Comparison of the radiotoxicity of the 99m Tc-labeled compounds 99m Tc-pertechnetate, 99m Tc-HMPAO and 99m Tc-MIBI.

PURPOSE: In addition to gamma radiation,99m Tc emits low-energy Auger electrons with path-lengths of nanometers to micrometers that cannot be utilized for diagnostic procedures; however, they have frequently been discussed for therapeutic applications. We compared radiotoxicity of three99m Tc-labeled radiopharmaceuticals with differences in the subcellular distribution.

MATERIALS AND METHODS: The intracellular radionuclide uptake and subcellular distribution of [99m Tc]-pertechnetate (99m Tc-pertechnetate), [99m Tc]Tc-hexamethyl-propylene-aminoxime (99m Tc-HMPAO) and [99m Tc]Tc-hexakis-2-methoxyisobutylisonitrile (99m Tc-MIBI) were quantified in rat thyroid FRTL-5 cells. Radiotoxicity was compared using late phosphorylated histone H2AX (γH2AX) foci as a marker for unrepaired DNA double-strand breaks (DNA-DSB) and clonogenic cell survival.

RESULTS: 99m Tc-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than99m Tc-pertechnetate or99m Tc-MIBI. The colony-forming assay showed that99m Tc-pertechnetate and99m Tc-HMPAO caused a similar reduction in cell survival.99m Tc-MIBI is less radiotoxic in terms of the estimated nucleus dose and induced the fewest number of γH2AX foci compared with the other99m Tc-tracers, and99m Tc-HMPAO induced a fewer number of γH2AX foci than99m Tc-pertechnetate.

CONCLUSIONS: Our findings reveal that clonogenic cellular survival is not solely determined by the DNA-DSB response. This finding may suggest the involvement of extra-nuclear radiosensitive targets in cell inactivation. For example, the mitochondria or the cell membrane could be affected by99m Tc-HMPAO.