Comparison of the radiotoxicity of the99mTc-labeled compounds99mTc-pertechnetate,99mTc-HMPAO and99mTc-MIBI.
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 three99mTc-labeled radiopharmaceuticals with differences in the subcellular distribution.



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.



99mTc-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than99mTc-pertechnetate or99mTc-MIBI. The colony-forming assay showed that99mTc-pertechnetate and99mTc-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 other99mTc-tracers, and99mTc-HMPAO induced a fewer number of γH2AX foci than99mTc-pertechnetate.



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 by99mTc-HMPAO.
a University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden , Department of Nuclear Medicine , Dresden , Germany.
Ute
U
Maucksch
a University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden , Department of Nuclear Medicine , Dresden , Germany.
Roswitha
R
Runge
a University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden , Department of Nuclear Medicine , Dresden , Germany.
Gerd
G
Wunderlich
a University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden , Department of Nuclear Medicine , Dresden , Germany.
Robert
R
Freudenberg
a University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden , Department of Nuclear Medicine , Dresden , Germany.
Anne
A
Naumann
a University Hospital/Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden , Department of Nuclear Medicine , Dresden , Germany.
Jörg
J
Kotzerke
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D007553:Isotope Labeling; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D051381:Rats; D013670:Sodium Pertechnetate Tc 99m / Q000493:pharmacokinetics / Q000627:therapeutic use; D017556:Technetium Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019690:Technetium Tc 99m Exametazime / Q000493:pharmacokinetics / Q000627:therapeutic use; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*
D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D019690:Technetium Tc 99m Exametazime; D017256:Technetium Tc 99m Sestamibi; D013670:Sodium Pertechnetate Tc 99m
99mTc; 99mTc-HMPAO; 99mTc-MIBI; Clonogenic survival; radiotoxicity; γH2AX