[18F]FLT-PET imaging does not always "light up" proliferating tumor cells
Menée à l'aide de xénogreffes, cette étude analyse les facteurs susceptibles de modifier les images de prolifération tumorale réalisées à l'aide de la tomographie par émission de positrons au fluor 18
Purpose: [18F]FLT-PET imaging was proposed as a tool for measuring in vivo tumor cell proliferation. The aim of this report was to validate the use of [18F]FLT-PET imaging for measuring xenograft proliferation and subsequent monitoring of targeted therapy. Experimental design: In exponentially growing xenografts, factors that could impact the outcome of [18F]FLT-PET imaging, such as nucleoside transporters, thymidine kinase 1, the relative contribution of DNA salvage pathway and the ratio of FLT to thymidine, were evaluated. The [18F]FLT tracer avidity was compared with other proliferation markers. Results: In a panel of proliferating xenografts, [18F]FLT or [3H]thymidine tracer avidity failed to reflect the tumor growth rate across different tumor types, despite the high expressions of Ki67 and TK1. When FLT was injected at the same dose level as used in the preclinical [18F]FLT-PET imaging, the plasma exposure ratio of FLT to thymidine was approximately1:200. Thymidine levels in different tumor types appeared to be variable and exhibited an inverse relationship with the FLT tracer avidity. In contrast, high-dose administration of BrdU (50 mg/kg) yielded a plasma exposure more than 4-fold higher than thymidine, and leads to a strong correlation between the BrdU uptake and the tumor proliferation rate. In FLT tracer-avid models, [18F]FLT-PET imaging as a surrogate biomarker predicted the therapeutic response of CDK4/6 inhibitor PD-0332991. Conclusions: Tumor thymidine level is one of the factors that impact the correlation between [18F]FLT uptake and tumor cell proliferation. With careful validation, [18F]FLT-PET imaging can be used to monitor antiproliferative therapies in tracer-avid malignancies.
Clinical Cancer Research , résumé, 2011