Gemcitabine mechanism of action confounds early assessment of treatment response by 3′-Deoxy-3′-[18F]fluorothymidine in preclinical models of lung cancer

Cancer Research

Volumn 76, Issue 24, 2016, Pages 7096-7105

  Schelhaas, Sonja ^a   Held, Annelena ^a,e   Wachsmuth, Lydia ^b   Hermann, Sven ^a   Honess, Davina J ^c   Heinzmann, Kathrin ^c,f   Smith, Donna Michelle ^c   Griffiths, John R ^c   Faber, Cornelius ^b   Jacobs, Andreas H ^a,d  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d Johanniter Krankenhaus   (Germany)

^e OTTO VON GUERICKE UNIVERSITY   (Germany)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3' FLUOROTHYMIDINE F 18; GEMCITABINE; KI 67 ANTIGEN; THYMIDINE KINASE; THYMIDYLATE SYNTHASE; TRACER; 2',3' DIDEOXYNUCLEOSIDE DERIVATIVE; 3' FLUOROTHYMIDINE; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; RADIOPHARMACEUTICAL AGENT;

A-549 CELL LINE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CANCER MODEL; CELL DEATH; CONTROLLED STUDY; DIFFUSION WEIGHTED IMAGING; DRUG EXCRETION; DRUG MECHANISM; DRUG RESPONSE; DRUG UPTAKE; HUMAN; HUMAN CELL; LUNG CANCER; MOUSE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REPEATED DRUG DOSE; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; DIAGNOSTIC IMAGING; DISEASE MODEL; DRUG SCREENING; FEMALE; FLOW CYTOMETRY; IMAGE PROCESSING; IMMUNOHISTOCHEMISTRY; LUNG TUMOR; NUDE MOUSE; PROCEDURES; TUMOR CELL LINE; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC AGENTS; BLOTTING, WESTERN; CELL LINE, TUMOR; DEOXYCYTIDINE; DIDEOXYNUCLEOSIDES; DIFFUSION MAGNETIC RESONANCE IMAGING; DISEASE MODELS, ANIMAL; FEMALE; FLOW CYTOMETRY; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; IMMUNOHISTOCHEMISTRY; LUNG NEOPLASMS; MICE; MICE, NUDE; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85006925432     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-16-1479     Document Type: Article

References (35)

1. Been LB, Suurmeijer AJH, Cobben DCP, Jager PL, Hoekstra HJ, Elsinga PH. [18F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging 2004;31:1659-72.
2. Chalkidou A, Landau DB, Odell EW, Cornelius VR, O'Doherty MJ, Marsden PK. 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.
3. 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.
4. Sinkus R, Van Beers BE, Vilgrain V, DeSouza N, Waterton JC. Apparent diffusion coefficient from magnetic resonance imaging as a biomarker in oncology drug development. Eur J Cancer 2012;48:425-31.
5. Le Bihan D, Iima M. Diffusion magnetic resonance imaging: what water tells us about biological tissues. PLoS Biol 2015;13:e1002203.
6. Reynolds JK, Levien TL. Quality-of-life assessment in phase III clinical trials of gemcitabine in non-small-cell lung cancer. Drugs Aging 2008;25:893-911.
7. de Sousa Cavalcante L, Monteiro G. Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol 2014;741:8-16.
8. Honeywell RJ, Ruiz van Haperen VWT, Veerman G, Smid K, Peters GJ. Inhibition of thymidylate synthase by 2′,2′-difluoro-2′-deoxycytidine (Gemcitabine) and its metabolite 2′,2′-difluoro-2′-deoxyuridine. Int J Biochem Cell Biol 2015;60:73-81.
9. Mini E, Nobili S, Caciagli B, Landini I, Mazzei T. Cellular pharmacology of gemcitabine. Ann Oncol 2006;17:v7-12.
10. Lee SJ, Kim SY, Chung JH, Oh SJ, Ryu JS, Hong YS, 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.
11. Hong IK, Kim SY, Chung JH, Lee SJ, Oh SJ, Lee SJ, et al. 3′-Deoxy-3′-[18F]fluorothymidine positron emission tomography imaging of thymidine kinase 1 activity after 5-fluorouracil treatment in a mouse tumor model. Anticancer Res 2014;34:759-66.
12. Viel T, Schelhaas S, Wagner S, Wachsmuth L, Schwegmann K, Kuhlmann M, et al. Early assessment of the efficacy of temozolomide chemotherapy in experimental glioblastoma using [18F]FLT-PET imaging. PLoS One 2013;8:e67911.
13. Schäfers KP, Reader AJ, Kriens M, Knoess C, Schober O, Schäfers M. Performance evaluation of the 32-module quadHIDAC small-animal PET scanner. J Nucl Med 2005;46:996-1004.
14. Heinzmann K, Honess DJ, Lewis DY, Smith D-M, Cawthorne C, Keen H, et al. The relationship between endogenous thymidine concentrations and [(18)F]FLT uptake in a range of preclinical tumour models. EJNMMI Res 2016;6:63.
15. Bapiro TE, Richards FM, Goldgraben MA, Olive KP, Madhu B, Frese KK, et al. A novel method for quantification of gemcitabine and its metabolites 2′,2′-difluorodeoxyuridine and gemcitabine triphosphate in tumour tissue by LC-MS/MS: comparison with (19)F NMR spectroscopy. Cancer Chemother Pharmacol 2011;68:1243-53.
16. Schelhaas S, Wachsmuth L, Viel T, Honess DJ, Heinzmann K, Smith D-M, et al. Variability of proliferation and diffusion in different lung cancer models as measured by 3′-deoxy-3′-18F-fluorothymidine PET and diffusion-weighted MR imaging. J Nucl Med 2014;55:983-8.
17. Veerman G, Ruiz van Haperen VW, Vermorken JB, Noordhuis P, Braakhuis BJ, Pinedo HM, et al. Antitumor activity of prolonged as compared with bolus administration of 2′,2′-difluorodeoxycytidine invivo against murine colon tumors. Cancer Chemother Pharmacol 1996;38:335-42.
18. Wang H, Li M, Rinehart JJ, Zhang R. Pretreatment with dexamethasone increases antitumor activity of carboplatin and gemcitabine in mice bearing human cancer xenografts: in vivo activity, pharmacokinetics, and clinical implications for cancer chemotherapy. Clin Cancer Res 2004;10:1633-44.
19. Jensen MM, Kjaer A. Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET: a comprehensive review of pre-clinical studies. Am J Nucl Med Mol Imaging 2015;5:431-56.
20. Schelhaas S, Heinzmann K, Bollineni VR, Kramer GM, Liu Y, Waterton JC, et al. Preclinical applications of 3′-deoxy-3′-[18F]fluorothymidine in oncology - a systematic review. Theranostics 2017;7:40-50.
21. Perumal M, Pillai RG, Barthel H, Leyton J, Latigo JR, Forster M, et al. Redistribution of nucleoside transporters to the cell membrane provides a novel approach for imaging thymidylate synthase inhibition by positron emission tomography. Cancer Res 2006;66:8558-64.
22. Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early changes in [18F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med Mol Imaging 2002;29:1462-9.
23. Santini D, Schiavon G, Vincenzi B, Cass CE, Vasile E, Manazza AD, et al. Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC). Curr Cancer Drug Targets 2011;11:123-9.
24. Borbath I, Verbrugghe L, Lai R, Gigot JF, Humblet Y, Piessevaux H, et al. Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma. Eur J Cancer 2012;48:990-6.
25. Greenhalf W, Ghaneh P, Neoptolemos JP, Palmer DH, Cox TF, Lamb RF, et al. Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. J Natl Cancer Inst 2014;106:djt347.
26. Paproski RJ, Young JD, Cass CE. Predicting gemcitabine transport and toxicity in human pancreatic cancer cell lines with the positron emission tomography tracer 3′-deoxy-3′-fluorothymidine. Biochem Pharmacol 2010;79:587-95.
27. Awasthi N, Zhang C, Schwarz AM, Hinz S, Wang C, Williams NS, et al. Comparative benefits of Nab-paclitaxel over gemcitabine or polysorbate-based docetaxel in experimental pancreatic cancer. Carcinogenesis 2013;34:2361-9.
28. Zhang CC, Yan Z, Li W, Kuszpit K, Painter CL, Zhang Q, et al. [(18)F]FLT-PET imaging does not always "light up" proliferating tumor cells. Clin Cancer Res 2012;18:1303-12.
29. Clarke SJ, Farrugia DC, Aherne GW, Pritchard DM, Benstead J, Jackman AL. Balb/c mice as a preclinical model for raltitrexed-induced gastrointestinal toxicity. Clin Cancer Res 2000;6:285-96.
30. Li KM, Rivory LP, Hoskins J, Sharma R, Clarke SJ. Altered deoxyuridine and thymidine in plasma following capecitabine treatment in colorectal cancer patients. Br J Clin Pharmacol 2007;63:67-74.
31. Kim I-Y, Kang Y-S, Lee DS, Park H-J, Choi E-K, Oh Y-K, et al. Antitumor activity of EGFR targeted pH-sensitive immunoliposomes encapsulating gemcitabine in A549 xenograft nude mice. J Control Release 2009;140:55-60.
32. Zundelevich A, Elad-Sfadia G, Haklai R, Kloog Y. Suppression of lung cancer tumor growth in a nude mouse model by the Ras inhibitor salirasib (farnesylthiosalicylic acid). Mol Cancer Ther 2007;6:1765-73.
33. Yau K, Price P, Pillai RG, Aboagye E. Elevation of radiolabelled thymidine uptake in RIF-1 fibrosarcoma and HT29 colon adenocarcinoma cells after treatment with thymidylate synthase inhibitors. Eur J Nucl Med Mol Imaging 2006;33:981-7.
34. Viertl D, Bischof Delaloye A, Lanz B, Poitry-Yamate C, Gruetter R, Mlynarik V, et al. Increase of [(18)F]FLT tumor uptake invivo mediated by FdUrd: toward improving cell proliferation positron emission tomography. Mol Imaging Biol 2011;13:321-31.
35. Reichardt W, Juettner E, Uhl M, Elverfeldt DV, Kontny U. Diffusion-weighted imaging as predictor of therapy response in an animal model of Ewing sarcoma. Invest Radiol 2009;44:298-303.