Stahel, Antibodies in Diagnosis and Therapy, 2019
This is the most extensively studied field in immunoscintigraphy. Various antibodies have been used, the most often directed against epitopes of CEA or the tumor associated glycoprotein-72 (TAG-72), generally labeled with Indium-111 or Technetium-99m. 1-131 was rapidly abandoned because of its low photon yield and unnecessary irradiation due to its beta emission, 1-123 was used in only a few studies because of its restricted availability and relatively high costs. In primary tumors the sensitivity and specificity of immunoscintigraphy with either antibody and radiolabel is usually high, in the order of more than 80%, but the diagnosis of primary tumors was never based on immunoscintigraphy. This method was exceptionally able to detect previously unknown distant disease, but these rare cases probably do not justify its routine use for staging. Adding peroperative probe techniques (radioimmunoguided surgery, RIGS) to immunoscintigraphy allowed to increase diagnostic efficiency (Prati et al., 1995).
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
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