Preclinical evaluation of new PET tracer targeting L- type Amino Acid Transporter 1(LAT1): F-18 NKO-035 PET in inflammation model of rats

Objectives: L-type amino acid transporter 1 (LAT1) is overexpressed specifically in tumor cells with minimal expression in the normal tissues. LAT1 selective PET tracer is focusing attention as not only for the diagnosis in oncology but also monitoring of therapeutic effect in the LAT1-targeting therapies. Our group recently succeeded in the synthesis of the new PET tracer of ¹⁸F-NKO035 with high synthetic yield and high specific activity. The purpose of this study was to evaluate the whole body distribution of ¹⁸F-NKO035 using the rat inflammation models. [Methods]Wistar rats were purchased from Japan SLC Inc (n=6, body weight=190.2±4.1g). The rat model of inflammation was established by bilateral subcutaneous injection of turpentine oil (0.2ml). On day 4 after injection of the oil, static PET scans were performed 1 hour after intravenous injection of ¹⁸F-NKO035 (53.9±1.5MBq) and dynamic PET scan was performed in one rat. Volumes of interest were placed on the lesions using PMOD (ver3.6) and uptake in the inflammatory lesions were analyzed. After the PET scan, rats were sacrificed. Blood sample were analyzed to verify stability of NKO035 as chemical compound and metabolite analysis. Hematoxylin and eosin staining of the inflammatory lesions were performed for histopathological evaluation. [Results]Time activity curve and static PET scan showed low accumulation of NKO035 in inflammatory lesions (SUV_max at 60min =1.50 ± 0.20). Among normal organs, physiological accumulation on the bilateral kidneys (SUV_mean at 60min =5.64 ± 0.48) and the pancreas (SUV_mean at 60min =1.87 ± 0.19) were observed. Metabolite analysis indicated that about 90% of NKO035 remain unchanged in vivo at 75min post injection. H&E staining showed inflammatory reactions such as aggregation of neutrophils and macrophages as well as formation of granulation at the site of turpentine injection. [Conclusions] This study showed the utility of ¹⁸F-NKO035 as LAT1 specific probe with low accumulation in the inflammatory lesions, suggesting the feasibility of tumor specific PET imaging. Further study is warranted to confirm the high uptakes in the tumors with high LAT1 expression for the theragnostics targeting LAT1 .

• Download figure
• Open in new tab
• Download powerpoint