Beitrag zum Verständnis der biologischen Wirksamkeit des Auger-Elektronen emittierenden Radionuklids I-125 in menschlichen Zellen
The Auger-electron-emitter I-125 was positioned in different compartments of human cells by the use of three carrier molecules (I-125-iododeoxyuridine for DNA-incorporation, I-125-antipyrine for distribution throughout the whole cell, and NaI-125 for extracellular positioning) and the effects were compared with those of Cs-137-gamma-radiation. With regard to a clinical application in the adjuvant radio- therapy of tumors, all experiments were carried out under physiological conditions. The two dominant biological end- points were clonogenic survival and molecular DNA damage measured by the alkaline comet assay. In a comparison of the carrier molecules I-125-UdR demonstrated the most radiotoxic effect whereas I-125- antipyrine was obviously less effective. NaI-125 hardly produced any biological effect. The declining radiotoxicity of the I-125-labeled carrier molecules was explained by the increasing distance of the I-125 decay site from the DNA. A strong correlation was found between increasing DNA damage and reduced colony-forming ability. The biological effects of I-125 were compared with those of the reference radiation Cs-137-gamma, but only for I-125- antipyrine, which distributed its energy nearly homogeneously throughout the cell, was a dose calculation possible. A quantitative assessment of the biological efficacy for I-125-UdR was made for the first time by efficacy factors focusing on a definite endpoint. Efficacy factors of 24 - 28 were found for I-125-UdR relative to the 37%-surviving fraction and compared with Cs-137-gamma- radiation.
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