Search

Purpose: This review aimed to summarize the available literature on the clinical application of [18F] FLT PET imaging in primary brain tumours. Methods: A comprehensive search strategy based on Pubmed/Medline, Scopus, Web of Science, Cochrane Library, Google Scholar, and the Embase databases was carried on using the following search string: ('3` Fluorothymidine'/exp OR 'FLT' OR '[18F]-FLT' OR '[18F] Fluorothymidine') AND ('pet'/exp OR 'pet' OR 'positron emission tomography') AND ('glioma'/exp OR 'glioma' OR 'brain tumour'/exp OR 'brain tumour’). The search was updated till March 2021 and only articles in English and studies investigating the clinical applications of [18F] FLT PET and PET/CT in primary brain tumours were considered eligible for inclusion. Results: The literature search ultimately yielded 52 studies included in the systematic review, with main results as follows: a) the uptake of [18F] FLT may guide stereotactic biopsy but does not discriminate between grade II and III glioma. b) [18F] FLT uptake and texture parameters correlate with overall survival (OS) in newly diagnosed gliomas. c) In patients with recurrent glioma, proliferative volume (PV) and tumour-to-normal brain (T/N) uptake ratio are independent predictors of survival. d) Patients demonstrating response to therapy at [18F] FLT PET scan show longer OS compared to non-responders. e) [18F] FLT PET demonstrated good performance in discriminating tumour recurrence from radionecrosis. However, controversial results exist in comparative literature examining the performance of [18F] FLT vs. other radiotracers in the assessment of recurrence. Conclusion: [18F] FLT PET imaging has demonstrated potential benefits for grading, diagnostic and prognostic purposes, despite the small sample size studies due to the relatively low availability of the radiotracer.

Lung cancer has the highest mortality rate of any tumour type. The main driver of lung tumour growth and development is uncontrolled cellular proliferation. Poor patient outcomes are partly the result of the limited range of effective anti-cancer therapies available and partly due to the limited accuracy of biomarkers to report on cell proliferation rates in patients. Accordingly, accurate methods of diagnosing, staging and assessing response to therapy are crucial to improve patient outcomes. One effective way of assessing cell proliferation is to employ non-invasive evaluation using 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography [18F]FLT-PET. [18F]FLT, unlike the most commonly used PET tracer [18F]fluorodeoxyglucose ([18F]FDG), can specifically report on cell proliferation and does not accumulate in inflammatory cells. Therefore, this radiotracer could exhibit higher specificity in diagnosis and staging, along with more accurate monitoring of therapy response at early stages in the treatment cycle. This review summarises and evaluates published studies on the clinical use of [18F]FLT to diagnose, stage and assess response to therapy in lung cancer.

Accurate disease monitoring is essential following transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) due to potential for profound adverse event and large variation in survival outcome. Post-treatment changes on conventional imaging can confound determination of residual/recurrent disease, magnifying the clinical challenge. Based on increased expression of thymidylate synthase (TYMS), thymidine kinase-1 (TK-1) and SLC29A1 (Equilibrative nucleoside transporter 1, ENT1) in HCC compared with liver tissue, we conducted a proof of concept study evaluating the efficacy of 18F-fluorothymidine (18F-FLT)-PET to assess response to TACE. As previous PET studies in HCC have been hampered by high background liver signal, we investigated if a temporal-intensity voxel-clustering ("Kinetic Spatial Filtering") (KSF) improved lesion detection. Methods: A tissue microarray (TMA) was built from 36 HCC samples and matched surrounding cirrhotic tissue and was stained for thymidine kinase-1 (TK-1). A prospective study was conducted; eighteen patients with a diagnosis of HCC by American Association for the Study of Liver Diseases criteria (AALSD) who were eligible to treatment with TACE were enrolled. Patients underwent baseline conventional imaging and dynamic 18F-FLT-PET/KSF followed by TACE. Repeat imaging was performed 6-8 weeks post TACE. PET parameters were compared with modified-Response Evaluation in Solid Tumours (mRECIST) enhancement-based criteria. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1 and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC (p

Supplemental Digital Content is available in the text, Objective: To investigate whether [18F]fluorothymidine (FLT) and/or [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) can differentiate growth in neurofibromatosis 2 (NF2) related vestibular schwannomas (VS) and to evaluate the importance of PET scanner spatial resolution on measured tumor uptake. Methods: Six NF2 patients with 11 VS (4 rapidly growing, 7 indolent), were scanned with FLT and FDG using a high-resolution research tomograph (HRRT, Siemens) and a Siemens Biograph TrueV PET-CT, with and without resolution modeling image reconstruction. Mean, maximum, and peak standardised uptake values (SUV) for each tumor were derived and the intertumor correlation between FDG and FLT uptake was compared. The ability of FDG and FLT SUV values to discriminate between rapidly growing and slow growing (indolent) tumors was assessed using receiver operator characteristic (ROC) analysis. Results: Tumor uptake was seen with both tracers, using both scanners, with and without resolution modeling. FDG and FLT uptake was correlated (R2 = 0.67–0.86, p

18F-FDG accumulates not only in malignant lesions but also in infectious and inflammatory ones. 3'-deoxy-3'-18F-fluorothymidine (FLT) has been investigated as a promising PET tracer for evaluating tumor proliferating activity. We report a case of liver abscess during therapy of pancreatic cancer that underwent FDG PET/CT and FLT PET/CT studies. Although FDG PET/CT demonstrated several regions of increased uptake in the liver, FLT PET/CT showed no increased uptake in the liver.

Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

A 64-year-old man with no significant medical history demonstrated a right lower lobe opacity on routine chest radiography. Transaxial CT showed a round, well-circumscribed, pleural mass with comet-tail sign in the right lower lobe and pleural thickening with pleural effusion. F-FDG PET/CT showed hypermetabolic activity in the mass (SUVmax 9.61). F-fluorothymidine PET/CT also showed mild increased uptake in the mass (SUVmax 3.26). Lung biopsy and follow-up CT scan revealed round atelectasis.

// Hinrich Wieder 1, 2 , Ambros J. Beer 1, 9 , Jens Siveke 3 , Tibor Schuster 4 , Andreas K. Buck 5 , Ken Herrmann 6 and Jens C. Stollfuss 7, 8 1 Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitat, Munchen, Munich, Germany 2 Centre for Radiology and Nuclear Medicine, Grevenbroich, Germany 3 Division of Solid Tumor Translational Oncology, German Cancer Consortium, Partner Site Essen, Universitatsklinikum Essen, Essen, Germany 4 Department of Family Medicine, McGill University, Montreal, Quebec, Canada 5 Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany 6 Department of Nuclear Medicine, Universitatsklinikum Essen, Essen, Germany 7 Institute for Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany 8 Department of Radiology and Nuclear Medicine, Klinikum Memmingen, Memmingen, Germany 9 Department of Nuclear Medicine, Ulm University, Ulm, Germany Correspondence to: Hinrich Wieder, email: h@wieder.de Keywords: FLT; PET; pancreas; predictive value; outcome prognosis Received: August 16, 2017 Accepted: December 01, 2017 Published: January 12, 2018 ABSTRACT Purpose: The aim of this study was to correlate preoperative 3'-deoxy-3'-[ 18 F] fluorothymidine (FLT) uptake with the clinical outcome and survival in these patients after surgery. Materials and Methods: We performed a prospective analysis in 27 patients with adenocarcinoma of the pancreas (15 males, 12 females, mean age: 62 ± 13 years, range: 34 – 86 years). FLT PET (45 min p.i., 300 MBq FLT; ECAT HR+) images were acquired according to standard protocols. FLT uptake was quantified using standardised uptake values (SUV). Mean follow-up was 35 months (range 24-49). FLT uptake was correlated with survival using Martingale residual analysis. Results: Twenty-two patients died during follow-up. Mean overall survival was 18.8 months (SD: 12.7 months, 95% CI: 7.7, 26.5). FLT PET showed a mean SUV of 2.5 (range: 1.1 - 6.5). Martingale residual analysis revealed significant correlation between survival and FLT uptake ( p = 0.045). The corresponding estimated hazard ratio per one-point increment of SUVmean was 1.298 (95% CI: 1.001, 1.685; p < 0.05). Conclusions: FLT PET allows risk stratification for death in patients with resectable pancreatic cancer prior to surgery.

An asymmetric synthesis of a 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) precursor has been developed wherein the deoxysugar moiety was synthesized using a novel Ga-mediated allylation of (R)-2,3-cyclohexylideneglyceraldehyde as the key step. The synthesis deviates significantly from the previous syntheses of the 18F-FLT precursors wherein the expensive starting material, thymidine was used.

F-Fluorothymidine-positron emission tomography with CT fusion ([F]FLT-PET/CT) offers a unique and non-invasive method for three-dimensional localization and quantification of functional bone marrow. [F]FLT-PET/CT has potential application in radiotherapy planning when risk of marrow toxicity is a significant clinical concern. In this patient with chemo-refractory, transformed lymphoma and treatment-induced cytopenias, [F]FLT-PET/CT was a novel and useful adjunct to (1) image the distribution of functional bone marrow reserve, (2) guide "marrow-sparing" radiotherapy planning, and (3) quantify the effects of radiotherapy-induced bone marrow suppression both in-field and out-of-field.

Human papillomavirus (HPV) has been usually associated with gynaecological cancers; however, recent studies have shown that this virus plays an important role in head and neck cancer. The aim of this study was to correlate PET/CT parameters in HPV-positive (HPV) and HPV-negative (HPV) patients using three tracers showing glucose metabolism, proliferation and hypoxia.Thirty-six patients (10 females and 26 males) with newly diagnosed head and neck cancer were enroled to this retrospective study. All patients underwent a series of three PET/CT scans with fluorine-18-fluorodeoxyglucose (F-FDG), fluorine-18-fluorothymidine (F-FLT) and fluorine-18-fluoromisonidazole (F-FMISO). Scans were performed on separate days, within a time-frame of 2 weeks. We compared several PET/CT parameters grading tumour biology including maximum standardized uptake value (SUV), total lesion glycolysis, totalSUV and heterogeneity between HPV and HPV patients. For statistical analysis, t-test and Mann-Whitney test were used and the materiality level of P values less than 0.05 were considered significant.Patient with HPV showed higher SUV values than patients with HPV in F-FLT images (6.34±2.5 vs. 5.99±3.6) and F-FMISO images (1.66±0.33 vs. 1.62±1.28) and lower values in F-FDG images (9.99±3.85 vs. 10.28±2.44). However, analyzing total lesion glycolysis values in all tracers, HPV patients showed higher values than HPV patients [F-FDG (92.21±102.9 vs. 70.83±74.27), F-FMISO (30.75±30.1 vs. 25.13±31.34) and F-FLT (138.71±132.9 vs. 109.61±92.7)].In our preliminary and limited study, we did not observe statistically significant differences in tumour metabolism, proliferation and hypoxia between the HPV and HPVpatients. However HPV patients tend to have higher proliferation status and more pronounced hypoxia with lower glucose metabolism.

AIM To establish patient-individual tumor models of rectal cancer for analyses of novel biomarkers, individual response prediction and individual therapy regimens. METHODS Establishment of cell lines was conducted by direct in vitro culturing and in vivo xenografting with subsequent in vitro culturing. Cell lines were in-depth characterized concerning morphological features, invasive and migratory behavior, phenotype, molecular profile including mutational analysis, protein expression, and confirmation of origin by DNA fingerprint. Assessment of chemosensitivity towards an extensive range of current chemotherapeutic drugs and of radiosensitivity was performed including analysis of a combined radio- and chemotherapeutic treatment. In addition, glucose metabolism was assessed with 18F-fluorodeoxyglucose (FDG) and proliferation with 18F-fluorothymidine. RESULTS We describe the establishment of ultra-low passage rectal cancer cell lines of three patients suffering from rectal cancer. Two cell lines (HROC126, HROC284Met) were established directly from tumor specimens while HROC239 T0 M1 was established subsequent to xenografting of the tumor. Molecular analysis classified all three cell lines as CIMP-0/ non-MSI-H (sporadic standard) type. Mutational analysis revealed following mutational profiles: HROC126: APCwt, TP53wt, KRASwt, BRAFwt, PTENwt; HROC239 T0 M1: APCmut, P53wt, KRASmut, BRAFwt, PTENmut and HROC284Met: APCwt, P53mut, KRASmut, BRAFwt, PTENmut. All cell lines could be characterized as epithelial (EpCAM+) tumor cells with equivalent morphologic features and comparable growth kinetics. The cell lines displayed a heterogeneous response toward chemotherapy, radiotherapy and their combined application. HROC126 showed a highly radio-resistant phenotype and HROC284Met was more susceptible to a combined radiochemotherapy than HROC126 and HROC239 T0 M1. Analysis of 18F-FDG uptake displayed a markedly reduced FDG uptake of all three cell lines after combined radiochemotherapy. CONCLUSION These newly established and in-depth characterized ultra-low passage rectal cancer cell lines provide a useful instrument for analysis of biological characteristics of rectal cancer.

TAS-102 is an orally administered anticancer agent composed of α,α,α-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). This study assessed 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake after TAS-102 administration.The human colorectal carcinoma cell lines HCT116, HT29, HCT8 and SW620 were exposed to FTD for 2 h, further incubated for 0, 2 and 24 h, and assayed for [(3)H]FLT uptake, nucleoside transport, thymidine kinase 1 (TK1) expression and TK1 activity. Static and 2-h dynamic [(18)F]FLT positron emission tomography (PET) was performed in mice bearing HT29 or SW620 tumours orally administered with vehicle or TAS-102.FTD decreased the viability of all cell lines, whereas increased [(3)H]FLT uptake (P 0.05). Increased nucleoside transport and/or TK1 expression were observed 24 h after FTD, but not in 0-2 h. Static [(18)F]FLT PET in mice bearing HT29 tumours showed accumulation of [(18)F]FLT in tumours 1 h (day 1) after TAS-102. Two-hour dynamic PET in mice bearing SW620 tumours showed increased influx constant and volume of distribution of phosphorylated [(18)F]FLT on days 1 and 8 (P 0.05) after TAS-102 with decreased dephosphorylation on day 1 (P 0.001). Ex vivo studies showed that SW620 tumours after TAS-102 had higher TK1 expression than those with vehicle on days 8 and 15.TAS-102 administration induces an increase in [(18)F]FLT uptake. Mechanisms may involve decreased dephosphorylation of [(18)F]FLT phosphate early after TAS-102 administration. Increased TK1 expression and/or nucleoside transporter may be related to increased [(18)F]FLT uptake at a later time. [(18)F]FLT PET has a potential to assess the pharmacodynamics of TAS-102 in cancer patients.

Microscale radiosynthesis on a miniaturized device has been reported as a promising tool for positron emission tomography. Here, we studied miscroscale-level radiosynthetic conditions by examining several microscale reactions that affect the radiochemical yield of 3′-deoxy-3′-[ 18 F]fluorothymidine ([ 18 F]FLT). [ 18 F]FLT was prepared with 3- N -Boc-5′- O -dimethoxytrityl-3′- O -nosyl-thymidine using the cartridge purification method. [ 18 F]FLT was prepared with a yield of 71%, and the product's purity was greater than 99%. Our results provide a new guideline for microscale [ 18 F]FLT radiosynthesis.

a b s t r a c t Objectives: To investigate quantitative methods of tumor proliferation using 3 � -( 18 F)fluoro-3 � - deoxythymidine ((18F)FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the ( 18 F)FLT-PET uptake with the Ki67 index. Material and methods: Thirty patients with newly diagnosed, untreated BC underwent a (18F)FLT-PET before and 14 days after bevacizumab treatment. A dynamic scan centered over the tumor began simulta- neously with the injection of (18F)FLT (385 ± 56 MBq). Image derived input functions were obtained using regions of interest drawn on the left ventricle (LV) and descending aorta (DA). Metabolite corrected blood curves were used as input functions to obtain the kinetic Ki constant using the Patlak graphical analysis (time interval 10-60 min after injection). Maximum SUV values were derived for the intervals 40-60 min (SUV40) and 50-60 min (SUV50). PET parameters were correlated with the Ki67 index obtained staining tumor biopsies. Results: ( 18 F)FLT uptake parameters decreased significantly (p < 0.001) after treatment: SUV50 = 3.09 ± 1.21 vs 2.22 ± 0.96; SUV40 = 3.00 ± 1.18 vs 2.14 ± 0.95, Ki LV(10-3) = 52(22-116) vs 38(13-80) and Ki DA(10-3) = 49(15-129) vs 33(11-98). Consistency interclass correlation coefficients within SUV and within Ki were high. Changes of SUV50 and Ki DA between baseline PET and after one bevacizumab dose PET correlated with changes in Ki67 index (r-Pearson = 0.35 and 0.26, p = 0.06 and 0.16, respectively). Conclusions: (18F)FLT-PET is useful to demonstrate proliferative changes after a dose of bevacizumab in patients with BC. Quantification of tumor proliferation by means of SUV and Ki has shown similar results, but SUV50 obtained better results. A correlation between (18F)FLT changes and Ki67 index was observed.

Objectives To investigate quantitative methods of tumor proliferation using 3′-[18F]fluoro-3′-deoxythymidine ([18F]FLT) PET in patients with breast cancer (BC), studied before and after one bevacizumab administration, and to correlate the [18F]FLT-PET uptake with the Ki67 index.

For noninvasive in vivo imaging of proliferation, 18F-FLT PET/CT remains a promising tool, owing to its correlation with proliferation indexes in many tumor entities. Future clinical applications will focus on monitoring response to cancer therapy, whereas tumor detection will be limited to organs with high physiologic 18F-FDG uptake. Use and interpretation of 18F-FLT requires knowledge of the physiologic tracer distribution and how it will be affected by anticancer treatment. Further studies are needed to determine the optimal timing of 18F-FLT PET/CT imaging in the course of cancer therapies or at the conclusion of therapy.

Background and purpose FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing 18F-FLT PET. Material and methods Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm] = 3.0 Gy), either daily or every second day. 18F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results. Results Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P 0.05) and 18 fractions in 36 days (P > 0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P 0.05). 18F-FLT parameters correlated strongly with proliferation markers (r2: 0.679–0.879, P Conclusions 18F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for 18F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.

18F-fluorothymidine (18F-FLT) is a radiolabeled thymidine analog that has been reported to help monitor tumor proliferation and has been studied in primary brain tumors; however, knowledge about 18F-FLT positron emission tomography/computed tomography (PET/CT) in metastatic brain lesions is limited. The purpose of this study is to evaluate the performance of 18F-FLT-PET/CT in metastatic brain lesions. A total of 20 PET/CT examinations (33 lesions) were included in the study. Semiquantitative analysis was performed: standard uptake value (SUV) with the utilization of SUVmax, tumor-to-background ratio (T/B), SUVpeak, SUV1cm3, SUV0.5cm3, SUV50%, SUV75%, PV50% (volume × SUV50%), and PV75% (volume × SUV75%) were calculated. Sensitivity, specificity, and accuracy for each parameter were calculated. Optimal cutoff values for each parameter were obtained. Using a receiver operating characteristic (ROC) curve analysis, the optimal cutoff values of SUVmax, T/B, and SUVpeak for discriminating active from non-active lesions were found to be 0.615, 4.21, and 0.425, respectively. In an ROC curve analysis, the area under the curve (AUC) is higher for SUVmax (p-value 0.017) compared to the rest of the parameters, while using optimal cutoff T/B shows the highest sensitivity and accuracy. PVs (proliferation × volumes) did not show any significance in discriminating positive from negative lesions. 18F-FLT-PET/CT can detect active metastatic brain lesions and may be used as a complementary tool. Further investigation should be performed.

As the preparation phase of a multicenter clinical trial using (18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), (18)F-fluoromisonidazole ((18)F-FMISO), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods.Ten (18)F-FDG, ten (18)F-FMISO, and ten (18)F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and κ. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV).For uptake intensity, the κ values between centers were, respectively, 0.59 for (18)F-FDG, 0.43 for (18)F-FMISO, and 0.44 for (18)F-FLT using the 5-level scale; the values were 0.81 for (18)F-FDG and 0.77 for both (18)F-FMISO and (18)F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for (18)F-FMISO and 0.2 and 0.3, respectively, for (18)F-FLT. The segmentation methods yielded significantly different volumes for (18)F-FMISO and (18)F-FLT (P0.001). In comparison with physicians, the best method found was 1.5 × maximum SUV (SUVmax) of the aorta for (18)F-FMISO and 1.3 × SUVmax of the muscle for (18)F-FLT. The methods using the SUV of 1.4 and the method using 1.5 × the SUVmax of the aorta could be used for (18)F-FMISO and (18)F-FLT. Moreover, for (18)F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6 × muscle SUVmax) could be used.The reproducibility of the visual analyses of (18)F-FMISO and (18)F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the (18)F-FMISO and (18)F-FLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased (18)F-FMISO or (18)F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4).

In order to establish early and precise methods for evaluating the effect of secondary chemotherapy in patients with recurrent ovarian cancer, both the clinical course of 3 women treated with gemcitabine-based secondary chemotherapy and the potential for early and accurate evaluation of the secondary chemotherapeutic effect of 18F-fluorothymidine (FLT) PET are reported. Standard uptake value with FLT PET decreased earlier than with 18F-fluorodeoxyglucose PET and was better correlated with a reduction in size as measured by CT. FLT PET could become a new standard for monitoring response to gemcitabine-based secondary chemotherapy treatment for recurrent ovarian cancer.

To investigate the effect of image-derived input functions (IDIF), input function corrections and volume of interest (VOI) size in quantification of [(18)F]FLT uptake in non-small cell lung cancer (NSCLC) patients.Twenty-three NSCLC patients were scanned on a HR+ scanner. IDIFs were defined over the aorta and left ventricle. Activity concentration and metabolite fraction were measured in venous blood samples. Venous blood samples at 30, 40 and 60 min after injection were used to calibrate the IDIF time-activity curves. Adaptive thresholds were used for VOI definition. Full kinetic analysis and simplified measures were performed.Non-linear regression analysis showed better fits for the irreversible model compared to the reversible model in the majority. Calibrated and metabolite corrected plus plasma-to-blood ratio corrected input function resulted in high correlations between SUV and Patlak K i (Pearson correlation coefficients 0.86-0.96, p value 0.001). No significant differences in correlation between SUV and Patlak K i were observed with variation of IDIF structure or VOI size.Plasma-to-blood ratio correction, metabolite correction and calibration improved the correlation between SUV and Patlak K i significantly, indicating the need for these corrections when K i is used to validate semi-quantitative measures, such as SUV.

Purpose The purpose of this prospective study was to clarify the value of FLT PET and FET PET for the noninvasive grading and prognosis of newly diagnosed gliomas. Materials and methods Twenty patients with newly diagnosed gliomas were investigated with FLT and FET PET before surgery. FLT and FET uptakes were assessed by the maximum standardized uptake (SUVmax) of tumor, and the ratio to uptake in the normal brain parenchyma (TNR). All tumors were graded by WHO system. Results FLT PET detected all 17 high-grade gliomas (HGG) and did not detect all 3 low-grade gliomas (LGG). FET PET detected all 20 HGG and LGG regardless of grading. The average FLT SUVmax in HGG and LGG was 1.51 ± 0.72 and 0.30 ± 0.07, and the average FLT TNR in HGG and LGG was 5.52 ± 3.09 and 1.12 ± 0.14, respectively. The differences of FLT SUVmax and TNR between HGG and LGG were statistically significant ( p = 0.0069, p = 0.0070). The average FET SUVmax in HGG and LGG was 2.68 ± 0.86 and 1.36 ± 0.15, and the average FET TNR in HGG and LGG was 2.31 ± 0.73 and 1.27 ± 0.12, respectively. The differences of FET SUVmax and TNR between HGG and LGG were statistically significant ( p = 0.0129, p = 0.0095). Conclusions FET PET has higher sensitivity in detection of gliomas rather than FLT PET, but it seems that FLT PET is better than FET PET for noninvasive grading and predicting prognosis of newly diagnosed gliomas, considering high contrast of FLT and overlap of FET uptakes between HGG and LGG.

This study compared the utility of 3'-deoxy-3'-(18)F-fluorothymidine PET ((18)F-FLT PET) with that of (18)F-FDG PET for assessment of the early locoregional clinical outcomes of chemoradiotherapy for head and neck squamous cell carcinomas.From May 2006 to September 2010, 28 patients with head and neck squamous cell carcinomas underwent (18)F-FLT and (18)F-FDG PET before radiation therapy (RT), 4 wk after the initiation of RT, and 5 wk after completion of RT. PET images were evaluated qualitatively for regions of focally increased metabolism and were analyzed in relation to residual accumulation and local disease control.During RT, (18)F-FLT uptake decreased more significantly than (18)F-FDG uptake. (18)F-FLT accumulations disappeared in 34 of 54 lesions (63%), and negative predictive value was 97%. (18)F-FDG PET during RT also had a high negative predictive value (100%), but only 9 lesions (16%) showed complete absence of accumulation. The specificity and overall accuracy of (18)F-FLT PET were significantly higher than those of (18)F-FDG PET both during and after RT. In particular, high significance was attributable to the results of the evaluations of primary lesions. There were significant differences in 3-y local control between the residual-accumulation and no-accumulation groups on both posttreatment (18)F-FLT PET (P0.0001) and posttreatment (18)F-FDG PET (P = 0.0081).(18)F-FLT PET during RT and early follow-up facilitates the selection of optimal further therapy and the prediction of outcomes.

Purpose Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3′-deoxy-3′-[18F]fluorothymidine (FLT) positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery.

OBJECTIVE The biological significance of [¹¹C]choline (CHO) uptake in human tumours is unclear and probably linked to choline kinase-α (CHKα) expression and cell proliferation. We directly compared CHO with [¹⁸F]fluorothymidine (FLT), an imaging biomarker of proliferation, by positron emission tomography (PET) in patients with breast cancer to investigate whether cell proliferation is an important determinant of CHO uptake. Furthermore, we evaluated CHKα and the Ki67-labelling index (LIKi67) in tumour biopsies. METHODS Sequential CHO-PET and FLT-PET within the same imaging session were performed in 21 patients with oestrogen receptor (ER)-positive breast cancer (28 lesions). Average and maximum CHO standardized uptake values (SUV) at 60 min: SUV60,av, and SUV60,max, and the rate constant of net irreversible uptake, Ki, were compared with FLT uptake at 60 min: SUV60,av and SUV60,max. Biopsies were stained for CHKα and LIKi67 in eight cases. RESULTS Tumours were equally visible on CHO-PET and FLT-PET imaging. Tumour CHO-PET strongly correlated with FLT imaging variables (Pearson's r=0.83; P

Purpose The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans. Methods and Materials Pre- and post-Week 1 treatment [18F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [18F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6–T7 vertebrae that straddled the field edge were measured for all patients. Results Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and Conclusions The change in SUV observed in head and neck cancer patients treated with chemoradiation shows the potential for using [18F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [18F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity.

OBJECTIVE: The aim of this study was to investigate the clinical value of 3'-deoxy-3'-[F]fluorothymidine-positron emission tomography/computed tomography (FLT-PET/CT) for lung cancer patients receiving carbon-ion radiotherapy. METHODS: Twenty consecutive patients with lung cancer underwent FLT-PET/CT before and after carbon-ion radiotherapy. Fifty minutes after intravenous injection of approximately 300 MBq of FLT, PET/CT data were acquired. Maximal standardized uptake value of the tumor was measured, from which the reduction rate of tumor FLT uptake was calculated. After treatment, the patients were followed (17-42 months for survivors) for the development of recurrence and survival. RESULTS: Primary responses to carbon-ion radiotherapy were partial in 13 patients, stable disease in six patients, and nonevaluable in one patient. Although tumor FLT uptake significantly decreased after treatment (P

OBJECTIVE We evaluated the diagnostic usefulness of 3'-deoxy-3'-[F]fluorothymidine (FLT) compared with 2-[F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in recurrent brain tumors. METHODS Twenty patients with suspected recurrence after surgical removal of primary tumors were studied. The uptake was assessed visually and quantified by standardized uptake value (SUV) and SUV ratio of tumor to white matter, tumor to gray matter, and tumor to normal tissue. Final diagnoses were made by histopathology or clinical and radiological follow-up. RESULTS Of 20 lesions, 15 were recurrences. 3'-Deoxy-3'-[F]fluorothymidine PET showed high diagnostic sensitivity (15/15 [100%]) and moderate specificity (3/5 [60.0%]). 2-[F]fluoro-2-deoxy-D-glucose PET showed moderate diagnostic sensitivity (11/15 [73.3%]) and specificity (4/5 [80%]). All of 4 recurrent tumors without FDG uptake showed FLT uptake. Tumor-to-normal tissue ratios (3.99 ± 1.72) of recurrent tumors on FLT PET were significantly higher than tumor-to-white matter ratios (1.96 ± 0.93) and tumor-to-gray matter ratios (1.32 ± 0.33) on FDG PET (P < 0.001), although SUVs (0.62 ± 0.32) of recurrent tumors on FLT PET were lower than those (2.44 ± 1.02) on FDG PET (P < 0.001). CONCLUSION 3'-Deoxy-3'-[F]fluorothymidine PET has a high sensitivity but a lower specificity, which has a limited role in the diagnosis of recurrent brain tumors as a complimentary tool of magnetic resonance imaging.

OBJECTIVE: Peritoneal metastasis (PM) is the most frequent form of metastasis in gastric cancer (GC). The sensitivity of detecting PM by pre-operative imaging modalities is low. Utility of positron emission tomography (PET) with (18)F-fluodeoxyglucose (FDG) for GC is limited, because diffuse-type tumors are not FDG-avid. (18)F-fluothymidine ([F-18]FLT) is a radiotracer that reflects cellular proliferation and the utility of [F-18]FLT-PET in GC has been reported. In this proof-of-concept study, we explored the ability of [F-18]FLT-PET/CT to detect PM of GC previously identified by other imaging modalities. METHODS: The key eligibility criteria were as follows; (i) histologically proven gastric adenocarcinoma; (ii) evident PM detected by CT performed within 4 weeks prior to registration; (iii) no prior treatment of PM within 4 weeks before registration. [F-18]FLT-PET/CT was performed at National Cancer Center Hospital, and [F-18]FLT-PET/CT images were evaluated independently by two radiologists. Safety assessments were carried out before and after [F-18]FLT-PET/CT. The primary end point was the detection sensitivity of PM. RESULTS: A total of 19 eligible patients were analyzed, of which 15 (78.9%) had diffuse-type histology. Detection sensitivity of PM, primary lesion, and lymph node metastasis were 73.7% [maximum standardized uptake value (SUVmax): 1.697–13.21], 100% (SUVmax: 2.71–22.01), and 72.7% (SUVmax: 2.079–12.61), respectively. No patients experienced adverse events during or after [F-18]FLT-PET/CT. CONCLUSION: This proof-of-concept study shows that [F-18]FLT-PET/CT is a sensitive method for detecting PM in GC, and paves the way for future studies investigating the clinical utility of this approach for the detection of clinically non-evident PM in GC. ADVANCES IN KNOWLEDGE: This proof-of-concept study found that [F-18]FLT-PET/CT is a sensitive method for detecting peritoneal metastases in GC.

Contains fulltext : 88322.pdf (Publisher’s version ) (Closed access) Accelerated tumor cell repopulation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. The noninvasive assessment of the proliferative state of a tumor by PET may provide a selection tool for customized treatment. 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a PET tracer that is phosphorylated by thymidine kinase 1 (TK-1) and, as such, reflects cellular proliferation. Before the use of (18)F-FLT PET for tumor characterization is accepted and introduced into clinical studies, validation against tumor histology is mandatory. The aim of this study was to validate (18)F-FLT PET in squamous cell carcinomas of the oral cavity using immunohistochemical staining for the proliferation marker iododeoxyuridine and for TK-1. METHODS: Seventeen patients with primary squamous cell carcinomas of the oral cavity underwent an (18)F-FLT PET/CT scan before surgery, and iododeoxyuridine was administered 20 min before tumor resection. (18)F-FLT PET/CT scans were segmented, and PET/CT volumes and PET signal intensities were calculated (mean standardized uptake value [SUV(mean)] and maximum standardized uptake value [SUV(max)]). Multiple paraffin-embedded tumor sections were immunohistochemically stained for iododeoxyuridine and TK-1. For iododeoxyuridine, labeling indices and optical densities were calculated and correlated with SUV(mean) and SUV(max). TK-1 staining was visually and semiquantitatively assessed. RESULTS: All primary tumors were identified with (18)F-FLT PET but with a large range in tracer uptake (mean SUV(max), 5.9; range, 2.2-15.2). Also, there was a large variability in iododeoxyuridine labeling indices (mean, 0.09; range, 0.01-0.29) and optical densities (mean, 28.2; range, 12.6-37.8). The iododeoxyuridine optical densities correlated significantly with SUV(mean) and SUV(max), but the labeling indices did not. In most tumors, TK-1 staining of varying intensity was present but correlated with neither iododeoxyuridine binding nor (18)F-FLT uptake. CONCLUSION: The current study demonstrated only a weak correlation between (18)F-FLT uptake and iododeoxyuridine staining intensity in oral cavity tumors. This weak correlation may be explained by differences in biomarker characteristics, resolution, and quantification methods. 01 mei 2010

Some new radiotracers might add useful information and improve diagnostic confidence of 18F-FDG imaging in tumors. A multicenter clinical trial was designed to investigate the diagnostic performance of dual-tracer (18F-FDG and 3′-deoxy-3′-18F-fluorothymidine [18F-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 18F-FDG and 18F-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 18F-FLT/18F-FDG standardized uptake value ratio of 0.4–0.90 was used as the threshold. Conclusion: By reflecting different biologic features, the dual-tracer PET/CT using 18F-FDG and 18F-FLT favorably affected the diagnosis of lung nodules.

The aim of this study was to evaluate the potential of (18)F-fluorothymidine (FLT) PET/CT for imaging pancreatic adenocarcinoma.This was a pilot study of five patients (four males, one female) with newly diagnosed and previously untreated pancreatic adenocarcinoma. Patients underwent FLT PET/CT, (18)F-fluorodeoxyglucose (FDG) PET/CT, and contrast-enhanced CT scanning before treatment. The presence of cancer was confirmed by histopathological analysis at the time of scanning in all five patients. The degree of FLT and FDG uptake at the primary tumor site was assessed using visual interpretation and semi-quantitative SUV analyses.The primary tumor size ranged from 2.5 x 2.8 cm to 3.5 x 7.0 cm. The SUV of FLT uptake within the primary tumor ranged from 2.1 to 3.1. Using visual interpretation, the primary cancer could be detected from background activity in two of five patients (40%) on FLT PET/CT. By comparison, FDG uptake was higher in each patient with a SUV range of 3.4 to 10.8, and the primary cancer could be detected from background in all five patients (100%).In this pilot study of five patients with primary pancreatic adenocarcinoma, FLT PET/CT scanning showed poor lesion detectability and relatively low levels of radiotracer uptake in the primary tumor.

OBJECTIVES The aim of this study was to compare the characteristics derived from fluorine-18 fluorodeoxyglucose (F-FDG) and fluorine-18 fluorothymidine (F-FLT) PET quantitatively and to assess their capacities during staging of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS Thirty-six patients with a diagnosis of ESCC who underwent both F-FDG and F-FLT PET were included in this study. Different image-derived indices including the standardized uptake value (SUV), gross tumor length, and texture features were determined. Considering histopathologic examination as the gold standard, the performance of the extracted indices during staging of ESCC was assessed using the Kruskal-Wallis test and the Mann-Whitney test. RESULTS Considering the F-FDG PET images, the SUVmax, SUVmean, length (LEN), and eccentricity (EC) were significant during staging of American Joint Committee on Cancer (AJCC) and TNM (P

Although 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a prospective radiopharmaceutical for the imaging of proliferating tumor cell, it is difficult to prepare large amount of [18F]FLT. We herein describe the preparation of [18F]FLT in an ionic liquid, [bmim][OTf] (1-butyl-3-methyl-imidazolium trifluoromethanesulfonate). At optimized condition, [18F]fluorinationin ionic liquid with 5 µl of 1 M KHCO3 and 5 mg of the precursor yielded 61.5 ± 4.3% (n=10). Total elapsed time was about 70 min including HPLC purification. The rapid synthesis of [18F]FLT can be achieved by removing all evaporation steps. Overall radiochemical yield and radiochemical purity were 30 ± 5% and >95%, respectively. This method can use a small amount of a nitrobenzenesulfonate precursor and can be adapted for automated production. Copyright © 2006 John Wiley & Sons, Ltd.

The aim of this study was to evaluate the use of [(18)F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2-T4) were studied by FLT-PET. For comparison, [(18)F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV(mean)=3.4+/-1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV(mean)=2.4+/-1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV(FLT): 3.2 vs SUV(FDG): 4.7 in primary tumours and SUV(FLT): 2.9 vs SUV(FDG): 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG ( P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.

We prepared 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) from 3'-O-nosyl thymidine derivative 3 or its pyrimidine ring N-BOC-protected analogue 5 and optimized [(18)F]fluorination condition for a high radiochemical yield. The optimal condition for [(18)F]fluorination with precursor 3 was 30 mg (41.1 micromol)/300 microl CH(3)CN at 130 degrees C for 5 min, while precursor 5 required 34 mg (40 micromol)/300 microl CH(3)CN at 110 degrees C for 5 min. After HPLC purification at neutral pH, we achieved high radiochemical yields of 40 +/- 5.2% and 42 +/- 5.4% (decay-corrected) within 60 min of preparation time with radiochemical purities of97%.

3'-deoxy-3'-18F-fluorothymidine ([(18)F] FLT) PET has been proven to be of value in diagnosis and assessment of glioma grading, in differentiating tumor recurrence from necrosis, in response assessment and in predicting overall survival (OS) in the primary high grade glioma. In this study, we evaluated the value of [(18)F] FLT PET-CT in predicting the OS of patients with recurrent malignant glioma.Fifty-six patients with recurrent malignant glioma were enrolled in this prospective study. The PET-CT and contrast-enhanced MRI scans were performed in all patients. Tumor volume was determined from both PET image (proliferative volume, PV) and MRI image (Vol-MRI). Patients were followed up clinically until death. The likelihood of using PET-derived parameters of SUVmax, tumor-to-normal (T/N) ratio, and PV to predict the OS of patients were assessed in comparison with Vol-MRI and other clinical parameters.The follow up periods for all patients ranged from 1.5 to 35.6 months with median of 9.8 months. Univariate analysis showed that the following parameters were significantly correlated with OS: grade of primary tumor (p=0.042), Karnofsky performance score (KPS) (p=0.041), T/N ratio (p0.01), Vol-MRI (p=0.041), and PV (p0.001). However, multivariate Cox regression showed that only the PV (p0.001) and T/N ratio (p=0.001) were independent predictors. The thresholds to predict OS were 16.88 cm(3) for PV and 10.94 for T/N ratio. Kaplan-Meier analyses using these thresholds showed a significant discrimination between short and long OS groups (p0.001).The PV and T/N ratio of tumor on [(18)F] FLT PET-CT are independent predictors of survival in patients with recurrent malignant glioma. The PV on [(18)F] FLT PET seems to be more predictive than tumor volume on T1-weighted MRI for OS.

The purpose of this study was to evaluate the consistency of 3'-deoxy-3'[(18)F]fluorothymidine (FLT) standardized uptake values (SUVs) over the time course of imaging in head and neck cancer. Thirteen (13) subjects (all male; age: 56.9 +/- 6.7 years) with squamous cell head and neck cancer, stage III/IV, were administered FLT and imaged dynamically for 1 hour over the tumor and then underwent whole-body (WB) imaging commencing at 74 +/- 6 minutes. Imaging was repeated after 5 days of radiotherapy (10 Gy) and a single course of platinum-based chemotherapy. Volumes-of-interest (VOIs) were created on the last dynamic frame (SUV(60)). The pretherapy WB and midtherapy images were coregistered to the dynamic sequence and VOIs were applied. Mean and maximum SUVs (SUV(60) and SUV(WB)) and the change with treatment were evaluated. The correlations (Spearman's rho) between SUV(60) and SUV(WB) for all VOIs (pre- and midtherapy, n = 108 data pairs) were 0.98 for mean and 0.97 for maximum SUVs (p0.0001). Average absolute differences between SUV(60) and SUV(WB) were 0.18 +/- 0.15 and 0.29 +/- 0.32 SUV units, respectively. Correlations (Spearman's rho) between the change in SUV with therapy were 0.90 for mean and 0.89 for maximum SUV (p0.0001), with differences in the change values averaging 0.03 +/- 0.36 and -0.17 +/- 0.57 units, respectively. FLT SUVs are stable and comparable for images initiated between 55 and 100 minutes postinjection whether acquired pre- or midtherapy in head and neck cancer.

[18F]FLT (3′-deoxy-3′-[18F]fluorothymidine) turned out to be a tracer particularly suitable for PET imaging of tumor proliferation because of lacking degradation in vivo. To facilitate clinical studies with [18F]FLT, we investigated two new easily accessible precursors, 2,3′-anhydrothymidine (AThy) and 5′-O-(4,4′-dimethoxytriphenylmethyl)-2,3′-anhydrothymidine (DMTThy), using a common approach for introducing the label with nucleophilic [18F]fluoride. Radiochemical yields were determined in dependence on substrate concentration, reaction time and temperature. In the case of AThy (10 mg), best FLT yields were 5.3%±1.2 (130 °C, 30 min). Labeling of DMTThy (10 mg) gave 14.3%±3.3 at 160 °C within 10 minutes. Starting with an aqueous solution of 20 GBq [18F]fluoride the new method allows to produce 1.3 GBq [18F]FLT within 90 minutes ready for intravenous injection. The new labeling procedures allow [18F]FLT synthesis without lengthy preparation of the precursor and with high reproducibility mandatory for clinical application.

High-yielding, automated production of a PET tracer that reflects proliferation, 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), is reported using a modified Bioscan Coincidence FDG reaction module.Production of [(18)F]FLT was implemented through: (1) modification of an original FDG manifold; (2) application of an alternate time sequence; and (3) altered solid-phase extraction (SPE) purification. Quality control testing, including standard radiochemical figures of merit and preclinical positron emission tomography (PET) imaging, was carried out.High decay-corrected yields of [(18)F]FLT (16-39%) were reproducibly obtained. The product exhibited very high specific activity (4586.9TBq/mmol; 123,969Ci/mmol) and radiochemical purity (99%). Overall, the [(18)F]FLT produced in this manner was superior to typical productions that utilized a GE TRACERlab FXF-N reaction module. Additionally, purification with SPE cartridges, followed by manual elution, accelerated overall run time and resulted in a two-fold increase in [(18)F]FLT concentration. PET imaging showed the [(18)F]FLT produced by this method was highly suitable for non-invasive tumor imaging in mice.The Bioscan Coincidence GE FDG Reaction Module was readily adapted to reproducibly provide [(18)F]FLT in high yield, specific activity, and radiochemical purity. The approach was suitable to provide sufficient amounts of material for preclinical studies.

Purpose Changes 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. Methods Sixteen 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. Results In 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

The aim of this analysis was to evaluate a new visual scoring scale developed to facilitate the qualitative appraisal of lesion uptake on (18)F-fluorothymidine PET ((18)F-FLT-PET).Sixty-two patients with a pulmonary lesion of unknown aetiology who had undergone an F-fluorodeoxyglucose-PET/computed tomography (CT) suspicious for malignancy prospectively underwent an (18)F-FLT-PET/CT. Three nuclear medicine physicians independently reviewed each (18)F-FLT-PET/CT scan with knowledge of the location of the pulmonary lesion but blinded to the final diagnosis. They scored the lesion (18)F-FLT uptake as follows: (0) no visible uptake; (1)spleen; (2) ≥ spleen, butboth liver and marrow; (3) between liver and marrow; (4)liver andmarrow. Lesion mean (SUV(mean)) and maximum (SUV(max)) standardized uptake values were measured in a separate session.In all, 35 lesions were malignant and 27 were benign, as assessed on the basis of surgery, biopsy or follow-up of at least 12 months. Visual score, SUV(mean) and SUV(max) were statistically different between benign and malignant lesions. The visual scoring scale showed substantial to almost-perfect interobserver agreement with a weighted κ value of 0.84, 0.67 and 0.65 for each observer pair. The visual score was highly correlated to SUV(mean) and SUV(max) (r=0.83 and 0.87, respectively) and described a logarithmic pattern in relation to SUV(mean) and SUV(max) (r =0.67 and 0.72, respectively). The area under the receiver-operating characteristic curve for the visual score was 0.86 and was statistically different from that for SUV(mean) (0.77; P=0.026) and SUV(max) (0.79; P=0.047).The (18)F-FLT scoring scale we propose is easy to use with high interobserver agreement and a significantly better discriminative capacity compared with SUV measurements. It has the potential to harmonize the qualitative interpretation of (18)F-FLT-PET/CT in lung cancer diagnosis.

Intra-tumour heterogeneity is a characteristic shared by all cancers. We explored the use of texture variables derived from images of [(18)F]fluorothymidine-positron emission tomography (FLT-PET), thus notionally assessing the heterogeneity of proliferation in individual tumours. Our aims were to study the range of textural feature values across tissue types, verify the repeatability of these image descriptors and further, to explore associations with clinical response to chemotherapy in breast cancer patients. The repeatability of 28 textural descriptors was assessed in patients who had two FLT-PET scans prior to therapy using relative differences and the intra-class correlation coefficient (ICC). We tested associations between features at baseline and clinical response measured in 11 patients after three cycles of chemotherapy, and explored changes in FLT-PET at one week after the start of therapy. A subset of eight features was characterized by low variations at baseline (±30%) and high repeatability (0.7 ≤ ICC ≤ 1). The intensity distribution profile suggested fewer highly proliferating cells in lesions of non-responders compared to responders at baseline. A true increase in CV and homogeneity was measured in four out of six responders one week after the start of therapy. A number of textural features derived from FLT-PET are altered following chemotherapy in breast cancer, and should be evaluated in larger clinical trials for clinical relevance.

We report an invasive thymoma discovered incidentally by an 18F-FLT (fluorothymidine) PET study on a 48-year-old woman. The patient had equivocal breast lesions in her bilateral breasts. She entered a clinical 18F-FLT PET trial in our hospital to differentiate malignant breast tumors from benign ones. No 18F FLT-avid lesions in her breasts were revealed. But an intense 18F-FLT uptake lesion was noted in her right anterior mediastinum. However, an F-FDG PET scan showed only mild F-FDG uptake in the lesion. Video-assisted thoracic surgery thymectomy was subsequently performed, and the final pathology showed invasive thymoma.

Although [(18)F]fluorothymidine positron emission tomography (FLT-PET) permits estimation of tumor thymidine kinase-1 expression, and thus, cell proliferation, high physiological uptake of tracer in liver tissue can limit its utility. We evaluated FLT-PET combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT-PET(KSF)) for detecting drug response in liver metastases. FLT-PET and computed tomography data were collected from patients with confirmed breast or colorectal liver metastases before, and two weeks after the first cycle of chemotherapy. Changes in tumor FLT-PET and FLT-PET(KSF) variables were determined. Visual distinction between tumor and normal liver was seen in FLT-PET(KSF) images. Of the 33 metastases from 20 patients studied, 26 were visible after kinetic filtering. The net irreversible retention of the tracer (Ki; from unfiltered data) in the tumor, correlated strongly with tracer uptake when the imaging variable was an unfiltered average or maximal standardized uptake value, 60 min post-injection (SUV(60,av): r = 0.9, SUV(60,max): r = 0.7; p0.0001 for both) and occurrence of high intensity voxels derived from FLT-PET(KSF) (r = 0.7, p0.0001). Overall, a significant reduction in the imaging variables was seen in responders compared to non-responders; however, the two week time point selected for imaging was too early to allow prediction of long term clinical benefit from chemotherapy. FLT-PET and FLT-PET(KSF) detected changes in proliferation in liver metastases.