RT Journal Article
SR Electronic
T1 Tumor 3′-Deoxy-3′-<sup>18</sup>F-Fluorothymidine (<sup>18</sup>F-FLT) Uptake by PET Correlates with Thymidine Kinase 1 Expression: Static and Kinetic Analysis of <sup>18</sup>F-FLT PET Studies in Lung Tumors
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1181
OP 1188
DO 10.2967/jnumed.111.089482
VO 52
IS 8
A1 Brockenbrough, J. Scott
A1 Souquet, Timothee
A1 Morihara, Janice K.
A1 Stern, Joshua E.
A1 Hawes, Stephen E.
A1 Rasey, Janet S.
A1 Leblond, Antoine
A1 Wiens, Linda W.
A1 Feng, Qinghua
A1 Grierson, John
A1 Vesselle, Hubert
YR 2011
UL http://jnm.snmjournals.org/content/52/8/1181.abstract
AB 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 &lt; 0.001) immunohistochemical expressions of Ki-67 and TK1 (overall expression: ρ = 0.65, P = 0.001; maximal expression: ρ = 0.68, P &lt; 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.