Assessment of 11C-2-Aminoisobutyric Acid in Nude Mice with Tumor and Inflammation

Objectives: 18F-fluoro-deoxy-D-glucose (FDG) highly accumulates in tumors and is widely used for cancer diagnosis. However, 18F-FDG also accumulates in therapy-induced inflammatory changes within tumors. We, therefore, need a new PET tracer that selectively accumulates in viable tumor cells but not in inflammatory cells for more precise diagnosis of therapy response. 2-Aminoisobutyric Acid (AIB) is a non-metabolized analog of alanine and a substrate of system A. Since system A is an unidirectional amino acid transporter, AIB is directly concentrated in cells. Although several studies showed that 11C-AIB highly accumulated in tumors in animal models and in patients, the synthesis methods used in those studies are not suitable to use for a routine production. Recently, we developed a simple and efficient synthesis method [1] applicable for a routine use. To assess whether 11C-AIB is useful for therapy response diagnosis or not, we evaluated tumor and inflammation uptake of 11C-AIB compared with that of 18F-FDG using biodistribution and small animal PET experiments in a animal model having both tumor and inflammation.Methods: BALB/c-nu/nu male mice were subcutaneously inoculated with small cell lung cancer SY cells in right lower flank region. At 24 to 30 h before experiments, turpentine was intramuscularly injected into left hind leg. For biodistribution study, at 15, 30, 60 and 90 min after intravenous (i.v.) injection of 11C-AIB, or 30 and 60 min after i.v. injection of 18F-FDG, blood and major organs were removed and weighted, and the radioactivity was measured. For PET experiment, we first conducted PET imaging with 11C-AIB and, 6 h later, 18F-FDG PET in the same mouse. Serial PET data were acquired for 60 min after i.v. injection of each tracer. Tracer uptake was semi-quantified as standardized uptake value (SUV).Results: Biodistribution and PET experiments showed that tumor uptake of 11C-AIB increased with time and was higher than that of 18F-FDG. SUVmax of tumors of 11C-AIB and 18F-FDG were 3.03+-0.51 and 1.6+-0.24 at 50-60 min, respectively. In contrast, the uptake in inflamed sites of 11C-AIB was lower than that of 18F-FDG. SUVmax of inflamed sites of 11C-AIB and 18F-FDG were 0.7+-0.10 at 3-4 min and 1.14+-0.06 at 50-60 min, respectively. Tumor-to-inflamed site ratio of 11C-AIB was higher than that of 18F-FDG, while inflamed site-to-muscle ratio of 11C-AIB was lower than that of 18F-FDG.19th International Symposium on Radiopharmaceutical Sciences, the ISRS 2011