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Machulla, H.-J.; Blocher, A.; Kuntzsch, Matthias; Piert, Morand; Wei, Rongqing; Grierson, John R.

doi:10.1023/a:1010684101509

Cited by 173 publications

(21 citation statements)

References 1 publication

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“…FLT was either synthesized in-house as described in [24] or externally supplied (PETNET Solutions Inc., Nottingham, UK or Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK).…”

Section: Methodsmentioning

confidence: 99%

Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

Trigonis

Koh

Taylor

et al. 2014

Eur J Nucl Med Mol Imaging

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PurposeChanges in tumour 3′-deoxy-3′-[18F]fluorothymidine (FLT) uptake during concurrent chemo-radiotherapy in patients with non-small cell lung cancer (NSCLC) have been reported, at variable time points, in two pilot positron emission tomography (PET) studies. The aim of this study was to assess whether FLT changes occur early in response to radiotherapy (RT) without concurrent chemotherapy and whether such changes exceed test-retest variability.MethodsSixteen patients with NSCLC, scheduled to have radical RT, underwent FLT PET once/twice at baseline to assess reproducibility and/or after 5–11 RT fractions to evaluate response. Primary and nodal malignant lesions were manually delineated on CT and volume, mean and maximum standardized uptake values (SUVmean and SUVmax) estimated. Analysis included descriptive statistics and parameter fitting to a mixed-effects model accounting for patients having different numbers of evaluable lesions.ResultsIn all, 35 FLT PET scans from 7 patients with a total of 18 lesions and 12 patients with a total of 30 lesions were evaluated for reproducibility and response, respectively. SUVmean reproducibility in primary tumours (SD 8.9 %) was better than SUVmax reproducibility (SD 12.6 %). In nodes, SUVmean and SUVmax reproducibilities (SD 18.0 and 17.2 %) were comparable but worse than for primary tumours. After 5–11 RT fractions, primary tumour SUVmean decreased significantly by 25 % (p = 0.0001) in the absence of significant volumetric change, whereas metastatic nodes decreased in volume by 31 % (p = 0.020) with a larger SUVmean decrease of 40 % (p < 0.0001). Similar changes were found for SUVmax.ConclusionAcross this group of NSCLC patients, RT induced an early, significant decrease in lesion FLT uptake exceeding test-retest variability. This effect is variable between patients, appears distinct between primary and metastatic nodal lesions, and in primary tumours is lower than previously reported for concurrent chemo-RT at a similar time point. These results confirm the potential for FLT PET to report early on radiation response and to enhance the clinical development of novel drug-radiation combinations by providing an interpretable, early pharmacodynamic end point.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-013-2632-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Early reduction in tumour [18F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone

Trigonis

Koh

Taylor

et al. 2014

Eur J Nucl Med Mol Imaging

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“…The radiosynthesis of 18 F-FLT was produced according to a method already described [13,14,15]. Briefly, fluorine-18 fluoride is prepared by the 18 O (p, n) 18 F reaction using >95% 18 O enriched water as the target material with a titanium window and target holder.…”

Section: Methodsmentioning

confidence: 99%

“…Kryptofix ® (Sigma-Aldrich, Gillingham, UK)/potassium carbonate solution and the fluoride is dried by azeotropic distillation with acetonitrile. The 18 F fluoride is then reacted with the 5′-benzoate of 2,3′-anhydrothymine in DMSO at 160 °C [15]; then, after cooling down to 50 °C, 1% NaOH (0.35 mL) heated to 50 °C, 0.2 M NaH 2 PO 4 (0.75 mL), and 1.5 mL of 8% EtOH/92% 0.01 M NaH 2 PO 4 are added before passing through an alumina cartridge and loaded on a preparative HPLC column. The FLT is purified by high-performance liquid chromatography on an 18 C reversed phase column using 8% ethanol/92% 0.01 M NaH 2 PO 4 as the mobile phase.…”

Section: Methodsmentioning

confidence: 99%

An Assessment of Early Response to Targeted Therapy via Molecular Imaging: A Pilot Study of 3′-deoxy-3′[(18)F]-Fluorothymidine Positron Emission Tomography 18F-FLT PET/CT in Prostate Adenocarcinoma

et al. 2017

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Fluorothymidine is a thymidine analog labeled with fluorine-18 fluorothymidine for positron emission tomography (18F-FLT-PET) imaging. Thymidine is a nucleic acid that is used to build DNA. Fluorine-18 fluorothymidine (18F-FLT) utilizes the same metabolic pathway as does thymidine but has a very low incidence of being incorporated into the DNA (<1%). 18F-FLT-PET could have a role in the evaluation of response to targeted therapy. We present here a pilot study where we investigated cellular metabolism and proliferation in patients with prostate cancer before and after targeted therapy. Seven patients with Stage IV prostate adenocarcinoma, candidates for targeted therapy inhibiting the hepatocyte growth factor/tyrosine-protein kinase Met (HGF/C-MET) pathway, were included in this study. The HGF/C-MET pathway is implicated in prostate cancer progression, and an evaluation of the inhibition of this pathway could be valuable. 18F-FLT was performed at baseline and within four weeks post-therapy. Tumor response was assessed semi-quantitatively and using visual response criteria. The range of SUVmax for 18F-FLT at baseline in the prostate varied from 2.5 to 4.2. This study demonstrated that 18F-FLT with positron emission tomography/computerized tomography (18F-FLT PET/CT) had only limited applications in the early response evaluation of prostate cancer. 18F-FLT PET/CT may have some utility in the assessment of response in lymph node disease. However, 18F-FLT PET/CT was not found to be useful in the evaluation of the prostate bed, metastatic skeletal disease, and liver disease.

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“…Beyond the room temperature Silicon Fluoride Acceptor (SiFA) based radiochemistry employed in this study, COC is compatible with process temperatures of up to 150°C such as for the synthesis of the PET tracer, [18F]fluorothymidine ([18F]FLT). 53 COC is further marked by its low raw material cost of around one cent (US) per gram.…”

Section: Microfluidic Chip Manufacturingmentioning

confidence: 99%