[18F]-FLT positron emission tomography can be used to image the response of sensitive tumors to PI3-Kinase inhibition with the novel agent GDC-0941

Molecular Cancer Therapeutics

Volumn 12, Issue 5, 2013, Pages 819-828

  Cawthorne, Christopher ^a,e   Burrows, Natalie ^b   Gieling, Roben G ^b   Morrow, Christopher J ^c   Forster, Duncan ^a   Gregory, Jamil ^a   Radigois, Marc ^a   Smigova, Alison ^a   Babur, Muhammad ^a,b   Simpson, Kathryn ^c   Hodgkinson, Cassandra ^c   Brown, Gavin ^a   McMahon, Adam ^a   Dive, Caroline ^c   Hiscock, Duncan ^d   Wilson, Ian ^d   Williams, Kaye J ^a,b  

^a UNIVERSITY OF MANCHESTER   (United Kingdom)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

^d GE HEALTHCARE   (United Kingdom)

^e UNIVERSITY OF HULL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3' FLUOROTHYMIDINE F 18; PHOSPHATIDYLINOSITOL 3 KINASE; PICTILISIB; PROTEIN P85; THYMIDINE KINASE; 2',3' DIDEOXYNUCLEOSIDE DERIVATIVE; 2-(1H-INDAZOL-4-YL)-6-(4-METHANESULFONYLPIPERAZIN-1-YLMETHYL)-4-MORPHOLIN-4-YLTHIENO(3,2-D)PYRIMIDINE; 3' FLUOROTHYMIDINE; ANTINEOPLASTIC AGENT; INDAZOLE DERIVATIVE; SULFONAMIDE; 2 (1H INDAZOL 4 YL) 6 (4 METHANESULFONYLPIPERAZIN 1 YLMETHYL) 4 MORPHOLIN 4 YLTHIENO(3,2 D)PYRIMIDINE; DIAGNOSTIC AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG UPTAKE; ENZYME INHIBITION; GENE OVEREXPRESSION; GLIOMA CELL; LIVER METASTASIS; MOUSE; NONHUMAN; NUDE MOUSE; POSITRON EMISSION TOMOGRAPHY; PREDICTION; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; DIAGNOSTIC USE; DISEASE MODEL; DRUG EFFECTS; DRUG SCREENING; FEMALE; HCT116 CELL LINE; HUMAN; METABOLISM; METASTASIS; NEOPLASMS; TUMOR CELL LINE; TUMOR VOLUME; CELL STRAIN HCT116; DRUG ANTAGONISM; DRUG EFFECT; NEOPLASM;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DIDEOXYNUCLEOSIDES; DISEASE MODELS, ANIMAL; FEMALE; HCT116 CELLS; HUMANS; INDAZOLES; MICE; NEOPLASM METASTASIS; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; POSITRON-EMISSION TOMOGRAPHY; SIGNAL TRANSDUCTION; SULFONAMIDES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84877685163     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: 10.1158/1535-7163.MCT-12-0905     Document Type: Article

References (49)

1. Vanhaesebroeck B, Stephens L, Hawkins P. PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol 2012;13: 195-203.
2. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009;9:550-62.
3. Raynaud FI, Eccles SA, Patel S, Alix S, Box G, Chuckowree I, et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther 2009;8:1725-38.
4. Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl) -4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem 2008;51:5522-32.
5. Weber WA. Monitoring tumor response to therapy with F-18-FLT PET. J Nucl Med 2010;51:841-4.
6. Martin-Fernandez C, Bales J, Hodgkinson C, Welman A, Welham MJ, Dive C, et al. Blocking phosphoinositide 3-kinase activity in colorectal cancer cells reduces proliferation but does not increase apoptosis alone or in combination with cytotoxic drugs. Mol Cancer Res 2009;7:955-65.
7. Workman P, Aboagye EO, Balkwill F, Balmain A, Bruder G, Chaplin DJ, et al. Guidelines for the welfare and use of animals in cancer research. Br J Cancer 2010;102:1555-77.
8. Blocher A, Kuntzsch M, Wei R, Machulla HJ. Synthesis and labeling of 50-O-(4,40-dimethoxytrityl)-2,30-anhydrothymidine for [F-18]FLT preparation. J Radioanal Nucl Chem 2002;251:55-8.
9. Reader AJ, Ally S, Bakatselos F, Manavaki R, Walledge RJ, Jeavons AP, et al. One-pass list-mode EM algorithm for high-resolution 3-D PET image reconstruction into large arrays. IEEE Trans Nucl Sci 2002;49:693-9.
10. Hennig J, Nauerth A, Friedburg H. Rare imaging-a fast imaging method for clinical MR. Magn Reson Med 1986;3:823-33.
11. Burrows N, Resch J, Cowen RL, von Wasielewski R, Hoang-Vu C, West CM, et al. Expression of hypoxia-inducible factor 1 alpha in thyroid carcinomas. Endocr Relate Cancer 2010;17:61-72.
12. Pao W, Chmielecki J. Rational, biologically based treatment of EGFRmutant non-small-cell lung cancer. Nat Rev Cancer 2010;10:760-74.
13. Berndt A, Miller S, Williams O, Le DD, Houseman BT, Pacold JI, et al. The p110 delta structure: mechanisms for selectivity and potency of new PI(3)K inhibitors. Nat Chem Biol 2010;6:117-24.
14. O'Brien C, Wallin JJ, Sampath D, Guha Thakurta D, Savage H, Punnoose EA, et al. Predictive biomarkers of sensitivity to the phosphatidylinositol 3' kinase inhibitor GDC-0941 in breast cancer preclinical models. Clin Cancer Res 2010;16:3670-83.
15. Kong DX, Dan SG, Yamazaki K, Yamori T. Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39. Eur J Cancer 2010;46: 1111-21.
16. Burrows N, Babur M, Resch J, Ridsdale S, Mejin M, Rowling EJ, et al. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxiainducible factor-1 alpha (HIF-1 alpha) pathways. J Clin Endocrinol Metabol 2011;96:E1934-43.
17. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366:883-92.
18. Fuereder T, Wanek T, Pflegerl P, Jaeger-Lansky A, Hoeflmayer D, Strommer S, et al. Gastric cancer growth control by BEZ235 in vivo does not correlate with PI3K/mTOR target inhibition but with [(18)F]FLT uptake. Clin Cancer Res 2011;17:5322-32.
19. Logue JS, Morrison DK. Complexity in the signaling network: insights from the use of targeted inhibitors in cancer therapy. Genes Dev 2012;26:641-50.
20. Herrmann K, Buck AK, Schuster T, Junger A, Wieder HA, Graf N, et al. Predictive value of initial F-18-FLT uptake in patients with aggressive non-hodgkin lymphoma receiving R-CHOP treatment. J Nucl Med 2011;52:690-6.
21. Linecker A, Kermer C, Sulzbacher I, Angelberger P, Kletter K, Dudczak R, et al. Uptake of F-18-FLT and F-18-FDG in primary head and neck cancer correlates with survival. Nuklearmedizin 2008;47:80-5.
22. Zhang CC, Yan ZM, Li WL, Kuszpit K, Painter CL, Zhang Q, et al. [F-18] FLT-PET imaging does not always "Light Up" proliferating tumor cells. Clin Cancer Res 2012;18:1303-12.
23. Moroz MA, Kochetkov T, Cai SD, Wu JY, Shamis M, Nair J, et al. Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of [F-18]fluoro-2-deoxyglucose and 30-deoxy-30-[F-18]fluorothymidine imaging. Clin Cancer Res 2011;17:1099-110.
24. Bayraktar UD, Bayraktar S, Rocha-Lima CM. Molecular basis and management of gastrointestinal stromal tumors. World J Gastroenterol 2010;16:2726-34.
25. Mudd SR, Holich KD, Voorbach MJ, Cole TB, Reuter DR, Tapang P, et al. Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model. Mol Imaging Biol 2012;14:617-24.
26. Lee SJ, Kang HY, Kim SY, Chung JH, Oh SJ, Ryu JS, et al. Early assessment of tumor response to JAC106, an anti-tubulin agent, by 30-deoxy-30-[F-18] fluorothymidine in preclinical tumor models. Eur J Nucl Med Mol Imaging 2011;38:1436-48.
27. Brepoels L, Stroobants S, Verhoef G, De Groot T, Mortelmans L, De Wolf-Peeters C. (18)F-FDG and (18)F-FLT uptake early after cyclophosphamide and mTOR inhibition in an experimental lymphoma model. J Nucl Med 2009;50:1102-9.
28. Ullrich RT, Zander T, Neumaier B, Koker M, Shimamura T, Waerzeggers Y, et al. Early detection of erlotinib treatment response in NSCLC by 30-deoxy-30-[F-18]-fluoro-L-thymidine ([F-18]FLT) positron emission tomography (PET). PLoS One 2008;3:e3908.
29. Wei LH, Su H, Hildebrandt IJ, Phelps ME, Czernin J, Weber WA. Changes in tumor metabolism as readout for mammalian target of rapamycin kinase inhibition by rapamycin in glioblastoma. Clin Cancer Res 2008;14:3416-26.
30. Leyton J, Smith G, Lees M, Perumal M, Nguyen QD, Aigbirhio FI, et al. Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Mol Cancer Ther 2008;7:3112-21.
31. Solit DB, Santos E, Pratilas CA, Lobo J, Moroz M, Cai S, et al. 30-deoxy-30-[(18)F]fluorothymidine positron emission tomography is a sensitive method for imaging the response of BRAF-dependent tumors to MEK inhibition. Cancer Res 2007;67:11463-9.
32. Cullinane C, Dorow DS, Jackson S, Solomon B, Bogatyreva E, Binns D, et al. Differential F-18-FDG and 3 '-deoxy-3 '-F-18-fluorothymidine PET responses to pharmacologic inhibition of the c-MET receptor in preclinical tumor models. J Nucl Med 2011;52:1261-7.
33. 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.
34. Leyton J, Alao JP, Da Costa M, Stavropoulou AV, Latigo JR, Perumal M, et al. In vivo biological activity of the histone deacetylase inhibitor LA0824 is detectable with 30-deoxy-30-[F-18]fluorothymidine positron emission tomography. Cancer Res 2006;66:21-9.
35. Waldherr C, Mellinghoff IK, Tran C, Halpern BS, Rozengurt N, Safaei A, et al. Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 30-deoxy-30-F-18-fluorothymidine PET. J Nucl Med 2005;46:114-20.
36. Barthel H, Cleij MC, Collingridge DR, Hutchinson OC, Osman S, He QM, et al. 30-deoxy-30-[F-18]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res 2003;63:3791-8.
37. Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, Geist C, et al. 30-deoxy-30-F-18-fluorothymidine PET and MRI for early survival predictions in patients with recurrent malignant glioma treated with bevacizumab. J Nucl Med 2012;53:29-36.
38. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008;22:659-61.
39. Basu B, Baird R, Shah K, Banerjee S, Sarker D, Luscombe N, et al. A phase I study evaluating GDC-0941, an oral phosphoinositide-3 kinase (PI3K) inhibitor, in patients (pts) with advanced solid tumors or multiple myeloma. In: National Cancer Research Institute (NCRI) Cancer Conference 2011; 6-9 Nov 2011; Liverpool, UK. NCRI; Nov 2011. Abstract B29.
40. Jensen MM, Erichsen KD, Bjorkling F, Madsen J, Jensen PB, Hojgaard L, et al. Early detection of response to experimental chemotherapeutic Top216 with [F-18]FLT and [F-18]FDG PET in human ovary cancer xenografts in mice. PLoS One 2010;5:e12965.
41. Roberts PJ, Usary JE, Darr DB, Dillon PM, Pfefferle AD, Whittle MC, et al. Combined PI3K/mTOR and MEK inhibition provides broad antitumor activity in faithful murine cancer models. Clin Cancer Res 2012;18:5290-303.
42. Salphati L, Wong H, Belvin M, Bradford D, Edgar KA, Prior WW, et al. Pharmacokinetic-pharmacodynamic modeling of tumor growth inhibition and biomarker modulation by the novel phosphatidylinositol 3-kinase inhibitor GDC-0941. Drug Metab Dispos 2010; 38:1436-42.
43. Matthews DJ, Ventura R, Tai A, Holst C, O'Farrell M. PWT33597 promotes apoptosis in tumor cells through balanced dual inhibition of PI3K alpha and mTOR. In: Proceedings of the AACR-NCI-EORTC International Conference:Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR. Abstract nr B160.
44. Nguyen QD, Perumal M, Waldman TA, Aboagye EO. Glucose metabolism measured by [F-18]fluorodeoxyglucose positron emission tomography is independent of PTEN/AKT status in human colon carcinoma cells. Transl Oncol 2011;4:231-8.
45. Kanematsu M, Kondo H, Goshima S, Kato H, Tsuge U, Hirose Y, et al. Imaging liver metastases: review and update. Eur J Radiol 2006; 58:217-28.
46. Kerbel RS. Human tumor xenografts as predictive preclinical models for anticancer drug activity in humans-Better than commonly perceived-But they can be improved. Cancer Biol Ther 2003;2: S134-9.
47. Lee S, Wong P, Lee ST, Wong P, Muralidharan V, Herbertson R, et al. Non-invasive evaluation of hypoxia using 18F-FMISO PET in liver metastasis from colorectal carcinoma. J Nucl Med 2008;49(Suppl 1):318P.
48. van Laarhoven HWM, Bussink J, Lok J, Verhagen I, Punt CJA, Heerschap A, et al. Modulation of hypoxia in murine liver metastases of colon carcinoma by nicotinamide and carbogen. Radiat Res 2005;164:245-9.
49. Honer M, Ebenhan T, Allegrini PR, Ametamey SM, Becquet M, Cannet C, et al. Anti-angiogenic/vascular effects of the mTOR inhibitor everolimus are not detectable by FDG/FLT-PET. Transl Oncol 2010;3: 264-75.