1. 18F–FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6 inhibitor combination therapy in a murine model of human melanoma
- Author
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Ralf S. Eschbach, Philipp M. Kazmierczak, Maurice M. Heimer, Andrei Todica, Heidrun Hirner-Eppeneder, Moritz J. Schneider, Georg Keinrath, Olga Solyanik, Jessica Olivier, Wolfgang G. Kunz, Maximilian F. Reiser, Peter Bartenstein, Jens Ricke, and Clemens C. Cyran
- Subjects
Melanoma ,BRAF inhibitor ,CDK inhibitor ,18F–FDG-PET ,Diffusion-weighted MRI ,Therapy monitoring ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by 18F–FDG-PET/CT and diffusion-weighted MRI (DW-MRI). Methods Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18F–FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq 18F–FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density – CD31; tumor cell proliferation – Ki-67). Results Tumor glucose uptake was significantly suppressed under therapy (∆TTLTherapy − 1.00 ± 0.53 vs. ∆TTLControl 0.85 ± 1.21; p
- Published
- 2018
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