Therapy response monitoring of the early effects of a new BRAF inhibitor on melanoma xenograft in mice: evaluation of 18F‐FDG‐PET and 18F‐FLT‐PET

In this study we investigated the feasibility of 18F‐FDG and 18F‐FLT‐PET to monitor the early effects of the BRAFV600E inhibitor in mice with melanoma xenografts. SCID/beige mice with subcutaneous (s.c.) A375 melanoma xenografts, expressing BRAFV600E, received the BRAFV600E inhibitor twice daily orally (0, 25, 50 and 75 mg/kg). At 1, 3 and 7 days after start of therapy, the uptake of 18F‐FDG and 18F‐FLT in the tumor and normal tissues was determined in ex vivo tissue samples. Serial 18F‐FDG and 18F‐FLT‐PET scans were acquired of animals at 1 day before and 1, 3 and 7 days after start of treatment with 75 mg/kg BRAFV600E inhibitor. A dose‐dependent decrease in 18F‐FDG uptake in the A375 tumors was observed by ex vivo biodistribution analysis. Administration of 75 mg/kg BRAF inhibitor for 1, 3 and 7 days resulted in a significantly decreased 18F‐FDG uptake in A375 tumors (41, 35 and 51%, respectively). 18F‐FLT uptake in the A375 tumors was low at baseline and no significant changes in 18F‐FLT uptake were observed at any of the doses administered. These effects were corroborated by serial in vivo 18F‐FDG and 18F‐FLT‐PET imaging. These data demonstrate that 18F‐FDG‐PET can be used as an imaging biomarker to noninvasively evaluate the early effects of PLX3603. Copyright © 2014 John Wiley & Sons, Ltd. In this study the feasibility of 18F‐FDG and 18F‐FLT‐PET to monitor the early effects of PLX3603, a new BRAFV600E inhibito...
Source: Contrast Media and Molecular Imaging - Category: Radiology Authors: Tags: Full Paper Source Type: research