Is 3′-deoxy-3′-18F-fluorothymidine a better marker for tumour response than 18F-fluorodeoxyglucose?

Reske, Sven N.; Deisenhofer, Sandra

doi:10.1007/s00259-006-0134-2

Cited by 29 publications

(15 citation statements)

References 36 publications

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“…Thus, one may postulate that the 18 F-FLT uptake could increase in response to active DNA synthesis in any tissue, including growing microbes. The effect of 18 F-FLT transportation across cell membranes or a phosphorylation pathway other than thymidine kinase 1 should also be considered (10,11). Because of its nontumor uptake, 18 F-FLT might not be suitable to work alone or to replace 18 F-FDG in the diagnosis or differentiation of pulmonary lesions.…”

Section: Comparison Of 18 F-flt and 18 F-fdgmentioning

confidence: 99%

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-¹⁸F-Fluorothymidine and ¹⁸F-FDG

Tian¹,

Yang²,

Yu³

et al. 2008

J Nucl Med

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Some new radiotracers might add useful information and improve diagnostic confidence of 18 F-FDG imaging in tumors. A multicenter clinical trial was designed to investigate the diagnostic performance of dual-tracer ( 18 F-FDG and 39-deoxy-39-18 F-fluorothymidine [ 18 F-FLT]) PET/CT in pulmonary nodules. Methods: Fifty-five patients underwent dual-tracer imaging in 6 imaging centers using the same models of equipment and standardized protocols. The images were interpreted by a collective group of readers who were unaware of the clinical data. The diagnostic performance using either tracer alone or dual-tracers together, with or without CT, was compared. The histological diagnosis or clinical findings in a 12-mo follow-up period served as the standard of truth. Results: In 16 patients with malignant tumor, 16 with tuberculosis, and 23 with other benign lesions, the sensitivity and specificity of 18 F-FDG and 18 F-FLT were 87.5% and 58.97% and 68.75% and 76.92%, respectively. The combination of dual-tracer PET/CT improved the sensitivity and specificity up to 100% and 89.74%. The 3 subgroups of patients could be best separated when the 18 F-FLT/ 18 F-FDG standardized uptake value ratio of 0.4-0.90 was used as the threshold. Conclusion: By reflecting different biologic features, the dualtracer PET/CT using 18 F-FDG and 18 F-FLT favorably affected the diagnosis of lung nodules.

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Section: Comparison Of 18 F-flt and 18 F-fdgmentioning

confidence: 99%

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-¹⁸F-Fluorothymidine and ¹⁸F-FDG

Tian¹,

Yang²,

Yu³

et al. 2008

J Nucl Med

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“…After intravenous injection, FLT generally enters the cell by Na + -dependent active nucleoside transporters and to a lesser extent by passive diffusion [12,13]. The expression of transport proteins may be upregulated in tumour cells.…”

Section: Metabolism Of Fltmentioning

confidence: 99%

“…In the assessment of response to therapy by changes in proliferation markers, such as Ki-67 and TK 1 levels, should be correlated with changes in FLT uptake [11]. Treatment-induced changes in the expression of nucleoside transport proteins and key enzymes of thymidine synthesis need to be evaluated before the flux of FLT through the thymidine salvage pathway can be used as a reliable treatment response parameter [12]. In addition, further work is required to determine the best method to analyse FLT data.…”

Section: Future Directionsmentioning

confidence: 99%

Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: a comprehensive evaluation

Barwick

Bencherif

Mountz

et al. 2009

Nuclear Medicine Communications

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Positron emission tomography (PET) using F-18 fluoro-3'-deoxy-3-L-fluorothymidine (FLT) offers noninvasive assessment of cell proliferation in vivo. The most important application refers to the evaluation of tumour proliferative activity, representing a key feature of malignancy. Most data to date suggest that FLT is not a suitable biomarker for staging of cancers. This is because of the rather low fraction of tumour cells that undergo replication at a given time with subsequently relatively low tumour FLT uptake. In addition, generally, the high FLT uptake in liver and bone marrow limits the diagnostic use. We describe the current status on preclinical and clinical applications of FLT-PET including our own experience in brain tumours. The future of FLT-PET probably lies in the evaluation of tumour response to therapy and more importantly, in the prediction of early response in the course of treatment. The level of FLT accumulation in tumours depends on thymidine kinase 1 activity and on the therapy-induced activation of the salvage pathway and expression of nucleoside transporters. Therefore, cytostatic agents that cause arrest of the cell cycle in the S-phase may initially increase FLT uptake rather than reducing the tumour cell accumulation. In addition, agents that block the endogenous thymidine pathway may lead to overactivity of the salvage pathway and increase tumour FLT uptake. In contrast, many therapeutic agents inhibit both pathways and subsequently reduce tumour FLT uptake. Further studies comparing FLT with F-18 fluorodeoxyglucose-PET will be important to determine the complementary advantage of FLT-PET in early cancer therapy response assessment. Further research should be facilitated by simplified synthesis of FLT with improved yields and an increasing commercial availability.

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“…Importantly, 3′-[ 18 F]fluoro-3′-deoxythymidine ([ 18 F]FLT) has been proposed as the long sought-after agent for noninvasive PET imaging of cellular proliferation and monitoring tumor response to therapy [4, 5]. Recently, [ 18 F]FLT has been developed as a radiotracer targeted to the activity of thymidine kinase 1 (TK-1) for imaging tumor cellular proliferation, a potential indicator of response to therapy [6–9]. [ 18 F]FLT is one of the most promising 18 F PET tracers because of its in vivo stability, metabolic trapping in proliferating cells, and a favorable physical half-life (110 min) for PET imaging [1, 4, 10].…”

Section: Introductionmentioning

confidence: 99%

A Novel In Vitro Assay to Assess Phosphorylation of 3′-[18F]fluoro-3′-Deoxythymidine

et al. 2010

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Purpose 3′-[18F]fluoro-3’-deoxythymidine ([18F]FLT) is phosphorylated by thymidine kinase 1 (TK-1), a cell cycle regulated enzyme. Appropriate use of [18F]FLT tracer requires validation of the TK-1 activity. Here, we report development of a novel phosphoryl-transfer assay to assess phosphorylation of [18F]FLT both in tumor cell lysates and tumor cells. Procedures The intrinsic F-18 radioactivity was used to quantify both substrate and phosphorylated products using a rapid thin layer chromatography method. Phosphorylation kinetics of [18F]FLT in SW480 and DiFi tumor cell lysates and cellular uptake were measured. Results The apparent Michaelis–Menten kinetic parameters for [18F]FLT are Km = 4.8 ± 0.3 μM and Vmax=7.4 pmol min−1per 1×106 cells with ~2-fold higher TK-1 activity in DiFi versus SW480 lysates. Conclusions The apparent Km of [18F]FLT was comparable to the value reported with purified recombinant TK-1. The uptake of [18F]FLT by SW480 cells is inhibited by nitrobenzylthioinosine or dipyridamole indicating that uptake is mediated predominantly by the equilibrative nucleoside transporters in these tumor cells.

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Is 3′-deoxy-3′-18F-fluorothymidine a better marker for tumour response than 18F-fluorodeoxyglucose?

Cited by 29 publications

References 36 publications

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-¹⁸F-Fluorothymidine and ¹⁸F-FDG

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-¹⁸F-Fluorothymidine and ¹⁸F-FDG

Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: a comprehensive evaluation

A Novel In Vitro Assay to Assess Phosphorylation of 3′-[18F]fluoro-3′-Deoxythymidine

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Is 3′-deoxy-3′-18F-fluorothymidine a better marker for tumour response than 18F-fluorodeoxyglucose?

Cited by 29 publications

References 36 publications

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-18F-Fluorothymidine and 18F-FDG

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-18F-Fluorothymidine and 18F-FDG

Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: a comprehensive evaluation

A Novel In Vitro Assay to Assess Phosphorylation of 3′-[18F]fluoro-3′-Deoxythymidine

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A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-¹⁸F-Fluorothymidine and ¹⁸F-FDG

A Multicenter Clinical Trial on the Diagnostic Value of Dual-Tracer PET/CT in Pulmonary Lesions Using 3′-Deoxy-3′-¹⁸F-Fluorothymidine and ¹⁸F-FDG