Monitoring mitochondrial metabolisms in irradiated human cancer cells with (99m)Tc-MIBI.

Cationic hexakis(2-methoxyisobutylisonitrile)-technetium-99m ((99m)Tc-MIBI), an agent for scintigraphic detection and imaging of tumors, accumulates in mitochondria of various cells and tissues of high mitochondrial metabolic activity. To monitor the mitochondrial metabolisms of human cancer cells exposed to ionizing radiation, uptake of (99m)Tc-MIBI in an irradiated human lung cancer cell line (A549) was measured at 1-12 h following 0-9 Gy irradiation in vitro. Mitochondrial membrane potential, an index of mitochondrial activity, was also determined by flow cytometry with 3,3'-dihexyloxacarbocyanine (DiOC6(3)). At 1 h after 3 and 9 Gy irradiation, cellular (99m)Tc-MIBI accumulation increased by 10.5 +/- 1.6 and 16.8 +/- 5.6% compared with controls, respectively (P < 0.01) DiOC6(3) measurement also showed increased mitochondrial membrane potentials immediately after irradiation, consistent with (99m)Tc-MIBI changes. The present findings showed that the transient hyperactivated mitochondrial metabolism and subsequently decreased activities following irradiation were monitored by determining the cellular (99m)Tc-MIBI accumulation, suggesting the possibility of (99m)Tc-MIBI scintigraphy as a functional imaging to monitor tumor metabolisms after radiation therapy.