Pharmacokinetic Evaluation of [11C]CEP-32496 in Nude Mice Bearing BRAFV600E Mutation-Induced Melanomas.

摘要: CEP-32496, also known as RXDX-105 or Agerafenib, is a new orally active inhibitor for the mutated v-raf murine sarcoma viral oncogene homolog B1 (BRAFV600E), which has attracted considerable attention in clinical trials treatment of human cancers. Here, we used carbon-11-labeled CEP-32496 ([11C]CEP-32496) positron emission tomography (PET) radiotracer to evaluate its pharmacokinetic properties and explore potential vivo imaging. Following synthesis, performed vitro binding assays autoradiography [11C]CEP-32496 A375 melanoma cell line on tumor tissue sections from mice harboring BRAFV600E mutation. These were followed by PET scans biodistribution studies nude bearing subcutaneous cell-induced melanoma. showed high affinity BRAFV600E-positive cells densely accumulated respective sections; this could be blocked selective antagonist sorafenib unlabeled CEP-32496. The results revealed that continuously but slowly into within period 0 60 minutes postinjection A375-melanoma-bearing mice. Metabolite analysis stability plasma. Our indicate excellent specificity mutation vitro, while noninvasive personalized diagnostic role needs studied further.