Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033

摘要: This study was designed as “proof of concept” for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses molecularly targeted therapy. Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6–8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 6 7) [18F]fluorodeoxyglucose, [18F]fluoro-L-thymidine, [18F]fluoro-azoazomycinarabinoside [18F]fluoromisonidazole. Separate cohorts (n=3) identically tumours assessed ex vivo markers glucose metabolism, proliferation hypoxia. During period, mean uptake all tracers generally increased control compared baseline. In contrast, tracer into CI-1033-treated decreased by 20–60% during treatment. Expression transporter Glut-1 cell cycle unchanged in treatment, Thymidine kinase activity reduced baseline at day but sevenfold higher versus Uptake hypoxia marker pimonidazole stable severely following 7 days treatment significantly affects determined PET. The findings correlated well biomarkers each cellular processes studied. These results confirm utility evaluation effectiveness therapies simultaneously definition specific involved therapeutic response.