ライフサイエンスコーパス: FIAU

1 FIAU accumulation at 24 h was 1.53 +/- 0.40 %dose/g.

2 FIAU and FMAU disrupted mitochondria and caused accumula

3 FIAU is of interest as a potential reporter probe to mon

4 FIAU is readily extended by the next correct base pair (

5 FIAU was found to inhibit the growth of WT Escherichia c

6 FIAU-induced liver toxicity could be readily detected us

7 in vitro or in vivo with [131I]FIAU or [124I]FIAU can be noninvasively tracked in SCID mice bearing h

8 tivity and resolution is expected with [124I]FIAU and PET.

9 uoro-1-beta-D-arabinofuranosyluracil ([124I]-FIAU) and positron emission tomography (PET) and the abi

10 ing radiolabeled 2'-fluoro-nucleoside [124I]-FIAU and a clinical PET system.

11 ant relationship between the level of [124I]-FIAU accumulation [% injected dose/g and incorporation c

12 Highly specific images of [124I]-FIAU-derived radioactivity were obtained in W256TK* tumo

13 rst set, we tested the sensitivity of [124I]-FIAU-PET imaging to detect low levels of HSV1-tk gene ex

14 n tomography (PET) and the ability of [124I]-FIAU-PET imaging to discriminate different levels of HSV

15 In the second set, we tested whether [124I]-FIAU and PET imaging can measure and discriminate betwee

16 arabinofuranosyl)-5-[125I] iodouracil ([125I]FIAU) within bacteria.

17 bacteria could be readily imaged with [125I]FIAU.

18 mors confirmed that the high levels of [131I]FIAU-derived radioactivity (> 1% dose) were localized to

19 ontrast, significantly lower levels of [131I]FIAU-derived radioactivity (< 0.01%) were observed in th

20 The level of [131I]FIAU-derived radioactivity accumulation (HSV1-tk express

21 There was no accumulation of [131I]FIAU-derived radioactivity in tumors that were injected

22 vealed highly specific localization of [131I]FIAU-derived radioactivity to areas of HSV1-tk gene expr

23 trated highly specific localization of [131I]FIAU-derived radioactivity to the area of ADV.RSV-tk-inj

24 i.v. administration of 1.6-2.8 mCi of [131I]FIAU.

25 transfected tissue can be imaged with [131I]FIAU and a gamma camera or SPECT, and that a significant

26 cells labeled in vitro or in vivo with [131I]FIAU or [124I]FIAU can be noninvasively tracked in SCID

27 agreement with these localization data, [14C]FIAU was efficiently transported into the mitochondria o

28 vers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in h

29 ethargy became progressively severe, and all FIAU-treated woodchucks died or were euthanized 78 to 11

30 h after the last vector administration, and FIAU positron emission tomography (PET) was performed 48

31 as observed between lacZ gene expression and FIAU accumulation 5-40 h after infection of 9L cells wit

32 ]-2'-fluoro-1-beta-D-arabinofuranosyluracil (FIAU) and imaged 24 h later with a gamma camera.

33 ondrial toxicity of nucleoside drugs such as FIAU.

34 SV-1-tk gene expression could be assessed by FIAU-PET after in vivo infection of s.c. tumors.

35 of DNA polymerase-gamma (DNA pol-gamma), by FIAU triphosphate (FIALTP) or by triphosphates of FIAU m

36 In stably expressing cells at 120 min, (14)C-FIAU uptake in RG2-TK tumor cells was 11.3 %ID (percenta

37 5-iodouracil-beta-d-arabinofuranoside ((14)C-FIAU) was also determined in RG2-TK rat glioma cells sta

38 Oligonucleotides containing FIAU at positions -1, 3 or 5, were much less able to com

39 al effect was equivocal, but at 1.5 mg/kg/d, FIAU had significant antiviral activity.

40 beta-d-arabinofuranosyl)-5-iodouracil ((18)F-FIAU) in normal dogs.

41 Using (124)I-FIAU, (18)F-FIAU, or (18)F-FEAU, it should be possible to image Delt

42 l dogs were intravenously administered (18)F-FIAU.

43 oxicity of the nucleoside drug, fialuridine (FIAU).

44 iviral activity and toxicity of fialuridine (FIAU; 1,-2'deoxy-2'fluoro-1-beta-D-arabinofuranosyl-5-io

45 ted with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure.

46 Many antiviral drugs (e.g. fialuridine; FIAU) produce clinically significant mitochondrial toxic

47 +/- 0.21 vs. 0.074 +/- 0.49 %dose/g) and for FIAU and FHPG (1.27 +/- 0.14 vs. 0.023 +/- 0.008 %dose/g

48 01, and 0.0077 +/- 0.0003 mL/min/g cells for FIAU, FHBG, and FHPG, respectively.

49 similar differences in RG2TK+ xenografts for FIAU and FHBG (1.22 +/- 0.21 vs. 0.074 +/- 0.49 %dose/g)

50 Plasma clearance was FHBG > FHPG >> FIAU.

51 Intratumoral distributions of (124)I-FIAU and (18)F-FMISO were similar, and eGFP, pimonidazol

52 Using (124)I-FIAU, (18)F-FIAU, or (18)F-FEAU, it should be possible t

53 iomarkers in the HT29-9HRE xenograft: (124)I-FIAU, (18)F-FMISO, Hoechst (perfusion), lectin-TRITC (fu

54 18)F-FMISO and the reporter substrate (124)I-FIAU, yielded similar tumor hypoxia images for the HT29-

55 We showed that PET, with [(124)I]FIAU (2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-[(1

56 colorectal tumor can be detected by [(124)I]FIAU PET imaging.

57 ta-D-5-iodouracil-arabinofuranoside ([(125)I]FIAU) to tumors engineered to express the Epstein-Barr v

58 of a therapeutic radiopharmaceutical [(131)I]FIAU to slow or stop tumor growth or to achieve tumor re

59 al abnormalities in the human hepatocytes in FIAU-treated chimeric mice.

60 gy, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treate

61 er characteristics all interact to influence FIAU accumulation and imaging.

62 luoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) was toxic in trials for chronic hepatitis B infect

63 1-beta-D-beta-arabinofuranosyl-5-iodouracil (FIAU), (18)F-2'-fluoro-2'-deoxy-1-beta-D-beta-arabinofur

64 eoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU), (18)F-labeled 9-[4-fluoro-3-(hydroxymethyl)butyl]

65 luoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU), beta-L-(-)-2',3'-dideoxy-3'-thiacytidine (-)3TC,

66 uoro-beta-D-arabino-furanosyl)-5-iodouracil (FIAU), is incorporated into DNA in cell culture and in v

67 fluoro-beta-D-arabinofuranosyl-5-iodouracil (FIAU), respectively.

68 eoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU).

69 uoro-beta-d-arabinofuranosyl)-5-iodouridine [FIAU]) and with acycloguanosine analogs using a stable H

70 nt of HSV-1-tk gene expression (124I-labeled FIAU % dose/g), 0.15 mCi of 124I-labeled FIAU was inject

71 led FIAU % dose/g), 0.15 mCi of 124I-labeled FIAU was injected i.v. 8 h after the last vector adminis

72 vity (TK expression measured as 131I-labeled FIAU % dose/g) and coexpressed lacZ gene activity.

73 Z gene coexpression, 0.2 mCi of 131I-labeled FIAU was injected i.v. 24 h after the last vector admini

74 Iodine 125 ((125)I)-labeled FIAU was used in vitro and iodine 131 ((131)I)-labeled F

75 sed in vitro and iodine 131 ((131)I)-labeled FIAU, in vivo.

76 cted cells in culture trapped (125)I-labeled FIAU and (99m)Tc-labeled P2045; uptake correlated with t

77 r (P <.05) than the uptake of (131)I-labeled FIAU at 1.6% +/- 0.4 dose per gram.

78 P <.05) than the 40% +/- 2 of (125)I-labeled FIAU that was trapped.

79 lated with Ad-hSSTr2-TK dose; (131)I-labeled FIAU tumor uptake did not correlate with vector dose.

80 -labeled P2045 and (125)I- or (131)I-labeled FIAU were imaged simultaneously with different window se

81 days, mtDNA decreased by 30% with 20 microM FIAU or 20 microM FMAU and decreased less than 10% with

82 Moreover, FIAU (50 microm) produced significant mitochondrial toxi

83 We also show the ability of FIAU-PET scanning to detect differences in viral infecti

84 red noninvasively by PET, where the areas of FIAU-derived radioactivity identify the viable portion o

85 nfected woodchucks were given 1.5 mg/kg/d of FIAU orally for 12 weeks, and the results compared with

86 city of infection, 1.5) led to a decrease of FIAU accumulation rates, viral yield, and cell pellet we

87 ) carrier woodchucks received daily doses of FIAU by intraperitoneal injection for 4 weeks.

88 Effects of FIAU, FMAU, and FAU on HepG2 cell mmtDNA abundance and u

89 These results indicate that incorporation of FIAU into DNA may induce local conformational changes re

90 o investigate the effect of incorporation of FIAU into DNA on the binding of transcription factors, o

91 The levels of FIAU accumulation were comparatively low (approximately

92 The levels of FIAU and FEAU accumulation in cells expressing DeltahTK2

93 roximately 10 min) selective localization of FIAU in RG2TK+ xenografts, whereas FHBG and FHPG are bei

94 The magnitude of FIAU accumulation in RG2TK+, W256TK+, and wild-type tumo

95 umors, which indicates that the magnitude of FIAU accumulation reflects the level of HSV1-tk gene exp

96 nvestigations of the molecular mechanisms of FIAU toxicity in vivo and for preclinical toxicological

97 nalyses determined biochemical mechanisms of FIAU, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) -5-me

98 al studies demonstrated that the presence of FIAU at a position 5' to the cleavage site in the consen

99 In contrast, the presence of FIAU, depending on its location, resulted in the increas

100 n ability, and that the accumulation rate of FIAU in culture, Ki, reflects the number of HSV-1 viral

101 The rates of FIAU accumulation (Ki) in hrR3-infected 9L cells in cult

102 aracteristic findings in the final stages of FIAU toxicity in woodchucks.

103 FIAU-treated chimeric mice mirrored those of FIAU-treated human participants.

104 atic difference in mitochondrial toxicity of FIAU between humans and rodents.

105 t that the lack of mitochondrial toxicity of FIAU in mice is due to the lack of mENT1 targeting to an

106 The mitochondrial toxicity of FIAU to Madin-Darby canine kidney cells was enhanced by

107 triphosphate (FIALTP) or by triphosphates of FIAU metabolites.

108 After 12 weeks of FIAU treatment, serum WHV DNA was not detectable by conv

109 ortion of infected tumor tissue that retains FIAU accumulation ability, and that the accumulation rat

110 control mice that were treated with the same FIAU doses for 14 d.

111 ied from 0.06 to 0.0004 s(-1) for the series FIAU > (+)3TC approximately equal to (-)3TC > CBV > AZT

112 ecific reporter substrate for DeltahTK2 than FIAU, whereas FHBG is not phosphorylated by this enzyme.

113 These results demonstrate that FIAU is resistant to metabolism and moderately incorpora

114 primates did not provide any indication that FIAU would be hepatotoxic in humans.

115 results (including the PET images) show that FIAU is a substantially more efficient probe than FHBG o

116 3 h) comparisons in RG2TK+ cells showed that FIAU accumulation was 15-fold greater than that of FHBG

117 al and cell biological findings suggest that FIAU and its metabolites inhibit mtDNA replication, most

118 The FIAU images showed significant stomach and some intestin

119 eeks, the serum WHV-DNA concentration in the FIAU-treated carrier group was two to three logs lower t

120 din-Darby canine kidney cells, can transport FIAU, confocal microscopy showed that mENT1-GFP (green f

121 isolated from mouse livers did not transport FIAU.

122 At 60 min after injection, unmetabolized FIAU radioactivity in blood and urine samples was greate

123 -2'-fluoro-1-beta-d-arabinofuranosyl-uracil (FIAU) could image cells infected with herpes simplex vir

124 oro-5-iodo-1-beta-D-arabinofuranosyl-uracil (FIAU), a selective substrate for viral thymidine kinase

125 oxy-1-beta-D-arabinofuranosyl-5-iodo-uracil (FIAU).

126 in-resistance) and negative selection (using FIAU to exclude cells lacking thymidine kinase), allowin

127 ormal tissues may need to be considered when FIAU is used to track reporter gene activity.

128 Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeri

129 th humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d.

130 e center of dyad symmetry) was replaced with FIAU, binding to AP-1 was abrogated.

131 the core binding sequence) was replaced with FIAU, binding to AP-1 was approximately 82, 28, 86 and 5

132 y was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d.

133 mean body weights of woodchucks treated with FIAU were significantly lower than controls.

134 t observed previously in humans treated with FIAU, suggesting that the woodchuck should be valuable i

135 After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinic