11C-Labeled 1,7β,10β-trihydroxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate 13-{(2 R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate}

Excerpt

Docetaxel is a diterpine (taxane) anti-mitotic agent that binds to free tubulin and leads to the assembly of stabilized microtubule bundles, inhibition of the cell cycle, and cell death due to apoptosis (1). This drug has been approved by the United States Food and Drug Administration as a single-agent treatment of metastatic breast cancer, metastatic androgen-independent prostate cancer, and advanced non-small cell lung cancer (NSCLC), and as an adjuvant in combination with doxorubicin and cyclophosphamide for the treatment of early-stage breast cancer (2). Patients treated with docetaxel often experience drug-related toxicity (due to myelosuppression) and show limited or no response to the treatment (3). To some extent, the response to an anti-neoplastic drug, including docetaxel, depends on attaining a sufficiently high concentration in the cancerous lesions, so it is important to quantify the uptake of an anti-cancer agent by the affected tissues to assess the efficacy of a drug. Therefore, measuring the amount of radionuclide-labeled docetaxel that has accumulated in cancerous tumors can be of prognostic value to predict patient response to the treatment (4). For this, ¹¹C-labeled docetaxel ([¹¹C]-docetaxel) was synthesized (5), and in a preliminary study its biodistribution was investigated in normal rats (4). In another study, the biodistribution and radio-dosimetry of [¹¹C]-docetaxel was investigated in cancer patients (6), and recently the kinetics of [¹¹C]-docetaxel was studied using positron emission tomography (PET) in lung cancer patients (3).