Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine

Kong, Xiangbin; Zhu, Qing-Yu; Vidal, Pedro; Watanabe, K. A.; Polsky, Bruce; Armstrong, Donald; Ostrander, Michael; Lang, Stanley A.; Muchmore, Elizabeth; Chou, Ting‐Chao

doi:10.1128/aac.36.4.808

Cited by 135 publications

(72 citation statements)

References 37 publications

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“…Before this study, only hENT1 was known to transport FLT across plasma membranes, and whether the other hNTs could transport FLT was unknown (Kong et al, 1992). The current study has determined that FLT can interact with and is transported by hENT1, hENT2, hCNT1, and hCNT3.…”

Section: Discussionmentioning

confidence: 98%

“…Increased FLT accumulation in proliferating cells is believed to be due to a proliferation-dependent increase in thymidine kinase 1 (TK1) activity, leading to increased intracellular phosphorylation and "trapping" of FLT (Rasey et al, 2002;Grierson et al, 2004;Barthel et al, 2005). However, FLT must cross plasma membranes before it can interact with TK1, and human nucleoside transporters (hNTs) are thought to be involved in this process because FLT uptake in HL-60 cells was significantly reduced by inhibiting human equilibrative nucleoside transporter 1 (hENT1) (Kong et al, 1992).…”

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confidence: 99%

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The Role of Human Nucleoside Transporters in Uptake of 3′-Deoxy-3′-fluorothymidine

Paproski¹,

Ng²,

Yao³

et al. 2008

Mol Pharmacol

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

The Role of Human Nucleoside Transporters in Uptake of 3′-Deoxy-3′-fluorothymidine

Paproski¹,

Ng²,

Yao³

et al. 2008

Mol Pharmacol

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“…Although ZDV is only one of an increasing number of similarly acting nucleoside reverse transcriptase inhibitors, it is still the first-line therapy for HIV sufferers worldwide [4][5][6]. ZDV and other 2',3'-dideoxynucleosides are inactive against the target viral reverse transcriptase enzyme, requiring intracellular phosphorylation to their putative active triphosphate forms [7][8][9][10][11][12][13]. ZDV enters target lymphocytes by passive diffusion [14] and is converted via ZDV monophosphate and ZDV diphosphate to the active triphosphate metabolite (ZDV triphosphate), the intracellular enzymes involved being thymidine kinase, thymidylate kinase and pyrimidine nucleoside diphosphate kinase respectively [7].…”

Section: Introductionmentioning

confidence: 99%

Effects of dideoxyinosine and dideoxycytidine on the intracellular phosphorylation of zidovudine in human mononuclear cells.

Veal

Wild

Barry

et al. 1994

Brit J Clinical Pharma

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“…The low sensitivity of 18 F-FLT for detection of viable residual tumor in our study may be related to the lower tissue uptake of 18 F-FLT than of 18 F-FDG in GCTs-a finding that has also been reported for several other tumors (17,19,21,29,35). It may be explained by a competition between 18 F-FLT and endogenous thymidine for uptake transporter and phosphorylation by thymidine kinase 1 (36). Moreover, there are data demonstrating that 18 F-FLT uptake and transport are determined not by thymidine kinase 1 activity alone but also by adenosine triphosphate levels (37,38).…”

Section: Discussionmentioning

confidence: 33%

PET/CT with ¹⁸F-FLT: Does It Improve the Therapeutic Management of Metastatic Germ Cell Tumors?

Pfannenberg

Aschoff²,

Dittmann³

et al. 2010

J Nucl Med

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Because 18 F-FDG PET alone has only limited value in metastatic germ cell tumors (GCTs), we investigated the addition of 39-deoxy-39-18 F-fluorothymidine (FLT) to 18 F-FDG for early response monitoring and prediction of the histology of residual tumor masses in patients with metastatic GCT. Methods: Eleven patients with metastatic GCT were examined with both 18 F-FDG PET/CT and 18 F-FLT PET/CT before chemotherapy, after the first cycle of chemotherapy (early response), and 3 wk after completion of chemotherapy. In 1 patient with negative 18 F-FLT PET/CT results before chemotherapy, no further 18 F-FLT scanning was performed. PET images were analyzed visually and, using standardized uptake values (SUVs), semiquantitatively. The results were compared with the findings of CT and tumor marker levels and validated by histopathologic examination of resected residual masses, including Ki-67 immunostaining (7 patients), or by clinicoradiologic follow-up for at least 6 mo (4 patients). A responder was defined as a patient showing the presence of necrosis, a complete remission, or a marker-negative partial remission within a minimum progression-free interval of 6 mo. Early treatment response was judged according to the criteria of the European Organization for Research and Treatment of Cancer. Results: Before chemotherapy, reference lesions showed increased 18 F-FDG uptake (mean SUV, 8.8; range, 2.9-15.0) in all patients and moderate 18 F-FLT uptake (mean SUV, 3.7; range, 1.7-9.7) in 10 of 11 patients. After 1 cycle of chemotherapy, mean SUV decreased in responders and nonresponders by 64% and 60%, respectively, for 18 F-FDG (P 5 0.8) and by 58% and 48%, respectively, for 18 F-FLT (P 5 0.5). After the end of chemotherapy, mean SUV decreased in responders and nonresponders by 85% and 73%, respectively, for 18 F-FDG (P 5 0.1) and by 68% and 65%, respectively, for 18 F-FLT (P 5 0.8). The results of early and final PET were inconsistent in 6 of 11 patients for 18 F-FDG and in 4 of 10 patients for 18 F-FLT. Both patients with teratoma had false-negative results on both 18 F-FDG and 18 F-FLT. The sensitivity, specificity, positive predictive value, and negative predictive value for detection of viable tumor after 1 cycle of chemotherapy were 60%, 33%, 43%, and 50%, respectively, for 18 F-FDG and 60%, 80%, 75%, and 67%, respectively, for 18 F-FLT PET/CT. The respective values after the end of chemotherapy were 20%, 100%, 100%, and 60% for 18 F-FDG and 0%, 100%, 0%, and 50% for 18 F-FLT PET/CT. Conclusion: PET-negative residual masses after chemotherapy of metastatic GCT still require resection, since the low negative predictive value of 18 F-FDG PET for viable tumor cannot be improved by application of 18 F-FLT.

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Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine

Cited by 135 publications

References 37 publications

The Role of Human Nucleoside Transporters in Uptake of 3′-Deoxy-3′-fluorothymidine

The Role of Human Nucleoside Transporters in Uptake of 3′-Deoxy-3′-fluorothymidine

Effects of dideoxyinosine and dideoxycytidine on the intracellular phosphorylation of zidovudine in human mononuclear cells.

PET/CT with ¹⁸F-FLT: Does It Improve the Therapeutic Management of Metastatic Germ Cell Tumors?

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Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine

Cited by 135 publications

References 37 publications

The Role of Human Nucleoside Transporters in Uptake of 3′-Deoxy-3′-fluorothymidine

The Role of Human Nucleoside Transporters in Uptake of 3′-Deoxy-3′-fluorothymidine

Effects of dideoxyinosine and dideoxycytidine on the intracellular phosphorylation of zidovudine in human mononuclear cells.

PET/CT with 18F-FLT: Does It Improve the Therapeutic Management of Metastatic Germ Cell Tumors?

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PET/CT with ¹⁸F-FLT: Does It Improve the Therapeutic Management of Metastatic Germ Cell Tumors?