Molecular imaging has been widely used as a powerful tool in the diagnosis and treatment of cancer. Thus, we have developed a series of novel molecular probes for cancer imaging. In this presentation, we will discuss our recent progress in imaging of two cancer targets. On one hand, current cancer treatments rely heavily on chemotherapeutic agents to induce cytotoxic DNA damages and programmed cell death in cancer cells. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway results in formation of abasic or apurinic/apyrimidinic (AP) sites and inhibition of AP sites leads to significant reduction of drug resistance and enhancement of drug sensitivity. Thus, AP-site formation has been identified as an important biomarker in DNA-targeted chemotherapies. To date, we have developed positron-emitting [11C]methoxyamine for positron emission tomography (PET) that allows for quantification of AP sites in vivo. On the other hand, the mesenchymal-epithelial transition (MET) receptor plays prominent role in human tumorigenesis, tumor progression and metastasis. Overexpression or mutation of MET results in activation of oncogenic signaling pathways and leads to up-regulation of diverse tumor cell functions. For efficacy evaluation of various MET-targeted anticancer therapies currently under development, it is critical to develop an imaging tool that permits detection and quantification of MET expression in vivo. Here, we report the radiosynthesis and evaluation of a molecular imaging probe, [11C]SU11274, for quantification of MET receptors in human cancers in vivo. These studies demonstrated that [11C]methoxy amine and [11C]SU11274-PET can facilitate efficacy evaluation in the clinical development of cancer therapeutics.

Molecular probes for cancer imaging

241st National Meeting (2011)

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