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1 2008

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Rola hipoksji w postepach w diagnostyce i terapii chorób nowotworowych

Błaszczak-Świątkiewicz K., Mikiciuk-Olasik E.

Wiadomości Chemiczne

2008

[Z] 62, 11-12

1065-1089

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].