Comprehensive Cancer Imaging Center, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Eur J Nucl Med Mol Imaging. 2011 Dec;38(12):2186-97. doi: 10.1007/s00259-011-1907-9. Epub 2011 Sep 3.
The purpose of the study was to estimate the receptor-ligand binding of an arginine-glycine-aspartic acid (RGD) peptide in somatic tumours. To this aim, we employed dynamic positron emission tomography (PET) data obtained from breast cancer patients with metastases, studied with the α(v)β(3/5) integrin receptor radioligand [(18)F]fluciclatide.
First, compartmental modelling and spectral analysis with arterial input function were performed at the region of interest (ROI) level in healthy lung and liver, and in lung and liver metastases; compartmental modelling was also carried out at the pixel level. The selection of the most appropriate indexes for tumour/healthy tissue differentiation and for estimation of specific binding was then assessed.
The two-tissue reversible model emerged as the best according to the Akaike Information Criterion. Spectral analysis confirmed the reversibility of tracer kinetics. Values of kinetic parameters, estimated as mean from parametric maps, correlated well with those computed from ROI analysis. The volume of distribution V(T) was on average higher in lung metastases than in the healthy lung, but lower in liver metastases than in the healthy liver. In agreement with the expected higher α(v)β(3/5) expression in pathology, k(3) and k(3)/k(4) were both remarkably higher in metastases, which makes them more suitable than V(T) for tumour/healthy tissue differentiation. The ratio k(3)/k(4), in particular, appeared a reasonable measure of specific binding.
Besides establishing the best quantitative approaches for the analysis of [(18)F]fluciclatide data, this study indicated that the k(3)/k(4) ratio is a reasonable measure of specific binding, suggesting that this index can be used to estimate α(v)β(3/5) receptor expression in oncology, although further studies are necessary to validate this hypothesis.
本研究旨在评估精氨酸-甘氨酸-天冬氨酸(RGD)肽在体瘤中的受体-配体结合。为此,我们使用了带有α(v)β(3/5)整合素受体放射性配体[(18)F]fluciclatide 的转移性乳腺癌患者的动态正电子发射断层扫描(PET)数据。
首先,在健康肺和肝、肺和肝转移灶的感兴趣区(ROI)水平进行了房室模型分析和动脉输入函数的谱分析;也在像素水平进行了房室模型分析。然后评估了用于肿瘤/健康组织区分和估计特异性结合的最佳指标。
根据赤池信息量准则,双室可逆模型是最佳选择。谱分析证实了示踪剂动力学的可逆性。从参数图中平均估计的动力学参数值与从 ROI 分析中计算出的参数值吻合良好。分布容积 V(T)在肺转移灶中平均高于健康肺,但在肝转移灶中低于健康肝。与病理学中预期的更高的 α(v)β(3/5)表达一致,k(3)和 k(3)/k(4)在转移灶中均显著升高,这使得它们比 V(T)更适合肿瘤/健康组织区分。特别是 k(3)/k(4)比值似乎是特异性结合的合理衡量标准。
本研究除了为 [(18)F]fluciclatide 数据的分析建立了最佳的定量方法外,还表明 k(3)/k(4)比值是特异性结合的合理衡量标准,提示该指数可用于估计肿瘤学中的α(v)β(3/5)受体表达,尽管还需要进一步的研究来验证这一假设。