Accumulation and transport mechanism of anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid in representative human carcinomas

Objectives Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid ([¹⁸F]FACBC) is a promising radiotracer for in-vivo imaging human glioblastoma and prostate carcinoma. However, there are no reports for detecting other carcinomas using [¹⁸F]FACBC. We examined accumulation and transport mechanism of [¹⁸F]FACBC in representative human-derived carcinoma cells and compared with [¹⁸F]FDG.

Methods The [1-¹⁴C]FACBC or [¹⁴C]FDG were added in five types of cultured human carcinoma cells (epidermal carcinoma: A431, colorectal carcinoma: LS180, lung carcinoma: PC14/GL, H441/GL, breast carcinoma: MDA-MB435) with and without a specific Na⁺-dependent system A inhibitor (MeAIB) and Na⁺-independent system L inhibitor (BCH). The radioactivity in the cells was measured at incubation time of 0.5, 1, 3, 10 min. The accumulation of [1-¹⁴C]FACBC was compared with that of [¹⁴C]FDG. The transport mechanism of [1-¹⁴C]FACBC was investigated using gene analysis of DNA microarray and real-time polymerase chain reaction method.

Results The accumulation of [1-¹⁴C]FACBC in the A431 and PC14 gradually increased over time, while the LS180, H441 and MDA-MB435 reached peak at incubation time of 3 min and then decreased. From results of gene analysis, the main transport in the A431 and PC14 was through both system A and system L, and the LS180, H441 and MDA-MB435 was through only system L. On the other hand, the accumulation of [¹⁴C]FDG lineally increased in all carcinoma cells. The values of [1-¹⁴C]FACBC at 3 min was 1.6-4.7 times higher than those of [¹⁴C]FDG.

Conclusions [¹⁸F]FACBC will be useful radiotracer for diagnosing the human carcinomas by means of accumulation change depending on expression level of system A and/or system L in the carcinomas even if there are little differences of [¹⁸F]FDG accumulation in the carcinomas