Contemporary radiopharmacy has played a significant role in the development of early oncological diagnostics. Such radiopharmaceutics as 18F-FMISO, 123I-IAZA, 99m Tc-HL-91 (Fig. 1b, 3b, 7b) are used in the state-of-the art scintigraphic and tomographic techniques, i.e. in the PET and SPECT methods to determine carcinoma progression and detect cells in hipoxic state already at the early stage of carcinoma development [2, 3]. These noninvasive and selective for hipoxic cells methods are characterized by excellent sensitivity and do not exert noxious effect on the remaining cells of the human organism [4, 5]. Characteristic hipoxia of solid tumors can be also identified with invasive methods, e.g. Elisa test or measurement of oxygen concentration in pathological cells using a microprobe. However, medical interference in the tissues affects the condition of the whole organism. Technical complications and low accuracy resulting from non-uniform hipoxia of the cancerous tissue environment render rear usage of these methods in clinical practice [3]. Diagnosis of hipoxia occurring in the carcinoma-changed cells permits treatment with drugs possessing bioreductive mechanism of activity. In this group of drugs, apart from nitro compounds and chinon derivatives, we can distinguish compounds with N-oxide structure [25]. Tripazamine (Fig. 11b) and banoxantrone (Fig. 11a) represent the latter group of compounds. These are so far the drugs with the best therapeutic parameters expressed by selectivity, efficiency of action and low general toxicity [25]. Also, gene therapy with the use of adenovirus vector coding nitroreductase seems to be a promising mode of treatment. This enzyme induces cytotoxic activity of nitro compounds, e.g. CB1954 (Fig. 10c), for cancerous cells with hypoxia [26].
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Cancer chemotherapy over twenty years has been under extremely intensive investigation. Failure in the treatment of neoplasms is due to characteristic fe-atures of cancer cells. Their structure delays and decreases the efficacy of drugs administered orally or intravenously. Therefore, greater emphasis is placed on the development of new molecular studies. The development of particular molecular diagnostic methods is based on new advances in immunology, genetics and nuclear medicine. Nuclear medicine concentrates on the diagnostics and treatment of various diseases, including neoplasms treated by means of radiopharmaceuticals. The isotope most commonly used as a source of g radiation for radiopharma-ceuticals is technetium (99mTc). The complexes of this radiotracer (e.g. 99mTc-HM-PAO, 99mTc-CB-PAO, 99mTc-ECD) are widely used for brain imaging. These compounds indicate areas of normal blood supply in the brain, but do not enter hypoxic tumour cells. The differences in oxygenation level between normal and cancer cells is key strategy used not only in the diagnostics, but also in the treatment of neoplasms. Some compounds [quinone antibiotics,nitroimidazoles, tirapazamine] are known as hypoxia selective agents activated in low oxygen concentrations. Another strategy used in anticancer therapy aims at the inhibition of angiogenesis in the tumour; other methods limit the growth of tumour - these include use of inhibitory enzymes such as telomerase inhibitors (phosphorothioate oligonucleotides, cisplatin) and polyamine metabolism inhibitors (DFMO, MGBG). Valuable antineoplastic drugs originate from natural sources. Currently, the derivatives of acronycine and spongiostatin are being investigated. Natural compounds with a documented anticancer activity include, for example, taxol , etopozide and tenipozide. New directions in the research of new compounds for use in the diagnostics and treatment of neoplastic diseases are closely related to the development of molecular studies, which offer explanation of complex patophysiology of tumours on molecular level. Also. medical chemistry plays an important role in modern investigation methods, such as molecular modelling.
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