Radiobiological effect of 99mTechnetium-MIBI in human peripheral blood lymphocytes:: Ex vivo study using micronucleus/FISH assay

Tc-99m-MIBI is currently used, for cardiac investigations, for parathyroid thyroid imaging and evaluation of various tumours. It has been demonstrated that Tc-99m-MIBI is specifically taken up by the human peripheral blood lymphocytes (HPBL), cells which are known to be highly radiosensitive. To evaluate the possible chromosomal damage induced on HPBL by their in vitro exposure to increasing activities of Tc-99m-MIBI and also to establish whether HPBL undergo apoptosis or necrosis after in vitro exposure to Tc-99m-MIBI. Blood from two healthy donors were irradiated, incubated in vitro with increasing activities of Tc-99m-MIBI corresponding to absorbed doses ranging from 1 mu Gy,100 mu Gy, 1 cGy, 10 cGy, 50 cGy to 1 Gy. The cytokinesis block micronucleus (MN) assay was used and the frequency of binucleated cells (BN) with MN (MNBN) was analyzed in cultured HPBL (in either the G0- or G1- and S1-phase of the cell cycle). The fluorescence in situ hybridization (FISH) with pancentromeric probes was also applied to study the MN regarding whole chromosomes or acentric fragments. Apoptosis induction by 0.1 Gy of Tc-99m-MIBI in HPBL was quantified using annexin-V test. The frequencies of MNBC were similar in control cultures and in HBPL cultures exposed to 1 mu Gy, 100 mu Gy and 1 cGy. However, they were significantly higher (P < 0.05 versus controls and lower doses) after one treatment exposure to 0.25 mCi of Tc-99m-MIBI (corresponding to 10 cGy) or more but the percentages of MNBN with 10 cGy, 50 cGy and 1 Gy did not differ significantly. The increase of MNBN was more pronounced (P < 0.05) for cells irradiated during G1 phase than for those irradiated during G0 or S1. Using FISH, 80-90% of the MN were centromere negative. Although small, the absolute number of MN positive for centromeric signal and presumably containing whole chromosomes increased with doses. There is a statistically significant (P=0.001 and 0.006) increase of both apoptotic cells and necrosis, respectively, as compared to control cells in two times studied (24 and 36 h). Chromosomic damages can thus be demonstrated in HPBL after in vitro exposure of blood to at least 0.25 mCi of Tc-99m-MIBI corresponding to one absorbed dose of 10 cGy, and for this dose, apoptosis and necrosis phenomenons were detected. (c) 2005 Elsevier Ireland Ltd. All rights reserved.