Metabolic Imaging Allows Early Prediction of Response to Vandetanib

Journal of Nuclear Medicine

Isabel J. Hildebrandt¹  Michael E. Phelps¹  Johannes Czernin¹  Robert D. Damoiseaux¹  Andreas Bockisch¹  Verena Hartung¹  Wolfgang A. Weber¹  Rachel E. Laing¹  Matthias R. Benz¹  Martin A. Walter¹ 

关键词: animal imaging;    endocrinology;    oncology;    early treatment monitoring;    medullary thyroid cancer;    positron emission tomography;    tyrosine kinase inhibitor;    vandetanib;   

DOI  :  10.2967/jnumed.110.081745

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The RET (rearranged-during-transfection protein) protooncogene triggers multiple intracellular signaling cascades regulating cell cycle progression and cellular metabolism. We therefore hypothesized that metabolic imaging could allow noninvasive detection of response to the RET inhibitor vandetanib in vivo. Methods: The effects of vandetanib treatment on the full-genome expression and the metabolic profile were analyzed in the human medullary thyroid cancer cell line TT. In vitro, transcriptional changes of pathways regulating cell cycle progression and glucose, dopa, and thymidine metabolism were correlated to the results of cell cycle analysis and the uptake of 3H-deoxyglucose, 3H-3,4-dihydroxy-L-phenylalanine, and 3H-thymidine under vandetanib treatment. In vivo, the tumor metabolism under vandetanib was monitored by small-animal PET of tumor-bearing mice. Results: Vandetanib treatment resulted in the transcriptional downregulation of various effector pathways with consecutive downregulation of cyclin expression and a G0/G1 arrest. In vitro, vandetanib treatment resulted in the decreased expression of genes regulating glucose, 3,4-dihydroxy-L-phenylalanine, and thymidine metabolism, with a subsequent reduction in the functional activity of the corresponding pathways. In vivo, metabolic imaging with PET was able to assess changes in the tumoral glucose metabolism profile as early as 3 d after initiation of vandetanib treatment. Conclusion: We describe a metabolic imaging approach for the noninvasive detection of successful vandetanib treatment. Our results suggest that PET may be useful for identifying patients who respond to vandetanib early in the course of treatment.

【 授权许可】

Unknown