Genomes and Genes
Summary: Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'-triphosphates and act as chain-terminating inhibitors of viral reverse transcription.
- Wang H, Zhang J, Tian J, Qu B, Li T, Chen Y, et al. Using dual-tracer PET to predict the biologic behavior of human colorectal cancer. J Nucl Med. 2009;50:1857-64 pubmed publisher..182). High uptake of (18)F-FDG and (18)F-FLT may reflect poorer survival and a higher metastatic potential for CRC in mice. Combining (18)F-FDG with (18)F-FLT PET would be helpful in better predicting the biologic behavior of CRC. ..
- Choi A, Vittinghoff E, Deeks S, Weekley C, Li Y, Shlipak M. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons. AIDS. 2011;25:1289-98 pubmed publisher..16). Recent abacavir exposure was independently associated with increased risk for cardiovascular events. We also observed an association between recent tenofovir exposure and heart failure, which needs to be confirmed in future studies. ..
- Bedimo R, Westfall A, Drechsler H, Vidiella G, Tebas P. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis. 2011;53:84-91 pubmed publisher..Abacavir use was more common than was tenofovir use among patients with prior chronic kidney disease, and chronic kidney disease independently predicted higher rates of AMI and CVA. ..
- Debucquoy A, Devos E, Vermaelen P, Landuyt W, De Weer S, Van den Heuvel F, et al. 18F-FLT and 18F-FDG PET to measure response to radiotherapy combined with celecoxib in two colorectal xenograft models. Int J Radiat Biol. 2009;85:763-71 pubmed publisher..The contradicting in vitro and in vivo results suggest a major role of the tumour micro-environment. (18)F-FLT seems a good alternative for (18)F-FDG to follow tumour growth after radiation treatment. ..
- Sluis Cremer N, Koontz D, Bassit L, Hernandez Santiago B, Detorio M, Rapp K, et al. Anti-human immunodeficiency virus activity, cross-resistance, cytotoxicity, and intracellular pharmacology of the 3'-azido-2',3'-dideoxypurine nucleosides. Antimicrob Agents Chemother. 2009;53:3715-9 pubmed publisher..The present data suggest that additional preclinical studies are warranted to assess the potential of ADPNs for treatment of HIV-1 infection. ..
- McComsey G, Kitch D, Daar E, Tierney C, Jahed N, Tebas P, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of. J Infect Dis. 2011;203:1791-801 pubmed publisher..Compared with ABC-3TC, TDF-FTC-treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898. ..
- Zander T, Scheffler M, Nogova L, Kobe C, Engel Riedel W, Hellmich M, et al. Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F]fluorodeoxyglucose and [(18)F]fluorothymidine positron emission tomography. J Clin Oncol. 2011;29:1701-8 pubmed publisher..Early FDG-PET predicts PFS, OS, and nonprogression after 6 weeks of therapy with erlotinib in unselected, previously untreated patients with advanced NSCLC independent from EGFR mutational status. ..
- Zhang C, Yan Z, Li W, Kuszpit K, Painter C, Zhang Q, et al. [(18)F]FLT-PET imaging does not always "light up" proliferating tumor cells. Clin Cancer Res. 2012;18:1303-12 pubmed publisher..With careful validation, [(18)F]FLT-PET imaging can be used to monitor antiproliferative therapies in tracer-avid malignancies. ..
- Frings V, de Langen A, Smit E, van Velden F, Hoekstra O, Van Tinteren H, et al. Repeatability of metabolically active volume measurements with 18F-FDG and 18F-FLT PET in non-small cell lung cancer. J Nucl Med. 2010;51:1870-7 pubmed publisher..Considering the balance between the success rate of automatic tumor delineation and repeatability of metabolic volume, a 50% threshold with correction for local background activity (A50%) seems optimal among the VOI methods evaluated. ..
- Cruciani M, Zanichelli V, Serpelloni G, Bosco O, Malena M, Mazzi R, et al. Abacavir use and cardiovascular disease events: a meta-analysis of published and unpublished data. AIDS. 2011;25:1993-2004 pubmed publisher..82, 95% CI 0.67-1.00; P = 0.05). This meta-analysis of RCTs does not support the hypothesis that ABC-containing cART regimens carry a greater risk of MI or major cardiovascular events relative to comparator cART. ..
- Hileman C, Wohl D, Tisch D, Debanne S, McComsey G. Short communication: initiation of an abacavir-containing regimen in HIV-infected adults is associated with a smaller decrease in inflammation and endothelial activation markers compared to non-abacavir-containing regimens. AIDS Res Hum Retroviruses. 2012;28:1561-4 pubmed publisher..When taken with an NNRTI, abacavir induced a smaller decrease in inflammation biomarkers in this cohort, suggesting a possible proinflammatory effect of this nucleoside analogue. ..
- Baum P, Sullam P, Stoddart C, McCune J. Abacavir increases platelet reactivity via competitive inhibition of soluble guanylyl cyclase. AIDS. 2011;25:2243-8 pubmed publisher..Abacavir competitively inhibits guanylyl cyclase, leading to platelet hyperreactivity. This may explain the observed increased risk of myocardial infarction in HIV patients taking abacavir. ..
- Weber M, Henze M, Tüttenberg J, Stieltjes B, Meissner M, Zimmer F, et al. Biopsy targeting gliomas: do functional imaging techniques identify similar target areas?. Invest Radiol. 2010;45:755-68 pubmed publisher..Both imaging techniques that depict microcirculation and techniques that visualize proliferation identify similar target areas. ..
- Perumal M, Stronach E, Gabra H, Aboagye E. Evaluation of 2-deoxy-2-[18F]fluoro-D-glucose- and 3'-deoxy-3'-[18F]fluorothymidine-positron emission tomography as biomarkers of therapy response in platinum-resistant ovarian cancer. Mol Imaging Biol. 2012;14:753-61 pubmed publisher..Therapeutic inhibition of AKT activation in acquired platinum-resistant disease can be imaged noninvasively by [(18)F]FDG-PET and [(18)F]FLT-PET warranting further assessment. ..
- Rasmussen T, Tolstrup M, Melchjorsen J, Frederiksen C, Nielsen U, Langdahl B, et al. Evaluation of cardiovascular biomarkers in HIV-infected patients switching to abacavir or tenofovir based therapy. BMC Infect Dis. 2011;11:267 pubmed publisher..The clinical significance of these findings is uncertain. TRIAL REGESTRATION: Clinicaltrials.gov identifier: NCT00647244. ..
- Palella F, Gange S, Benning L, Jacobson L, Kaplan R, Landay A, et al. Inflammatory biomarkers and abacavir use in the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. AIDS. 2010;24:1657-65 pubmed publisher..To assess associations between abacavir (ABC) use and systemic inflammation...
- Falcinelli E, Francisci D, Belfiori B, Petito E, Guglielmini G, Malincarne L, et al. In vivo platelet activation and platelet hyperreactivity in abacavir-treated HIV-infected patients. Thromb Haemost. 2013;110:349-57 pubmed publisher..In conclusion, treatment with ABC enhances in vivo platelet activation and induces platelet hyperreactivity by blunting the inhibitory effects of NO on platelets. These effects may lead to an increase of ischaemic cardiovascular events. ..
- Obel N, Farkas D, Kronborg G, Larsen C, Pedersen G, Riis A, et al. Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study. HIV Med. 2010;11:130-6 pubmed publisher..We confirmed the association between abacavir use and increased risk of MI. Further studies are needed to control for potential confounding not measured in research to date. ..
- Yamamoto Y, Ono Y, Aga F, Kawai N, Kudomi N, Nishiyama Y. Correlation of 18F-FLT uptake with tumor grade and Ki-67 immunohistochemistry in patients with newly diagnosed and recurrent gliomas. J Nucl Med. 2012;53:1911-5 pubmed publisher..18)F-FLT PET seems to be useful in the noninvasive assessment of grade and proliferation in gliomas, especially newly diagnosed gliomas. ..
- Idema A, Hoffmann A, Boogaarts H, Troost E, Wesseling P, Heerschap A, et al. 3'-Deoxy-3'-18F-fluorothymidine PET-derived proliferative volume predicts overall survival in high-grade glioma patients. J Nucl Med. 2012;53:1904-10 pubmed publisher..024, log rank) for this threshold. The PV as determined by (18)F-FLT PET is associated with OS in high-grade malignant gliomas. The SBR method yielded the best results to predict short and long OS. ..
- Martin J, Hitchcock M, De Clercq E, Prusoff W. Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: a brief history of stavudine (D4T) and its comparison with other dideoxynucleosides. Antiviral Res. 2010;85:34-8 pubmed publisher..It has only recently been supplanted by better-tolerated treatments. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. ..
- Enslow M, Zollinger L, Morton K, Butterfield R, Kadrmas D, Christian P, et al. Comparison of 18F-fluorodeoxyglucose and 18F-fluorothymidine PET in differentiating radiation necrosis from recurrent glioma. Clin Nucl Med. 2012;37:854-61 pubmed publisher..The objective was to compare F-fluorodeoxyglucose (FDG) and F-fluorothymidine (FLT) PET in differentiating radiation necrosis from recurrent glioma...
- Li Z, Graf N, Herrmann K, Junger A, Aichler M, Feuchtinger A, et al. FLT-PET is superior to FDG-PET for very early response prediction in NPM-ALK-positive lymphoma treated with targeted therapy. Cancer Res. 2012;72:5014-24 pubmed publisher..In conclusion, we show that FLT-PET but not FDG-PET is able to predict response to treatment with specific inhibitors very early in the course of treatment and thus enables early prediction of treatment efficacy. ..
- Post F, Moyle G, Stellbrink H, Domingo P, Podzamczer D, Fisher M, et al. Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr. 2010;55:49-57 pubmed publisher..A significant difference in efficacy favoring tenofovir/emtricitabine was observed. ..
- McComsey G, Kitch D, Daar E, Tierney C, Jahed N, Melbourne K, et al. Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir. AIDS. 2012;26:1371-85 pubmed publisher..89). Soluble TNF-receptors and adhesion molecules decreased following treatment initiation and did not differ by regimens. Differences were seen on hsCRP and IL-6 changes with ABC/3TC vs. TDF/FTC and on hsCRP with EFV vs. ATV/r. ..
- Scheffler M, Kobe C, Zander T, Nogova L, Kahraman D, Thomas R, et al. Monitoring reversible and irreversible EGFR inhibition with erlotinib and afatinib in a patient with EGFR-mutated non-small cell lung cancer (NSCLC) using sequential [18F]fluorothymidine (FLT-)PET. Lung Cancer. 2012;77:617-20 pubmed publisher..Our observations confirm the value of molecular imaging for assessment of pharmacodynamics and early prediction of response and relapse in these patients. ..
- Chalkidou A, Landau D, Odell E, Cornelius V, O Doherty M, Marsden P. Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in patients with cancer: A systematic review and meta-analysis. Eur J Cancer. 2012;48:3499-513 pubmed publisher..Sufficient data to support a strong correlation for brain, lung and breast cancer exist. However, larger, prospective studies with improved study design are warranted to validate these findings for the rest of the cancer types. ..
- SOLOVIEV D, Lewis D, Honess D, Aboagye E. [(18)F]FLT: an imaging biomarker of tumour proliferation for assessment of tumour response to treatment. Eur J Cancer. 2012;48:416-24 pubmed publisher..Nevertheless FLT-PET could potentially be used as a negative predictor of tumour response to chemotherapy, and hence evaluation of this IB is granted in multi-centre clinical trials. ..
- Schwarzenberg J, Czernin J, Cloughesy T, Ellingson B, Pope W, Geist C, et al. 3'-deoxy-3'-18F-fluorothymidine PET and MRI for early survival predictions in patients with recurrent malignant glioma treated with bevacizumab. J Nucl Med. 2012;53:29-36 pubmed publisher..18)F-FLT PET seems to be more predictive than MRI for early treatment response. ..
- Aarntzen E, Srinivas M, de Wilt J, Jacobs J, Lesterhuis W, Windhorst A, et al. Early identification of antigen-specific immune responses in vivo by [18F]-labeled 3'-fluoro-3'-deoxy-thymidine ([18F]FLT) PET imaging. Proc Natl Acad Sci U S A. 2011;108:18396-9 pubmed publisher..This technique allows for early discrimination of responding from nonresponding patients in anti-cancer vaccination and aid physicians in individualized decisionmaking. ..
- de Pablo C, Orden S, Peris J, Barrachina M, Esplugues J, Alvarez A. Profile of leukocyte-endothelial cell interactions induced in venules and arterioles by nucleoside reverse-transcriptase inhibitors in vivo. J Infect Dis. 2013;208:1448-53 pubmed publisher..There is controversy regarding cardiovascular (CV) toxicity of the nucleoside reverse-transcriptase inhibitors used to treat human immunodeficiency virus infection...
- Satchell C, O Halloran J, Cotter A, Peace A, O Connor E, Tedesco A, et al. Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy. J Infect Dis. 2011;204:1202-10 pubmed publisher..025). The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients. ..
- Wardak M, Schiepers C, Dahlbom M, Cloughesy T, Chen W, Satyamurthy N, et al. Discriminant analysis of ¹?F-fluorothymidine kinetic parameters to predict survival in patients with recurrent high-grade glioma. Clin Cancer Res. 2011;17:6553-62 pubmed publisher..Discriminant analysis using changes in ¹?F-FLT kinetic parameters early during treatment seems to be a powerful method for evaluating the efficacy of therapeutic regimens. ..
- Moroz M, Kochetkov T, Cai S, Wu J, Shamis M, Nair J, et al. Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [18F]fluoro-2-deoxyglucose and 3'-deoxy-3'-[18F]fluorothymidine imaging. Clin Cancer Res. 2011;17:1099-110 pubmed publisher..These observations suggest that de novo thymidine synthesis could be a limitation and confounding factor for [(18)F]FLT PET imaging and quantification of tumor proliferation, and this may apply to some clinical studies as well. ..
- Jensen M, Erichsen K, Bjorkling F, Madsen J, Jensen P, Højgaard L, et al. Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice. PLoS ONE. 2010;5:e12965 pubmed publisher..Our data indicate that (18)F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients. ..
- Aide N, Kinross K, Cullinane C, Roselt P, Waldeck K, Neels O, et al. 18F-FLT PET as a surrogate marker of drug efficacy during mTOR inhibition by everolimus in a preclinical cisplatin-resistant ovarian tumor model. J Nucl Med. 2010;51:1559-64 pubmed publisher..These data suggest that early treatment monitoring by (18)F-FLT PET may be of use in future preclinical or clinical trials evaluating treatment of cisplatin-resistant ovarian tumors by mTOR inhibitors. ..
- Lee S, Kim S, Chung J, Oh S, Ryu J, Hong Y, et al. Induction of thymidine kinase 1 after 5-fluorouracil as a mechanism for 3'-deoxy-3'-[18F]fluorothymidine flare. Biochem Pharmacol. 2010;80:1528-36 pubmed publisher..05). Conclusively, 5-FU induced TK1 and TK1-mediated high [(18)F]FLT flare in most of cell lines. [(18)F]FLT-PET may be used to assess pharmacodynamics of TS inhibitor by a mechanism involving TK1 induction. ..
- Yamamoto Y, Kameyama R, Izuishi K, Takebayashi R, Hagiike M, Asakura M, et al. Detection of colorectal cancer using ¹?F-FLT PET: comparison with ¹?F-FDG PET. Nucl Med Commun. 2009;30:841-5 pubmed publisher..Neither of the two radiotracers used was correlated with proliferative activity. ..
- Sax P, Tierney C, Collier A, Fischl M, Mollan K, Peeples L, et al. Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med. 2009;361:2230-40 pubmed publisher..ClinicalTrials.gov number, NCT00118898.) ..
- Zhang H, Coats S, Bondada L, Amblard F, Detorio M, Asif G, et al. Synthesis and evaluation of 3'-azido-2',3'-dideoxypurine nucleosides as inhibitors of human immunodeficiency virus. Bioorg Med Chem Lett. 2010;20:60-4 pubmed publisher..Among the synthesized compounds, several show potent and selective anti-HIV activity in primary lymphocytes. ..
- Shah C, Miller T, Wyatt S, McKinley E, Olivares M, Sanchez V, et al. Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical models of breast cancer. Clin Cancer Res. 2009;15:4712-21 pubmed publisher..Although promising in one preclinical model, further studies are required to determine the overall value of [18F]FLT-PET as a biomarker of response to trastuzumab in HER2+ breast cancer. ..
- Nageswara Rao R, Shinde D. Two-dimensional LC-MS/MS determination of antiretroviral drugs in rat serum and urine. J Pharm Biomed Anal. 2009;50:994-9 pubmed publisher..7 ng ml(-1). The calibration graphs were linear in the range of 4-50 ng ml(-1)for abacavir, nevirapine and indinavir. The method was successfully applied to study the pharmacokinetics of antiretroviral in rats. ..
- Martin A, Bloch M, Amin J, Baker D, Cooper D, Emery S, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-Lamivudine: a randomized, 96-week trial. Clin Infect Dis. 2009;49:1591-601 pubmed publisher..In this population, TDF-FTC and ABC-3TC had similar virological efficacy, but ABC-3TC was associated with more serious non-AIDS events, particularly cardiovascular events. Clinical trials registration. NCT00192634 . ..
- Ding X, Andraca Carrera E, Cooper C, Miele P, Kornegay C, Soukup M, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. J Acquir Immune Defic Syndr. 2012;61:441-7 pubmed publisher..26% to 0.27%). To the best of our knowledge, our study represents the largest trial-level meta-analysis to date of clinical trials in which ABC use was randomized. Our analysis found no association between ABC use and MI risk. ..
- Schiepers C, Dahlbom M, Chen W, Cloughesy T, Czernin J, Phelps M, et al. Kinetics of 3'-deoxy-3'-18F-fluorothymidine during treatment monitoring of recurrent high-grade glioma. J Nucl Med. 2010;51:720-7 pubmed publisher..The correlation coefficient between SUV(late) and influx rate was 0.91, permitting response monitoring by the measurement of (18)F-FLT uptake changes. ..
- Lang S, Mary Krause M, Cotte L, Gilquin J, Partisani M, Simon A, et al. Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med. 2010;170:1228-38 pubmed publisher
- Stellbrink H, Orkin C, Arribas J, Compston J, Gerstoft J, Van Wijngaerden E, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis. 2010;51:963-72 pubmed publisher..Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine. ..