Abstract | 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 (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.
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Authors | J 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 |
Journal | Journal 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 |
PMID | 21764789
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Ki-67 Antigen
- Fluorodeoxyglucose F18
- Thymidine Kinase
- thymidine kinase 1
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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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