Quantitative PET of Human Urokinase-Type Plasminogen Activator Receptor with 64Cu-DOTA-AE105: Implications for Visualizing Cancer Invasion

Journal of Nuclear Medicine

Søren Østergaard¹  Andreas Kjaer¹  Charlotte Lehmann¹  Mette Munk Jensen¹  Jacob Madsen¹  Morten Persson¹  Michael Ploug¹  Jesper Tranekjær Jørgensen¹  Karina Juhl¹ 

关键词: molecular imaging;    uPAR;    CD87;    PET;    cancer invasion;    ⁶⁴Cu;   

DOI  :  10.2967/jnumed.110.083386

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expression levels of uPAR across different human cancer xenograft models in mice and to illustrate the clinical potential of uPAR PET in future settings for individualized therapy. Methods: To accomplish our objective, a linear, high-affinity uPAR peptide antagonist, AE105, was conjugated with DOTA and labeled with 64Cu (64Cu-DOTA-AE105). Small-animal PET was performed in 3 human cancer xenograft mice models, expressing different levels of human uPAR, and the tumor uptake was correlated with the uPAR expression level determined by uPAR enzyme-linked immunosorbent assay. The tumor uptake pattern of this tracer was furthermore compared with 18F-FDG uptake, and finally the correlation between sensitivity toward 5-fluorouracil therapy and uPAR expression level was investigated. Results: The uPAR-targeting PET tracer was produced in high purity and with high specific radioactivity. A significant correlation between tumor uptake of 64Cu-DOTA-AE105 and uPAR expression was found (R2 = 0.73; P < 0.0001) across 3 cancer xenografts, thus providing a strong argument for specificity. A significantly different uptake pattern of 64Cu-DOTA-AE105, compared with that of 18F-FDG, was observed, thus emphasizing the additional information that can be obtained on tumor biology using 64Cu-DOTA-AE105 PET. Furthermore, a significant correlation between baseline uPAR expression and sensitivity toward 5-fluorouracil was revealed, thus illustrating the possible potentials of uPAR PET in a clinical setting. Conclusion: Our results clearly demonstrate that the peptide-based PET tracer 64Cu-DOTA-AE105 enables the noninvasive quantification of uPAR expression in tumors in vivo, thus emphasizing its potential use in a clinical setting to detect invasive cancer foci and for individualized cancer therapy.

【 授权许可】

Unknown