Tumor 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) uptake by PET correlates with thymidine kinase 1 expression: static and kinetic analysis of (18)F-FLT PET studies in lung tumors.
Tumor 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) uptake by PET correlates with thymidine kinase 1 expression: static and kinetic analysis of (18)F-FLT PET studies in lung tumors.
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DOI：
10.2967/jnumed.111.089482
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发表时间：
2011-08-01
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影响因子：
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通讯作者：
Vesselle, Hubert
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文献类型：
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作者：
Brockenbrough, J Scott;Souquet, Timothee;Vesselle, Hubert
未贴标：据我们所知，我们报告了第一个描述3 '-脱氧-3'-（18）F-氟胸苷（（18）F-FLT）PET的静态和动态分析参数与增殖标记物Ki-67的表达以及手术切除的肺病变中胸苷激酶-1（TK 1）的蛋白表达和酶活性之间关系的结果。在手术切除前对25例前瞻性累积的临床疑似肺癌患者（1例病变在手术后发现为良性）的18个F-FLT PET图像进行静态和动态分析（4个速率常数和2个房室）。免疫组化半定量分析Ki-67和TK 1的最大和总平均表达。TK 1酶活性通过从相同肿瘤的快速冷冻样品制备的提取物的体外测定来确定。静态（18）F-FLT摄取（部分容积校正的最大像素标准化摄取值，从60分钟到90分钟的动态数据总和）与总体（rho = 0.57，P = 0.006）和最大值Ki-67和TK 1的免疫组化表达（rho = 0.69，P < 0.001）（总表达：rho = 0.65，P = 0.001;最大表达：rho = 0.68，P < 0.001），但不具有TK 1酶活性（rho = 0.34，P = 0.146）。TK 1活性与TK 1蛋白表达仅在免疫组化评分为最大表达时显著相关（rho = 0.52，P = 0.029）。（18）F-FLT PET的动态分析显示通量常数（K（FLT））与TK 1蛋白的总体（rho = 0.53，P = 0.014）和最大（rho = 0.50，P = 0.020）表达之间存在相关性。K（FLT）也与总体（rho = 0.59，P = 0.005）和最大（rho = 0.63，P = 0.002）Ki-67表达相关。我们没有观察到TK 1酶活性和K（FLT）之间的显着相关性。此外，TK 1的表达，TK 1的活性，或Ki-67的表达和任何房室速率constants.CONCLUSION：可观察到的相关性的成像参数与TK 1的活性的情况下，没有发现显着的关系表明，（18）F-FLT的摄取和保留在细胞内可能是复杂的各种尚未确定的因素，除了TK 1酶的活性。
UNLABELLED: We report the first, to our knowledge, findings describing the relationships between both static and dynamic analysis parameters of 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) PET and the expression of the proliferation marker Ki-67, and the protein expression and enzymatic activity of thymidine kinase-1 (TK1) in surgically resected lung lesions.METHODS: Static and dynamic analyses (4 rate constants and 2 compartments) of (18)F-FLT PET images were performed in a cohort of 25 prospectively accrued, clinically suspected lung cancer patients before surgical resection (1 lesion was found to be benign after surgery). The maximal and overall averaged expression of Ki-67 and TK1 were determined by semiquantitative analysis of immunohistochemical staining. TK1 enzymatic activity was determined by in vitro assay of extracts prepared from flash-frozen samples of the same tumors.RESULTS: Static (18)F-FLT uptake (partial-volume-corrected maximum-pixel standardized uptake value from 60- to 90-min summed dynamic data) was significantly correlated with the overall (rho = 0.57, P = 0.006) and maximal (rho = 0.69, P < 0.001) immunohistochemical expressions of Ki-67 and TK1 (overall expression: rho = 0.65, P = 0.001; maximal expression: rho = 0.68, P < 0.001) but not with TK1 enzymatic activity (rho = 0.34, P = 0.146). TK1 activity was significantly correlated with TK1 protein expression only when immunohistochemistry was scored for maximal expression (rho = 0.52, P = 0.029). Dynamic analysis of (18)F-FLT PET revealed correlations between the flux constant (K(FLT)) and both overall (rho = 0.53, P = 0.014) and maximal (rho = 0.50, P = 0.020) TK1 protein expression. K(FLT) was also associated with both overall (rho = 0.59, P = 0.005) and maximal (rho = 0.63, P = 0.002) Ki-67 expression. We observed no significant correlations between TK1 enzyme activity and K(FLT). In addition, no significant relationships were found between TK1 expression, TK1 activity, or Ki-67 expression and any of the compartmental rate constants.CONCLUSION: The absence of observable correlations of the imaging parameters with TK1 activity suggests that (18)F-FLT uptake and retention within cells may be complicated by a variety of still undetermined factors in addition to TK1 enzymatic activity.