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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.

AbstractUNLABELLED:
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 (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 (18)F-FLT PET revealed correlations between the flux constant (K(FLT)) and both overall (ρ = 0.53, P = 0.014) and maximal (ρ = 0.50, P = 0.020) TK1 protein expression. K(FLT) 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 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.
AuthorsJ Scott Brockenbrough, Timothee Souquet, Janice K Morihara, Joshua E Stern, Stephen E Hawes, Janet S Rasey, Antoine Leblond, Linda W Wiens, Qinghua Feng, John Grierson, Hubert Vesselle
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 52 Issue 8 Pg. 1181-8 (Aug 2011) ISSN: 1535-5667 [Electronic] United States
PMID21764789 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Ki-67 Antigen
  • Fluorodeoxyglucose F18
  • Thymidine Kinase
  • thymidine kinase 1
Topics
  • Cell Cycle
  • Cell Proliferation
  • Cohort Studies
  • Female
  • Fluorodeoxyglucose F18 (pharmacology)
  • Humans
  • Immunohistochemistry (methods)
  • Ki-67 Antigen (biosynthesis)
  • Kinetics
  • Lung Neoplasms (diagnostic imaging, pathology)
  • Male
  • Positron-Emission Tomography (methods)
  • Prognosis
  • Thymidine Kinase (biosynthesis)
  • Time Factors

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