Tumor 3′-Deoxy-3′-18F-Fluorothymidine (18F-FLT) Uptake by PET Correlates with Thymidine Kinase 1 Expression: Static and Kinetic Analysis of 18F-FLT PET Studies in Lung Tumors

Journal of Nuclear Medicine

Qinghua Feng¹  Timothee Souquet¹  Hubert Vesselle¹  J. Scott Brockenbrough¹  John Grierson¹  Joshua E. Stern¹  Stephen E. Hawes¹  Linda W. Wiens¹  Janice K. Morihara¹  Antoine Leblond¹  Janet S. Rasey¹ 

关键词: positron emission tomography (PET);    ¹⁸F-FLT;    3′-deoxy-3′-fluorothymidine;    thymidine kinase 1;    tumor proliferation;    lung tumors;   

DOI  :  10.2967/jnumed.111.089482

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

We report the first, to our knowledge, findings describing the relationships between both static and dynamic analysis parameters of 3′-deoxy-3′-18F-fluorothymidine (18F-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 18F-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 18F-FLT uptake (partial-volume–corrected maximum-pixel standardized uptake value from 60- to 90-min summed dynamic data) was significantly correlated with the overall (ρ = 0.57, P = 0.006) and maximal (ρ = 0.69, P < 0.001) immunohistochemical expressions of Ki-67 and TK1 (overall expression: ρ = 0.65, P = 0.001; maximal expression: ρ = 0.68, P < 0.001) but not with TK1 enzymatic activity (ρ = 0.34, P = 0.146). TK1 activity was significantly correlated with TK1 protein expression only when immunohistochemistry was scored for maximal expression (ρ = 0.52, P = 0.029). Dynamic analysis of 18F-FLT PET revealed correlations between the flux constant (KFLT) and both overall (ρ = 0.53, P = 0.014) and maximal (ρ = 0.50, P = 0.020) TK1 protein expression. KFLT was also associated with both overall (ρ = 0.59, P = 0.005) and maximal (ρ = 0.63, P = 0.002) Ki-67 expression. We observed no significant correlations between TK1 enzyme activity and KFLT. 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 18F-FLT uptake and retention within cells may be complicated by a variety of still undetermined factors in addition to TK1 enzymatic activity.

【 授权许可】

Unknown