Comparison of the radiotoxicity of the ^99mTc-labeled compounds ^99mTc-pertechnetate, ^99mTc-HMPAO and ^99mTc-MIBI

Abstract

Purpose: In addition to gamma radiation, ^99mTc 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 three ^99mTc-labeled radiopharmaceuticals with differences in the subcellular distribution.

Materials and methods: The intracellular radionuclide uptake and subcellular distribution of [^99mTc]-pertechnetate (^99mTc-pertechnetate), [^99mTc]Tc-hexamethyl-propylene-aminoxime (^99mTc-HMPAO) and [^99mTc]Tc-hexakis-2-methoxyisobutylisonitrile (^99mTc-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: ^99mTc-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than ^99mTc-pertechnetate or ^99mTc-MIBI. The colony-forming assay showed that ^99mTc-pertechnetate and ^99mTc-HMPAO caused a similar reduction in cell survival. ^99mTc-MIBI is less radiotoxic in terms of the estimated nucleus dose and induced the fewest number of γH2AX foci compared with the other ^99mTc-tracers, and ^99mTc-HMPAO induced a fewer number of γH2AX foci than ^99mTc-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 by ^99mTc-HMPAO.

Keywords:

• ^99mTc
• ^99mTc-HMPAO
• ^99mTc-MIBI
• Clonogenic survival
• γH2AX
• radiotoxicity

Acknowledgements

The authors would like to thank Christin Froschauer for her excellent technical assistance and Dr Liane Oehme for helpful discussion.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Funding information

This work was supported by the Deutsche Forschungsgemeinschaft [KO 1695 4/1].