Abstract
Functional imaging using S-[methyl-11C]methionine (11C-Met) provides earlier estimation of tumor response after therapy compared to anatomical methods. However, cyclotron facilities are required to produce and use 11C-Met, due to its short half-life (20 min). Since intracellular energy-dependent transmethylation would be involved in tumor accumulation of 11C-Met, development of 18F (T1/2: 110 min) or 123I (T1/2: 13 h)-labeled radiopharmaceuticals affording diagnosis information similar to that of 11C-Met has been hampered. In this study, to find out the cellular functions that provide diagnosis information similar to energy-dependent transmethylation of 11C-Met, we evaluated the energy-dependent amino acid transport system A, using its specific substrate,
[14C] α-(methylamino) isobutyric acid (14C-MeAIB). The carbon ion beam irradiation (3Gy) reduced the uptake of both 14C-MeAIB and 14C-Met to HSG human salivary gland tumor cells. The decrease in the uptake of both 14C-MeAIB and 14C-Met to the tumor cells proceeded in advance of the decrease in cell number and intracellular net ATP levels. The decreased uptake of 14C-MeAIB to carbon ion beam irradiated-HSG cells was caused by the decrease in amino acid transport system A-mediated uptake. These results indicated that the amino acid transport system A would constitute a sensitive target to predict therapeutic efficacies of tumor therapy.
