Targeting of
tumor cells with radiolabeled biomolecules is a possible approach to inactivate disseminated
tumor cells. However, rapid degradation of the biomolecules after cellular internalization and subsequent excretion of the radioactivity is a problem. We studied the possibility of using
dextran as a carrier of
radionuclides to improve the intracellular retention. An
EGF-dextran conjugate, aimed for targeting of
tumor cells overexpressing the
EGF-receptor, was used as model. Retention tests were performed with (125)I on different parts: [(125)I]-
EGF-
dextran-[(125)I], [(125)I]-
EGF-
dextran and
EGF-
dextran-[(125)I]. Comparisons were made with [(125)I]-
EGF. The radiolabeled compounds were incubated with cultured
glioma cells for different times. The cellular retention of radioactivity was then measured for up to 24 h. Expected radiation doses at the cellular level were calculated assuming that (131)I, instead of (125)I, was coupled to
EGF and
EGF-
dextran. The results indicated that the
EGF-part of the conjugate was degraded and the
EGF-attached radioactivity was rapidly excreted, whereas radioactivity on
dextran was retained intracellularly to a high degree, i.e. 70-80% of the radioactivity bound to
dextran was still cell-associated after 24 h. The retention after 24 h was significantly higher (p < 0.001) when the radioactivity was on the
dextran instead of the
EGF-part. The radiolabeled
EGF-
dextran had a notably high specific radioactivity; up to 11 MBq/microg. There was potential for at least hundred times increased radiation dose per receptor interaction when the radioactivity was on the
dextran part. The advantage with radioactivity on the
dextran part was the high cellular retention and the high specific radioactivity (higher than previously reported for other residualizing labels) without severe loss of receptor specific binding. Thus,
dextran seems suitable as a carrier of
radionuclides aimed for
therapy and gives potential for a highly increased radiation dose.