Monolithic integration of polymer waveguide phase modulators with silicon nitride waveguides using adiabatic transition tapers.

Polymer waveguide phase modulators (PMs) demonstrate high thermal confinement with outstanding thermo-optic properties and can provide stable low-power phase modulation in optical phased arrays (OPA). On the other hand, silicon nitride (SiN) waveguides produce stronger optical confinement with smaller waveguide core sizes than polymer waveguides and can handle high optical power without nonlinear effects. In this work, a high-performance PM was achieved by monolithic integration of a polymer waveguide and tapered SiN input and output waveguides. The integration of heterogeneous waveguide materials on a single substrate will enable the fabrication of efficient OPAs for advanced imaging, display, sensing, and communications applications.

High-performance optical phased array for LiDARs demonstrated by monolithic integration of polymer and SiN waveguides.

Optical phased array (OPA) beam scanners for light detection and ranging (LiDAR) are proposed by integrating polymer waveguides with superior thermo-optic effect and silicon nitride (SiN) waveguides exhibiting strong modal confinement along with high optical power capacity. A low connection loss of only 0.15 dB between the polymer and SiN waveguides was achieved in this work, enabling a low-loss OPA device. The polymer-SiN monolithic OPA demonstrates not only high optical throughput but also efficient beamforming and stable beam scanning. This novel integrative approach highlights the potential of leveraging heterogeneous photonic materials to develop advanced photonic integrated circuits with superior performance.

Fast-running beamforming algorithm for optical phased array beam scanners comprised of polymeric waveguide devices.

The phase error imposed in optical phased arrays (OPAs) for beam scanning LiDAR is unavoidable due to minute dimensional fluctuations that occur during the waveguide manufacturing process. To compensate for the phase error, in this study, a fast-running beamforming algorithm is developed based on the rotating element vector method. The proposed algorithm is highly suitable for OPA devices comprised of polymer waveguides, where thermal crosstalk between phase modulators is suppressed effectively, allowing for each phase modulator to be controlled independently. The beamforming speed is determined by the number of phase adjustments. Hence, by using the least square approximation for a 32-channel polymer waveguide OPA device the number of phase adjustments needed to complete beamforming was reduced and the beamforming time was shortened to 16 seconds.

Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.

Cross-section measurements for 68Zn(p,2p)67Cu and 68Zn(p,2n)67Ga reactions using a newly developed separation method for the superposed [Formula: see text]-ray spectra.

We have developed a new analytical peak separation analysis for superposed [Formula: see text]-ray peaks on [Formula: see text]Cu and [Formula: see text]Ga to measure the [Formula: see text]Zn(p,2p)[Formula: see text]Cu and [Formula: see text]Zn(p,2n)[Formula: see text]Ga reactions, unlike in most previous works that were employing a radiochemical separation to measure them. Based on the nuclear data such as the [Formula: see text]-ray intensity and the half-life for each nuclide, we may develop a new analytical method that enables us to estimate the respective counts arising from each nuclide, thereby obtaining the nuclear reactions. The newly developed analytical method can universally be applied to separate the superposed [Formula: see text]-ray spectra of any two nuclides, especially superior in separating the nuclides with different half-lives. In comparison with the data in the literature, the two reactions in the present work are in good agreement with those of some previous works. In addition, we compared the present [Formula: see text]Zn(p,2n)[Formula: see text]Ga reaction without the peak separation to the data in the literature without the chemical separation, and find that a good agreement is evident, enhancing the reliability of the [Formula: see text]Zn(p,x)[Formula: see text]Zn and [Formula: see text]Zn(p,3n)[Formula: see text]Ga reactions, which are further measured in the present work.

Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 That Exhibits Antiviral Efficacy in SARS-CoV-2-Infected African Green Monkeys.

Remdesivir 1 is an phosphoramidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells, thereby forming the bioactive triphosphate 2-NTP. 2-NTP, an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for 1 have prompted interest in oral approaches to generate 2-NTP. Here, we describe the discovery of a 5'-isobutyryl ester prodrug of 2 (GS-5245, Obeldesivir, 3) that has low cellular cytotoxicity and 3-7-fold improved oral delivery of 2 in monkeys. Prodrug 3 is cleaved presystemically to provide high systemic exposures of 2 that overcome its less efficient metabolism to 2-NTP, leading to strong SARS-CoV-2 antiviral efficacy in an African green monkey infection model. Exposure-based SARS-CoV-2 efficacy relationships resulted in an estimated clinical dose of 350-400 mg twice daily. Importantly, all SARS-CoV-2 variants remain susceptible to 2, which supports development of 3 as a promising COVID-19 treatment.

Frequency Response of Thermo-Optic Phase Modulators Based on Fluorinated Polyimide Polymer Waveguide.

Polymer waveguide phase modulators exhibit stable low-power phase modulation owing to their exceptional thermal confinement and high thermo-optic effect, and thus, have the merit of thermal isolation between channels, which is crucial for an optical phased array (OPA) beam scanner device. In this work, a waveguide phase modulator was designed and fabricated based on a high-refractive-index fluorinated polyimide. The propagation loss of the polyimide waveguide and the temporal response of the phase modulator were characterized. Moreover, the transfer function of the phase modulator including multiple poles and zeros was obtained from the measured frequency response. The polyimide waveguide modulator device demonstrated a fast response time of 117 µs for 1 kHz input signal, however, for 1 mHz step-function input, it exhibited an additional 5% phase change in 5 s.

Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice.

The coronavirus disease 2019 (COVID-19) pandemic remains uncontrolled despite the rapid rollout of safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. In addition, the emergence of SARS-CoV-2 variants of concern, with their potential to escape neutralization by therapeutic monoclonal antibodies, emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parent nucleoside of remdesivir, which targets the highly conserved virus RNA-dependent RNA polymerase. GS-621763 exhibited antiviral activity against SARS-CoV-2 in lung cell lines and two different human primary lung cell culture systems. GS-621763 was also potently antiviral against a genetically unrelated emerging coronavirus, Middle East respiratory syndrome CoV (MERS-CoV). The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 administration reduced viral load and lung pathology; treatment also improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral that has recently received EUA approval, proved both drugs to be similarly efficacious in mice. These data support the exploration of GS-441524 oral prodrugs for the treatment of COVID-19.

Compact solid-state optical phased array beam scanners based on polymeric photonic integrated circuits.

Optical phased array (OPA) devices are being actively investigated to develop compact solid-state beam scanners, which are essential in fields such as LiDAR, free-space optical links, biophotonics, etc. Based on the unique nature of perfluorinated polymers, we propose a polymer waveguide OPA with the advantages of low driving power and high optical throughput. Unlike silicon photonic OPAs, the polymer OPAs enable sustainable phase distribution control during beam scanning, which reduces the burden of beamforming. Moreover, by incorporating a tunable wavelength laser comprising a polymer waveguide Bragg reflector, two-dimensional beam scanning is demonstrated, which facilitates the development of laser-integrated polymeric OPA beam scanners.

Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice.

The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective SARS-CoV-2 vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. Additionally, the emergence of SARS-CoV-2 variants of concern with their potential to escape therapeutic monoclonal antibodies emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parental nucleoside of remdesivir, which targets the highly conserved RNA-dependent RNA polymerase. GS-621763 exhibited significant antiviral activity in lung cell lines and two different human primary lung cell culture systems. The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 significantly reduced viral load, lung pathology, and improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral currently in human clinical trial, proved both drugs to be similarly efficacious. These data demonstrate that therapy with oral prodrugs of remdesivir can significantly improve outcomes in SARS-CoV-2 infected mice. Thus, GS-621763 supports the exploration of GS-441524 oral prodrugs for the treatment of COVID-19 in humans.

Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets.

Remdesivir is an antiviral approved for COVID-19 treatment, but its wider use is limited by intravenous delivery. An orally bioavailable remdesivir analog may boost therapeutic benefit by facilitating early administration to non-hospitalized patients. This study characterizes the anti-SARS-CoV-2 efficacy of GS-621763, an oral prodrug of remdesivir parent nucleoside GS-441524. Both GS-621763 and GS-441524 inhibit SARS-CoV-2, including variants of concern (VOC) in cell culture and human airway epithelium organoids. Oral GS-621763 is efficiently converted to plasma metabolite GS-441524, and in lungs to the triphosphate metabolite identical to that generated by remdesivir, demonstrating a consistent mechanism of activity. Twice-daily oral administration of 10 mg/kg GS-621763 reduces SARS-CoV-2 burden to near-undetectable levels in ferrets. When dosed therapeutically against VOC P.1 gamma γ, oral GS-621763 blocks virus replication and prevents transmission to untreated contact animals. These results demonstrate therapeutic efficacy of a much-needed orally bioavailable analog of remdesivir in a relevant animal model of SARS-CoV-2 infection.

Prodrugs of a 1'-CN-4-Aza-7,9-dideazaadenosine C-Nucleoside Leading to the Discovery of Remdesivir (GS-5734) as a Potent Inhibitor of Respiratory Syncytial Virus with Efficacy in the African Green Monkey Model of RSV.

A discovery program targeting respiratory syncytial virus (RSV) identified C-nucleoside 4 (RSV A2 EC50 = 530 nM) as a phenotypic screening lead targeting the RSV RNA-dependent RNA polymerase (RdRp). Prodrug exploration resulted in the discovery of remdesivir (1, GS-5734) that is >30-fold more potent than 4 against RSV in HEp-2 and NHBE cells. Metabolism studies in vitro confirmed the rapid formation of the active triphosphate metabolite, 1-NTP, and in vivo studies in cynomolgus and African Green monkeys demonstrated a >10-fold higher lung tissue concentration of 1-NTP following molar normalized IV dosing of 1 compared to that of 4. A once daily 10 mg/kg IV administration of 1 in an African Green monkey RSV model demonstrated a >2-log10 reduction in the peak lung viral load. These early data following the discovery of 1 supported its potential as a novel treatment for RSV prior to its development for Ebola and approval for COVID-19 treatment.

Synthesis and evaluation of cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[(124)I]iodouracil: a new potential PET imaging agent for HSV1-tk expression.

In our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (HSV1-tk), a carbocyclic nucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[124I]iodouracil, has been efficiently synthesized. A Pd(0)-catalyzed coupling reaction together with organotin and exchange reactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemical purity and 1.15 GBq/mumol specific activity. Biological data reveal that the analogue is stable in vitro, less toxic than ganciclovir (GCV), and selective to HSV1-tk-expressed cells based on micro positron emission tomography (microPET) image analyses. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5-iodouridine (carbocyclic d4IU) is a potential imaging probe for HSV1-tk.

Synthesis and biologic evaluation of I-123-labeled porphyrin derivative as a potential tumor-imaging agent.

5-(3-(3-[(123)I]iodoallyloxy)phenyl)-10,15,20-tris-(3-carboxymethoxyphenyl)porphyrin ([ (123)I]2) was prepared for biologic evaluation in a B16-F10 tumor model to examine its potential as an imaging agent. The I-123-labeled porphyrin [(123)I]2 was purified by reverse-phase high-performance liquid chromatography (HPLC) to give a decay-corrected radiochemical yield of 8%-13% (n=9) and the radiochemical purity after HPLC purification was >95% and the overall radiolabeling time was 160 minutes. The in vitro cell uptake of [ (123)I]2 increased with time. Biodistribution in mice bearing the B16-F10 tumor, after an intravenous injection of [(123)I]2, also showed a time-dependent accumulation of the porphyrin in tumor tissue (10.35 %ID/g at 6 hours). The tumor-to-muscle ratio was 3.49, 3.38, 3.07, and 3.13 at 1, 2, 6, and 24 hours, respectively. The gamma-camera images of (123)I-porphyrin demonstrated a high focal accumulation of radioactivity in the B16-F10 melanoma tumor.

Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.

The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.

Anatomical morphometric study of the cervical uncinate process and surrounding structures.

OBJECTIVE: The purpose of this study is to elucidate the anatomic relationships between the uncinate process and surrounding neurovascular structures to prevent possible complications in anterior cervical surgery. METHODS: Twenty-eight formalin-fixed cervical spines were removed from adult cadavers and were studied. The authors investigated the morphometric relationships between the uncinate process, vertebral artery and adjacent nerve roots. RESULTS: The height of the uncinate process was 5.6-7.5 mm and the width was 5.8-8.0 mm. The angle between the posterior tip of the uncinate process and vertebral artery was 32.2-42.4°. The distance from the upper tip of the uncinate process to the vertebral body immediately above was 2.1-3.3 mm, and this distance was narrowest at the fifth cervical vertebrae. The distance from the posterior tip of the uncinate process to the nerve root was 1.3-2.0 mm. The distance from the uncinate process to the vertebral artery was measured at three different points of the uncinate process : upper-posterior tip, lateral wall and the most antero-medial point of the uncinate process, and the distances were 3.6-6.1 mm, 1.7-2.8 mm, and 4.2-5.7 mm, respectively. The distance from the uncinate process tip to the vertebral artery and the angle between the uncinate process tip and vertebral artery were significantly different between the right and left side. CONCLUSION: These data provide guidelines for anterior cervical surgery, and will aid in reducing neurovascular injury during anterior cervical surgery, especially in anterior microforaminotomy.

Morphometric Relationship between the Cervicothoracic Cord Segments and Vertebral Bodies.

OBJECTIVE: The objective of this study was to investigate the morphologic characteristics between the vertebral body and the regions of the cervical and thoracic spinal cords where each rootlets branch out. METHODS: Sixteen adult cadavers (12 males and 4 females) with a mean age of 57.9 (range of 33 to 70 years old) were used in this study. The anatomical relationship between the exit points of the nerve roots from the posterior root entry zone at each spinal cord segment and their corresponding relevant vertebral bodies were also analyzed. RESULTS: Vertical span of the posterior root entry zone between the upper and lower rootlet originating from each spinal segment ranged from 10-12 mm. The lengths of the rootlets from their point of origin at the spinal cord to their entrance into the intervertebral foramen were 5.9 mm at the third cervical nerve root and increased to 14.5 mm at the eighth cervical nerve root. At the lower segments of the nerve roots (T3 to T12), the posterior root entry zone of the relevant nerve roots had a corresponding anatomical relationship with the vertebral body that is two segments above. The posterior root entry zones of the sixth (94%) and seventh (81%) cervical nerve roots were located at a vertebral body a segment above from relevant segment. CONCLUSION: Through these investigations, a more accurate diagnosis, the establishment of a better therapeutic plan, and a decrease in surgical complications can be expected when pathologic lesions occur in the spinal cord or vertebral body.

Comparison of cell-labeling methods with ¹²4I-FIAU and 64Cu-PTSM for cell tracking using chronic myelogenous leukemia cells expressing HSV1-tk and firefly luciferase.

Cell-tracking methods with molecular-imaging modality can monitor the biodistribution of cells. In this study, the direct-labeling method with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (64Cu-PTSM), indirect cell-labeling methods with herpes simplex virus type 1-thymidine kinase (HSV1-tk)-mediated ¹²4I-2'-fluoro-2'-deoxy-1-ß-D-arabinofuranosyl-5-iodouracil (¹²4I-FIAU) were comparatively investigated in vitro and in vivo for tracking of human chronic myelogenous leukemia cells. K562-TL was established by retroviral transduction of the HSV1-tk and firefly luciferase gene in the K562 cell. K562-TL cells were labeled with 64Cu-PTSM or ¹²4I-FIAU. Cell labeling efficiency, viability, and radiolabels retention were compared in vitro. The biodistribution of radiolabeled K562-TL cells with each radiolabel and small-animal positron emission tomography imaging were performed. Additionally, in vivo and ex vivo bioluminescence imaging (BLI) and tissue reverse transcriptase-polymerase chain reaction (RT-PCR) analysis were used for confirming those results. K562-TL cells were efficiently labeled with both radiolabels. The radiolabel retention (%) of ¹²4I-FIAU (95.2%±1.1%) was fourfold higher than 64Cu-PTSM (23.6%±0.7%) at 24 hours postlabeling. Viability of radiolabeled cells was statistically nonsignificant between ¹²4I-FIAU and 64Cu-PTSM. The radioactivity of each radiolabeled cells was predominantly accumulated in the lungs and liver at 2 hours. Both the radioactivity of 64Cu-PTSM- and ¹²4I-FIAU-labeled cells was highly accumulated in the liver at 24 hours. However, the radioactivity of ¹²4I-FIAU-labeled cells was markedly decreased from the body at 24 hours. The K562-TL cells were dominantly localized in the lungs and liver, which also verified by BLI and RT-PCR analysis at 2 and 24 hours postinjection. The 64Cu-PTSM-labeled cell-tracking method is more efficient than ¹²4I-FIAU-labeled cell tracking, because of markedly decrease of radioactivity and fast efflux of ¹²4I-FIAU in vivo. In spite of a high labeling yield and radiolabel retention of ¹²4I-FIAU in vitro, the in vivo cell-tracking method using 64Cu-PTSM could be a useful method to evaluate the distribution and targeting of various cell types, especially, stem cells and immune cells.

The Changes in Range of Motion after a Lumbar Spinal Arthroplasty with Charité in the Human Cadaveric Spine under Physiologic Compressive Follower Preload : A Comparative Study between Load Control Protocol and Hybrid Protocol.

OBJECTIVE: To compare two testing protocols for evaluating range of motion (ROM) changes in the preloaded cadaveric spines implanted with a mobile core type Charité lumbar artificial disc. METHODS: Using five human cadaveric lumbosacral spines (L2-S2), baseline ROMs were measured with a bending moment of 8 Nm for all motion modes (flexion/extension, lateral bending, and axial rotation) in intact spine. The ROM was tracked using a video-based motion-capturing system. After the Charité disc was implanted at the L4-L5 level, the measurement was repeated using two different methods : 1) loading up to 8 Nm with the compressive follower preload as in testing the intact spine (Load control protocol), 2) loading in displacement control until the total ROM of L2-S2 matches that when the intact spine was loaded under load control (Hybrid protocol). The comparison between the data of each protocol was performed. RESULTS: The ROMs of the L4-L5 arthroplasty level were increased in all test modalities (p < 0.05 in bending and rotation) under both load and hybrid protocols. At the adjacent segments, the ROMs were increased in all modes except flexion under load control protocol. Under hybrid protocol, the adjacent segments demonstrated decreased ROMs in all modalities except extension at the inferior segment. Statistical significance between load and hybrid protocols was observed during bending and rotation at the operative and adjacent levels (p < 0.05). CONCLUSION: In hybrid protocol, the Charité disc provided a relatively better restoration of ROM, than in the load control protocol, reproducing clinical observations in terms of motion following surgery.

Comparison of 18F-FDG, 18F-FET and 18F-FLT for differentiation between tumor and inflammation in rats.

INTRODUCTION: The goal of this study was to compare the glucose analog, 2-[18F]fluoro-2-deoxy-d-glucose ([18F]-FDG), the amino acid analog, o-(2-[18F]fluoroethyl)-l-tyrosine ([18F]-FET) and nucleoside analog, 3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) with regard to their feasibility for differentiating tumors from inflammation. METHODS: In Fisher rat models bearing both 9L tumor and inflammation, the biodistributions and positron emission tomography (PET) images of [18F]-FDG, [18F]-FET and [18F]-FLT at 60 min post injection were compared. Pretreatment with thymidine phosphorylase before injection of [18F]-FLT was performed. RESULTS: The tumor-to-blood (T/B) and tumor-to-muscle (T/M) ratios of [18F]-FDG were significantly higher than those of [18F]-FET and [18F]-FLT (P<.01); however, the accumulation of [18F]-FDG [1.23+/-0.52 percent injected dose per gram of tissue (%ID/g)] in inflammation was also elevated. T/B and T/M ratios of [18F]-FET (2.3+/-0.5 and 2.2+/-0.5) were higher than those of [18F]-FLT (1.6+/-0.6 and 1.6+/-0.5), and inflammation uptake of those tracers was very low (0.63+/-0.19 and 0.27+/-0.16 %ID/g, respectively). [18F]-FET and [18F]-FLT showed higher selectivity indices (tumor-to-inflammation ratio corrected background) than [18F]-FDG. In PET images, [18F]-FDG was found to be accumulated in both tumor and inflammation, but [18F]-FET and [18F]-FLT selectively localized in tumor. CONCLUSION: Our data confirm the result of previous studies that [18F]-FET and [18F]-FLT are superior to [18F]-FDG in differentiating tumor from inflammation.