Fakten und Fiktionen der Klientenprofessionalisierung Eine kritische
Die Professionalisierung von Klientenunternehmen im Umgang mit Unternehmensberatern stellt mittlerweile ein nicht mehr hinterfragtes, äußerst positiv bewertetes Faktum dar. Mithilfe einer umfassenden qualitativen empirischen Analyse zeigt Nicole Jung jedo
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rgeted Radioimmunotherapy TOD W. SPEER Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, UW Hospital and Clinics, Madison, WI, USA
Synonyms Radioimmunotherapy (RIT); Systemic radiation therapy; Systemic targeted radionuclide therapy (STaRT); Unsealed source brachytherapy
Definition Targeted radioimmunotherapy (TRIT) is a form of anticancer therapy that uses a targeting construct (antibody, antibody fragment, affibody, aptamer, peptide, nanotechnology), attached to a radionuclide (covalent bond or chelate molecule), to deliver a systemic cytotoxic dose of radiation to malignant tissue, thus representing a form of unsealed source of systemic brachytherapy. Depending upon the type of targeting construct, the immune system may have a synergistic role in inducing cell death. Intact antibodies will typically recruit elements of the immune system
for cytotoxic activity (due to the Fc region of the antibody), in addition to the cell kill induced by the radionuclide. Smaller constructs, other than intact antibodies, must rely largely upon the cytotoxic power of various radionuclides to induce cell kill. The radiation delivered to the target site from TRIT is released in an exponentially decreasing low dose and low dose-rate manor. This is due to the physical half-life of the radionuclide combined with the biological half-life of the targeting construct (in combination, the effective half-life).
Background Dr. Paul Ehrlich initially proposed the basic concept of TRIT in 1898. Although the so-called “magic bullets” of the Ehrlich era were chemical substances that were proposed to have special affinities for pathogenic organisms, his idea has been extrapolated to the concept of therapeutic compounds that specifically target pathological processes, hence potentially sparing normal tissue. This is the concept of targeted therapy. In 1908, Dr. Ehrlich received the Nobel Prize for his endeavors. As testimony to the complexities of developing these efforts into a workable form of targeted anticancer therapy, it took nearly 50 years before the first successful reports of TRIT began to show promise, as documented in published series, treating Wagner osteogenic sarcoma and melanoma patients with polyclonal antibodies, covalently bonded to I-131. Initially, antibodies were difficult to produce and isolate. As a result, the next several decades witnessed the utilization of relatively nonspecific targeting agents such as amino acids, cholesterol
L.W. Brady, T.E. Yaeger (eds.), Encyclopedia of Radiation Oncology, DOI 10.1007/978-3-540-85516-3, # Springer-Verlag Berlin Heidelberg 2013
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compounds, and hormones. Regardless, the cytotoxic potential of radionuclides was quite evident. In 1975, the hybridoma technique for producing monoclonal antibodies was published. Physicians and researchers had the long-awaited means to consistently produce a carrier molecule, for selected radionuclides that could accurately target tumor antigens. The modern concept for targe
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