Potential genotoxic effect of 186Re-HEDP on human lymphocyte cells: in-vitro evaluation with micronucleus-FISH...

Systemic and local therapies can be used to treat painful bone metastases. It has been shown that certain pharmaceuticals such as 186Re (rhenium-186) are effective in the treatment of pains caused by bone metastasis and a correlation between bone metastases and T cells has also been shown. The aim of this study was to investigate the genotoxic effect of 186Re-1,1-hydroxyethylidenediphosphonate (186Re-HEDP) on the cultured peripheral blood lymphocytes using an micronucleus (MN)-fluorescence in-situ hybridization assay.

Two lymphocyte cultures, with and without 186Re-HEDP, were set up from 20 healthy individuals. MN frequencies were determined by a classical cytokinesis-blocked micronucleus assay and samples with the highest MN frequencies were used for fluorescent in-situ hybridization analyses with the 'all human centromeres' probe.

Our results show a significant increase in the MN frequency in 186Re-treated lymphocytes compared with the untreated group (P<0.001). The frequencies of centromere-positive [CEN(+)] and centromere-negative [CEN(-)] MN in the 186Re-treated and untreated groups were found to be similar; however, the ratio of CEN(-)/CEN(+) MN frequency was lower in 186Re-treated samples.

These preliminary results support the idea that 186Re-HEDP is a highly genotoxic radiopharmaceutical and shows a proaneugenic effect. Causing genotoxicity in lymphocytes, especially in T cells, that regulate bone metastases and tumor growth in bone, might be a mechanism of this pharmaceutical to reduce the pain of patients.