Diagnosis of bladder cancer using ¹⁸F-labeled α-methyl-phenylalanine tracers in a mouse model

Although 2-¹⁸F-fluoro-2-deoxy-glucose (¹⁸F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of primary/recurrent lesions in the bladder, mainly because of interference by the pooled radioactivity in the urine. Our previous study revealed promising properties of L- and D-2-¹⁸F-α-methyl-phenylalanine (2-¹⁸F-FAMP) as radiotracers; i.e., their rapid blood clearance and low renal accumulation. In the present study we evaluated the utility of L- and D-2-¹⁸F-FAMP for imaging bladder cancer in a mouse model.

We used the human bladder cancer cell line HT1376 to prepare a bladder cancer xenograft model in mice bearing both orthotopic and subcutaneous tumors. Biodistribution and PET imaging studies were performed at 1 and 3 h after injection of L-2-¹⁸F-FAMP or D-2-¹⁸F-FAMP. ¹⁸F-FDG was used as a control.

At 1 h after injection, greater accumulations of both L-2-¹⁸F-FAMP and D-2-¹⁸F-FAMP were observed in the orthotopic tumors compared to ¹⁸F-FDG. The orthotopic tumor-to-muscle ratio of D-2-¹⁸F-FAMP was significantly higher than that of ¹⁸F-FDG (p < 0.01), because of the rapid blood clearance of D-2-¹⁸F-FAMP. L-2-¹⁸F-FAMP showed the highest subcutaneous tumor-to-muscle ratio (p < 0.01) due to its high subcutaneous tumor uptake. Compared to L-2-¹⁸F-FAMP, D-2-¹⁸F-FAMP exhibited faster clearance and lower kidney accumulation. In the PET imaging studies, L- and D-2-¹⁸F-FAMP both clearly visualized the orthotopic bladder tumors at 1 h after injection.

Our study showed that L-2-¹⁸F-FAMP and D-2-¹⁸F-FAMP have the potential to detect bladder cancer.