Antibodies in Nuclear Medicine
Radiolabeled antibodies in nuclear medicine may be used for therapy or diagnosis. Diagnostic antibodies may be monoclonal antibodies (mAbs), directed against a specific disease, or polyclonal antibodies, which are used largely as intravascular reference m
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12 Antibodies in Nuclear Medicine A. Michael Peters 1. Introduction Radiolabeled antibodies in nuclear medicine may be used for therapy or diagnosis. Diagnostic antibodies may be monoclonal antibodies (mAbs), directed against a specific disease, or polyclonal antibodies, which are used largely as intravascular reference markers or markers of vascular permeability in the imaging of inflammatory disease. 2. Diagnostic mAbs Monoclonal antibodies may be labeled with a range of radionuclides, the choice of which is influenced by the anticipated duration of the study. Monoclonal antibodies are generally of mouse origin and can be radiolabeled and administered as the whole antibody, divalent F(abv)2 fragment, or monovalent Fab fragment. Again, the choice to some extent depends on the intended application, although to promote antigen accessibility and reduce possible immunological effects, including the generation of human antimouse antibodies in the recipient, the smaller fragments tend to be favored. Because of the almost infinite range of antigens that can potentially be targeted with radiolabeled mAbs, there is a wide range of disease processes for which immuno-scintigraphy may be helpful. A useful way to approach mAbs for imaging is to categorize them according to antigen accessibility: thus, targeted antigens may be intravascular, extravascular extracellular, or intracellular or otherwise “hidden.”
2.1. Intravascular Diagnostic mAbs that target intravascular antigens have been radiolabeled for imaging blood cells, components of thrombus, and endothelial adhesion molecules. From: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
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2.1.1. Blood Cells Two of the three major diseases that kill humans—thrombosis and inflammation (the third being cancer)—share, as a central constituent process, the recruitment of blood cells, namely platelets and leukocytes, respectively. A major advance in nuclear medicine was the development of cell labeling in 1975 (1). It had been possible to label blood cells with radioactivity before then but only with feeble or non-gamma emitting radionuclides like 32P and 51Cr. The aim of incorporating an efficient gamma emitter into blood cells was to be able to image thrombosis and inflammation with the gamma camera. The two radionuclides in general use in blood cell labeling for imaging are 111In and 99mTc. The principle underpinning cell labeling is that lipophilic metalchelate complexes of 111In and 99mTc readily penetrate blood cells and become irreversibly bound. 111In can be complexed to hydroxyquinoline or tropolone, and 99mTc with hexamethylpropyleneamine oxime (HMPAO). These lipophilic complexes freely diifuse across the cell membrane: 111In then binds to intracellular proteins, whereas 99mTc-HMPAO is converted to a secondary complex that, because it is hydrophilic, is unable to penetrate the lipid cell membrane and is therefore trapped inside the cell. Because of
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