Preclinical Study of 18F-ML-10 to Evaluate Early Target Therapy Response of Novel MDM2-p53 Antagonist APG115 in Dedifferentiated Papillary Thyroid Carcinoma: A Comparison with 18F-FDG PET

1130 Purpose: Molecular imaging of cell apoptosis may detect the cellular response to novel target therapies and determine treatment efficacy early on, assisting in the design of individualized therapy. 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) PET/CT imaging, as lately developed molecular imaging of cell apoptosis, can selectively target cells undergoing apoptosis. Previous study has reported that novel MDM2-p53 antagonist APG115 could induced cell apoptosis in dedifferentiated papillary thyroid carcinoma(DePTC). Hereby, we compared the predictive ability of cell apoptosis imaging using 18F-ML-10 with the current gold standard 18F-FDG for treatment response assessment after targeted therapy with this novel antagonist. Methods: Early targeted therapy response evaluation was investigated by 18F-ML-10 and 18F-FDG PET imaging in treatment-sensitive TPC-1 and treatment-resistant B-CPAP human DePTC xenografts 48 h after a single increasing doses of APG115 or vehicle control. Radiotracer uptake was counted ex vivo by γ-counting and autoradiography and compared with Z-DEVD-aminoluciferin bioluminescent imaging of activated caspase-3/7 and DNA fragmentation (TdT-mediated dUTP nick-end labeling [TUNEL]). Results: TPC-1 subcutaneous xenograft tumors uptake of 18F-ML-10 were dose-dependent augmented from baseline in vehicle-treated control mice (P