Labeling of mixed leukocytes with (99m)Tc-HMPAO causes severe chromosomal aberrations in lymphocytes.

UNLABELLED: 99mTc-d,1-hexamethylpropyleneamine oxime (HMPAO) is widely used as a labeling agent for leukocytes in the diagnosis of inflammatory or infectious foci. Cytotoxicity studies have indicated that intracellular labeling of leukocytes with (111)In compounds may have severe detrimental effects on the cells. METHODS: In this study, the radiotoxic effects on mixed lymphocytes after labeling with (99m)Tc-HMPAO was investigated using the cytokinesis-blocked micronucleus assay and chromosomal aberration assay. RESULTS: Whereas negligible numbers of chromosome abnormalities were noted in unlabeled lymphocytes, the labeled lymphocytes showed multiple aberrations of various types, including dicentric, tricentric, and fivecentric chromosomes; centric rings; chromosome and chromatid type breaks; and acentric fragments. CONCLUSION: Heavily aberrant lymphocytes are seen in (99m)Tc-HMPAO-labeled mixed leukocytes after routine clinical procedures. It is unlikely, however, that this would cause detrimental effects, such as lymphoid malignancy, as these cells would normally be eliminated through apoptosis or phagocytosis.

Assessment of radiation-induced DNA damage caused by the incorporation of 99mTc-radiopharmaceuticals in murine lymphocytes using single cell gel electrophoresis.

The DNA damage induced by the 99mTc-radiopharmaceuticals incorporation to the cell was determined by the single-cell gel electrophoresis in murine lymphocytes in vitro. The 99mTc-hexamethyl-propylene amine oxime (99mTc-HMPAO) and 99mTc-2, 5-dihydroxybenzoic acid (99mTc-gentisic acid) induced nearly 100% of cells with breaks and/or alkali labile sites, which is explained by the action of the Auger electrons produced by the decay of the 99mTc. These results agree with the doses of 1.6 and 1.0 Gy estimated by subcellular dosimetry for 99mTc-HMPAO that is incorporated in the cytoplasm, and the 99mTc-gentisic acid, which remains bonded to the cell membrane, respectively. The results imply that Auger electrons are able to cause important DNA damage, when the radionuclide is incorporated in the range of a few microns from the nuclei.