There is a high demand for a tumor specific imaging, staging and therapy monitoring by PET. Currently, FDG (2-[F-18]fluoro-2-deoxyglucose) is the commonly used agent for tumor detection and staging. However, this method cannot differentiate between tumor and inflammatory lesions. In addition, FDG does not accumulate in tumors with low glycolytic activities, such as prostate cancer. It is not optimal for specific detection of brain tumors and metastases due to a high background signal resulting from healthy brain metabolism. The amino acids L-glutamine and L-glutamate as well as their corresponding transporters play a key role in the adapted intermediary metabolism of tumors. We synthesized and evaluated a new PET imaging agent BAY 94-9392, a derivative of L-glutamate. This agent was successfully used for tumor detection with high sensitivity and specificity as demonstrated in various preclinical models.

Methods: The radiosynthesis of (4S)-4-(3-[F-18]fluoropropyl)-L-glutamate (BAY 94-9392) was established on a commercial synthesis module. BAY 94-9392 was investigated in a variety of tumor cell lines as well as tumor models for uptake, biodistribution, mode of action, and its potential to differentiate between tumor versus inflammation.

Results: BAY 94-9392 is specifically transported by the cystine/glutamate exchanger (xCT, SLC7A11) and it is not metabolized. Compared to FDG, the agent displayed a high accumulation rate in a panel of tumor cells. PET imaging with excellent tumor visualization and high tumor to background ratios was achieved in a variety of preclinical tumor models. BAY 94-9392 did not accumulate in inflammatory lesions, whereas FDG shows a strong uptake in this turpentine oil induced and histopathologically confirmed rat model.

Conclusions: BAY 94-9392 is a new, promising tumor specific PET tracer. Both preclinical and clinical studies are in progress for further characterization.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2800. doi:10.1158/1538-7445.AM2011-2800