Antibodies (Abs) are glycoproteins secreted from plasma B cell and are used by immune system to identify and remove foreign pathogens such as bacteria and viruses. Because it is considered that Abs also have cytotoxic potency against some malignant tumor cells, the therapeutic efficacy in cancer has been examined. However, intact Abs are insufficient to improve patient survival rate dramatically. As a one approach to enhance the therapeutic response by using immunological technique, cytotoxic radioisotopes (- or -particle emitters) are conjugated to Abs or the fragments. This strategy is employed to deliver radioisotopes to the targeting tissue by appropriate vehicle. After the radiolabeled Abs bind to receptors/tumor antigens expressed on the surface of cancerous tissue, cells within an anatomic region of the - or -range will be killed.

In a clinical field, systemic radiotherapy using naked radioisotope was first performed by Hertz to patient of Graves’ disease in 1941. Then, investigations on the use of Abs coupled with adequate radioisotopes subsequently emerged in the early 1950s. Though direct radioiodinated Abs were mainly used in the initial clinical studies, progress in chelation chemistry has enabled the utilization of many therapeutic metal radioisotopes that possess inherent radiation properties. Various combinations of Abs and radioisotopes have been examined, which results in the adaptation in different clinical situations. RIT involves the application of radiolabeled monoclonal Abs (mAbs) to molecular targeted therapy. Both the use of directly labeled mAbs and in vivo label of tumor-binding mAbs by conjugation-pretargeting method have been developed.

Irradiated cells absorb high amounts of energy in the form of photons or charged particles, which promote the direct macromolecular damage as well as the generation of reactive oxygen and/or nitrogen species. Both free radicals and molecular oxygen damage DNA strand and the damage induces not only apoptosis but also programmed necrosis. Because the ranges in tissue of ionizing radiations are rather large compared with a typical cell size, uniform binding of the radioimmunoconjugates is not a prerequisite for its efficacy. In other words, adjacent cells not expressing the receptors/tumor antigens can also be killed by the physical cross-fire effect. This means continuous low-dose irradiation from radiolabeled Abs cause lethal effects on nearby normal cells. Moreover, it is reported that RITs also evoke the normalization of tumor vasculature, presumably owing to facilitation of immune cell migration towards the malignant lesions .

For therapy, therefore, - or -particle emitters are preferable. Vehicles coupled with radioisotopes emitting Auger electrons are also available; however, they need to be localized close to DNA due to the very short range of these radiations. Simultaneous emission of γ (X) rays, which are suitable for imaging, will help measure pharmacokinetic parameters and calculate dosimetry of the radioimmunoconjugates. Table 1 shows radioisotopes commonly used for RIT.The article submission is accepted through an online submission system as well as email at radiology@scholarlypub.com or Submit online

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