Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of ^99mTc versus ¹⁸⁸Re

Abstract

Purpose: Cellular radionuclide uptake increases the heterogeneity of absorbed dose to biological structures. Dose increase depends on uptake yield and emission characteristics of radioisotopes. We used an in vitro model to compare the impact of cellular uptake of ¹⁸⁸Re-perrhenate and ^99mTc-pertechnetate on cellular survival.

Materials and methods: Rat thyroid PC Cl3 cells in culture were incubated with ¹⁸⁸Re or ^99mTc in the presence or absence of perchlorate for 1 hour. Clonogenic cell survival was measured by colony formation. In addition, intracellular radionuclide uptake was quantified.

Results: Dose effect curves were established for ¹⁸⁸Re and ^99mTc for various extra- and intracellular distributions of the radioactivity. In the presence of perchlorate, no uptake of radionuclides was detected and ¹⁸⁸Re reduced cell survival more efficiently than ^99mTc. A₃₇, the activity that is necessary to yield 37% cell survival was 14 MBq/ml for ¹⁸⁸Re and 480 MBq/ml for ^99mTc. In the absence of perchlorate, both radionuclides showed similar uptakes; however, A₃₇ was reduced by 30% for the beta-emitter and by 95% for ^99mTc. The dose D₃₇ that yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides.

Conclusions: Uptake of ¹⁸⁸Re and ^99mTc decreased cell survival. Intracellular ^99mTc yielded a dose increase that was higher compared to ¹⁸⁸Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of ¹⁸⁸Re and ^99mTc. At doses higher than 5 Gy intracellular ^99mTc became less radiotoxic than ¹⁸⁸Re, probably due to a non-uniform lognormal radionuclide uptake.

Keywords::

• Clonogenic cell survival
• Auger emitters
• Radionuclides
• ¹⁸⁸Re
• ^99mTc
• PC Cl3

Acknowledgements

The authors would like to express their gratitude to Prof. L. E. Feinendegen for his helpful advices and proofreading the manuscript. Furthermore we would like to give thanks to Prof. R. W. Howell and to Dr. E. Pomplun for valuable discussion at 7^th Auger Symposium.

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