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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

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.

Background: Pulmonary vascular cell hyperproliferation is characteristic of pulmonary vascular remodeling in pulmonary arterial hypertension. A noninvasive imaging biomarker is needed to track the pathology and assess the response to novel treatments targeted at resolving the structural changes. Here, we evaluated the application of radioligand 3′-deoxy-3′-[18F]-fluorothymidine ( 18 FLT) using positron emission tomography. Methods and Results: We performed dynamic 18 FLT positron emission tomography in 8 patients with idiopathic pulmonary arterial hypertension (IPAH) and applied in-depth kinetic analysis with a reversible 2-compartment 4k model. Our results show significantly increased lung 18 FLT phosphorylation (k 3 ) in patients with IPAH compared with nonpulmonary arterial hypertension controls (0.086±0.034 versus 0.054±0.009 min −1 ; P 18 FLT signal both between patients with IPAH and within the lungs of each patient, compatible with histopathologic reports of lungs from patients with IPAH. Consistent with 18 FLT positron emission tomographic data, TK1 (thymidine kinase 1) expression was evident in the remodeled vessels in IPAH patient lung. In addition, hyperproliferative pulmonary vascular fibroblasts isolated from patients with IPAH exhibited upregulated expression of TK1 and the thymidine transporter, ENT1 (equilibrative nucleoside transporter 1). In the monocrotaline and SuHx (Sugen hypoxia) rat pulmonary arterial hypertension models, increased lung 18 FLT uptake was strongly associated with peripheral pulmonary vascular muscularization and the proliferation marker, Ki-67 score, together with prominent TK1 expression in remodeled vessels. Importantly, lung 18 FLT uptake was attenuated by 2 antiproliferative treatments: dichloroacetate and the tyrosine kinase inhibitor, imatinib. Conclusions: Dynamic 18 FLT positron emission tomography imaging can be used to report hyperproliferation in pulmonary hypertension and merits further study to evaluate response to treatment in patients with IPAH.

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.

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

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.