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Radiopharmaceuticals as probes to characterize tumour tissue

  • Israt S. Alam
  • Mubarik A. Arshad
  • Quang-Dé Nguyen
  • Eric O. AboagyeEmail author
Review Article

Abstract

Tumour cells exhibit several properties that allow them to grow and divide. A number of these properties are detectable by nuclear imaging methods. We discuss crucial tumour properties that can be described by current radioprobe technologies, further discuss areas of emerging radioprobe development, and finally articulate need areas that our field should aspire to develop. The review focuses largely on positron emission tomography and draws upon the seminal ‘Hallmarks of Cancer’ review article by Hanahan and Weinberg in 2011 placing into context the present and future roles of radiotracer imaging in characterizing tumours.

Keywords

Oncology Hallmarks Nuclear imaging Positron emission tomography Radiopharmaceuticals 

References

  1. 1.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRefPubMedGoogle Scholar
  2. 2.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.CrossRefPubMedGoogle Scholar
  3. 3.
    Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 1998;4(11):1334–6.Google Scholar
  4. 4.
    Shields AF, Lawhorn-Crews JM, Briston DA, Zalzala S, Gadgeel S, Douglas KA, et al. Analysis and reproducibility of 3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging in patients with non-small cell lung cancer. Clin Cancer Res. 2008;14(14):4463–8.Google Scholar
  5. 5.
    Paproski RJ, Ng AM, Yao SY, Graham K, Young JD, Cass CE. The role of human nucleoside transporters in uptake of 3'-deoxy-3'-fluorothymidine. Mol Pharmacol. 2008;74(5):1372–80.Google Scholar
  6. 6.
    Seitz U, Wagner M, Neumaier B, Wawra E, Glatting G, Leder G, et al. Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines. Eur J Nucl Med Mol Imaging. 2002;29(9):1174–81.Google Scholar
  7. 7.
    McKinley ET, Ayers GD, Smith RA, Saleh SA, Zhao P, Washington MK, et al. Limits of [18F]-FLT PET as a biomarker of proliferation in oncology. PLoS One. 2013;8(3):e58938.Google Scholar
  8. 8.
    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(5):1303–12.Google Scholar
  9. 9.
    Schelhaas S, Wachsmuth L, Viel T, Honess DJ, Heinzmann K, Smith DM, 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(6):983–8.Google Scholar
  10. 10.
    Leyton J, Alao JP, Da Costa M, Stavropoulou AV, Latigo JR, Perumal M, et al. In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography. Cancer Res. 2006;66(15):7621–9.Google Scholar
  11. 11.
    Barwick T, Bencherif B, Mountz JM, Avril N. Molecular PET and PET/CT imaging of tumour cell proliferation using F-18 fluoro-L-thymidine: a comprehensive evaluation. Nucl Med Commun. 2009;30(12):908–17.Google Scholar
  12. 12.
    Dittmann H, Dohmen BM, Paulsen F, Eichhorn K, Eschmann SM, Horger M, et al. [18F]FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging. 2003;30(10):1407–12.Google Scholar
  13. 13.
    Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, et al. Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med. 2003;44(9):1426–31.Google Scholar
  14. 14.
    Cobben DC, Jager PL, Elsinga PH, Maas B, Suurmeijer AJ, Hoekstra HJ. 3'-18Ffluoro-3'-deoxy-L-thymidine: a new tracer for staging metastatic melanoma? J Nucl Med. 2003;44(12):1927–32.Google Scholar
  15. 15.
    Smyczek-Gargya B, Fersis N, Dittmann H, Vogel U, Reischl G, Machulla HJ, et al. PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging. 2004;31(5):720–4.Google Scholar
  16. 16.
    van Westreenen HL, Cobben DC, Jager PL, van Dullemen HM, Wesseling J, Elsinga PH, et al. Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer. J Nucl Med. 2005;46(3):400–4.Google Scholar
  17. 17.
    Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, et al. Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG. J Nucl Med. 2005;46(6):945–52.Google Scholar
  18. 18.
    Yamamoto Y, Nishiyama Y, Kimura N, Ishikawa S, Okuda M, Bandoh S, et al. Comparison of (18)F-FLT PET and (18)F-FDG PET for preoperative staging in non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2008;35(2):236–45.Google Scholar
  19. 19.
    Yamamoto Y, Nishiyama Y, Ishikawa S, Nakano J, Chang SS, Bandoh S, et al. Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2007;34(10):1610–6.Google Scholar
  20. 20.
    Yamane T, Takaoka A, Kita M, Imai Y, Senda M. 18F-FLT PET performs better than 18F-FDG PET in differentiating malignant uterine corpus tumors from benign leiomyoma. Ann Nucl Med. 2012;26(6):478–84.Google Scholar
  21. 21.
    Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3'-[F-18]fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol. 2006;8(1):36–42.Google Scholar
  22. 22.
    Kenny L, Coombes RC, Vigushin DM, Al-Nahhas A, Shousha S, Aboagye EO. Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography. Eur J Nucl Med Mol Imaging. 2007;34(9):1339–47.Google Scholar
  23. 23.
    Trigonis I, Koh PK, Taylor B, Tamal M, Ryder D, Earl M, et al. Early reduction in tumour [(18)F]fluorothymidine (FLT) uptake in patients with non-small cell lung cancer (NSCLC) treated with radiotherapy alone. Eur J Nucl Med Mol Imaging. 2014;41(4):682–93.Google Scholar
  24. 24.
    Contractor K, Challapalli A, Barwick T, Winkler M, Hellawell G, Hazell S, et al. Use of [11C]choline PET-CT as a noninvasive method for detecting pelvic lymph node status from prostate cancer and relationship with choline kinase expression. Clin Cancer Res. 2011;17(24):7673–83.Google Scholar
  25. 25.
    Ayala-Peacock DN, Thomas AJ, Smith H, Garg P, Blackstock AW. A pilot 11C-choline PET-CT imaging study in patients with locally advanced esophageal cancer. Pract Radiat Oncol. 2013;3(2 Suppl 1):S23.Google Scholar
  26. 26.
    Castellucci P, Ceci F, Graziani T, Schiavina R, Brunocilla E, Mazzarotto R, et al. Early biochemical relapse after radical prostatectomy: which prostate cancer patient may benefit from a restaging 11C-choline PET/CT scan before salvage radiation therapy? J Nucl Med. 2014.Google Scholar
  27. 27.
    Garcia JR, Jorcano S, Soler M, Linero D, Moragas M, Riera E, et al. 11C-choline PET/CT in the primary diagnosis of prostate cancer: impact on treatment planning. Q J Nucl Med Mol Imaging. 2014.Google Scholar
  28. 28.
    Picchio M, Berardi G, Fodor A, Busnardo E, Crivellaro C, Giovacchini G, et al. (11)CCholine PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2014;41(7):1270–9.Google Scholar
  29. 29.
    Umbehr MH, Muntener M, Hany T, Sulser T, Bachmann LM. The role of 11C-choline and 18F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol. 2013;64(1):106–17.Google Scholar
  30. 30.
    Poulsen MH, et al. [18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients. BJU Int. 2012;110(11):1666–71.CrossRefPubMedGoogle Scholar
  31. 31.
    Poulsen MH, Petersen H, Hoilund-Carlsen PF, Jakobsen JS, Gerke O, Karstoft J, et al. Spine metastases in prostate cancer: comparison of [ Tc]MDP wholebody bone scintigraphy, [ F]choline PET/CT, and [ F]NaF PET/CT. BJU Int. 2013.Google Scholar
  32. 32.
    Piccardo A, Paparo F, Picazzo R, Naseri M, Ricci P, Marziano A, et al. Value of fused (18) F-choline-PET/MRI to evaluate prostate cancer relapse in patients showing biochemical recurrence after EBRT: preliminary results. Biomed Res Int. 2014;2014:103718.Google Scholar
  33. 33.
    Challapalli A, Sharma R, Hallett WA, Kozlowski K, Carroll L, Brickute D, et al. Biodistribution and radiation dosimetry of deuterium-substituted 18F-fluoromethyl-[1, 2-2H4]choline in healthy volunteers. J Nucl Med. 2014;55(2):256–63.Google Scholar
  34. 34.
    Heukelom J, Hamming O, Bartelink H, Hoebers F, Giralt J, Herlestam T, et al. Adaptive and innovative Radiation Treatment FOR improving Cancer treatment outcomE (ARTFORCE); a randomized controlled phase II trial for individualized treatment of head and neck cancer. BMC Cancer. 2013;13:84.Google Scholar
  35. 35.
    Tsujikawa T, Yoshida Y, Kiyono Y, Kurokawa T, Kudo T, Fujibayashi Y, et al. Functional oestrogen receptor alpha imaging in endometrial carcinoma using 16alpha-[(1)(8)F]fluoro-17beta-oestradiol PET. Eur J Nucl Med Mol Imaging. 2011;38(1):37–45.Google Scholar
  36. 36.
    Zhao Z, Yoshida Y, Kurokawa T, Kiyono Y, Mori T, Okazawa H. 18F-FES and 18F-FDG PET for differential diagnosis and quantitative evaluation of mesenchymal uterine tumors: correlation with immunohistochemical analysis. J Nucl Med. 2013;54(4):499–506.Google Scholar
  37. 37.
    Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 2010;87(5):586–92.Google Scholar
  38. 38.
    Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Loidl W, et al. Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study. Eur J Nucl Med Mol Imaging. 2008;35(10):1766–74.Google Scholar
  39. 39.
    Withofs N, Grayet B, Tancredi T, Rorive A, Mella C, Giacomelli F, et al. (1)(8)F-fluoride PET/CT for assessing bone involvement in prostate and breast cancers. Nucl Med Commun. 2011;32(3):168–76.Google Scholar
  40. 40.
    Gaykema SB, Brouwers AH, Lub-de Hooge MN, Pleijhuis RG, Timmer-Bosscha H, Pot L, et al. 89Zr-bevacizumab PET imaging in primary breast cancer. J Nucl Med. 2013;54(7):1014–8.Google Scholar
  41. 41.
    Ng CS, Kodama Y, Mullani NA, Barron BJ, Wei W, Herbst RS, et al. Tumor blood flow measured by perfusion computed tomography and 15O-labeled water positron emission tomography: a comparison study. J Comput Assist Tomogr. 2009;33(3):460–5.Google Scholar
  42. 42.
    Scott AM, Mitchell PL, O’Keefe G, Saunder T, Hicks RJ, Poon A, et al. Pharmacodynamic analysis of tumour perfusion assessed by 15O-water-PET imaging during treatment with sunitinib malate in patients with advanced malignancies. EJNMMI Res. 2012;2(1):31.Google Scholar
  43. 43.
    Kurdziel KA, Figg WD, Carrasquillo JA, Huebsch S, Whatley M, Sellers D, et al. Using positron emission tomography 2-deoxy-2-[18F]fluoro-D-glucose, 11CO, and 15O-water for monitoring androgen independent prostate cancer. Mol Imaging Biol. 2003;5(2):86–93.Google Scholar
  44. 44.
    Beer AJ, Grosu AL, Carlsen J, Kolk A, Sarbia M, Stangier I, et al. [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2007;13(22 Pt 1):6610–6.Google Scholar
  45. 45.
    Beer AJ, Lorenzen S, Metz S, Herrmann K, Watzlowik P, Wester HJ, et al. Comparison of integrin alphaVbeta3 expression and glucose metabolism in primary and metastatic lesions in cancer patients: a PET study using 18F-galacto-RGD and 18F-FDG. J Nucl Med. 2008;49(1):22–9.Google Scholar
  46. 46.
    Tomasi G, Kenny L, Mauri F, Turkheimer F, Aboagye EO. Quantification of receptorligand binding with [(1)(8)F]fluciclatide in metastatic breast cancer patients. Eur J Nucl Med Mol Imaging. 2011;38(12):2186–97.Google Scholar
  47. 47.
    Doss M, Kolb HC, Zhang JJ, Belanger MJ, Stubbs JB, Stabin MG, et al. Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans. J Nucl Med. 2012;53(5):787–95.Google Scholar
  48. 48.
    Brouwers AH, Dorr U, Lang O, Boerman OC, Oyen WJ, Steffens MG, et al. 131 I-cG250 monoclonal antibody immunoscintigraphy versus [18F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative study. Nucl Med Commun. 2002;23(3):229–36.Google Scholar
  49. 49.
    Divgi CR, Uzzo RG, Gatsonis C, Bartz R, Treutner S, Yu JQ, et al. Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. J Clin Oncol. 2013;31(2):187–94.Google Scholar
  50. 50.
    Gagel B, Reinartz P, Demirel C, Kaiser HJ, Zimny M, Piroth M, et al. [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study. BMC Cancer. 2006;6:51.Google Scholar
  51. 51.
    Hugonnet F, Fournier L, Medioni J, Smadja C, Hindie E, Huchet V, et al. Metastatic renal cell carcinoma: relationship between initial metastasis hypoxia, change after 1month’s sunitinib, and therapeutic response: an 18F-fluoromisonidazole PET/CT study. J Nucl Med. 2011;52(7):1048–55.Google Scholar
  52. 52.
    Segard T, Robins PD, Yusoff IF, Ee H, Morandeau L, Campbell EM, et al. Detection of hypoxia with 18F-fluoromisonidazole (18F-FMISO) PET/CT in suspected or proven pancreatic cancer. Clin Nucl Med. 2013;38(1):1–6.Google Scholar
  53. 53.
    Tachibana I, Nishimura Y, Shibata T, Kanamori S, Nakamatsu K, Koike R, et al. A prospective clinical trial of tumor hypoxia imaging with 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) before and during radiation therapy. J Radiat Res. 2013;54(6):1078–84.Google Scholar
  54. 54.
    Grassi I, Nanni C, Cicoria G, Blasi C, Bunkheila F, Lopci E, et al. Usefulness of 64Cu-ATSM in head and neck cancer: a preliminary prospective study. Clin Nucl Med. 2014;39(1):e59–63.Google Scholar
  55. 55.
    Garcia-Parra R, Wood D, Shah RB, Siddiqui J, Hussain H, Park H, et al. Investigation on tumor hypoxia in resectable primary prostate cancer as demonstrated by 18F-FAZA PET/CT utilizing multimodality fusion techniques. Eur J Nucl Med Mol Imaging. 2011;38(10):1816–23.Google Scholar
  56. 56.
    Bollineni VR, Kerner GS, Pruim J, Steenbakkers RJ, Wiegman EM, Koole MJ, et al. PET imaging of tumor hypoxia using 18F-fluoroazomycin arabinoside in stage III-IV non-small cell lung cancer patients. J Nucl Med. 2013;54(8):1175–80.Google Scholar
  57. 57.
    Havelund BM, Holdgaard PC, Rafaelsen SR, Mortensen LS, Theil J, Bender D, et al. Tumour hypoxia imaging with 18F-fluoroazomycinarabinofuranoside PET/CT in patients with locally advanced rectal cancer. Nucl Med Commun. 2013;34(2):155–61.Google Scholar
  58. 58.
    Trinkaus ME, Blum R, Rischin D, Callahan J, Bressel M, Segard T, et al. Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy. J Med Imaging Radiat Oncol. 2013;57(4):475–81.Google Scholar
  59. 59.
    Beer AJ, Niemeyer M, Carlsen J, Sarbia M, Nahrig J, Watzlowik P, et al. Patterns of alphavbeta3 expression in primary and metastatic human breast cancer as shown by 18FGalacto-RGD PET. J Nucl Med. 2008;49(2):255–9.Google Scholar
  60. 60.
    Chen L, Zhang Z, Kolb HC, Walsh JC, Zhang J, Guan Y. (1)(8)F-HX4 hypoxia imaging with PET/CT in head and neck cancer: a comparison with (1)(8)F-FMISO. Nucl Med Commun. 2012;33(10):1096–102.Google Scholar
  61. 61.
    Zegers CM, van Elmpt W, Wierts R, Reymen B, Sharifi H, Ollers MC, et al. Hypoxia imaging with [(1)(8)F]HX4 PET in NSCLC patients: defining optimal imaging parameters. Radiother Oncol. 2013;109(1):58–64.Google Scholar
  62. 62.
    Doss M, Kolb HC, Walsh JC, Mocharla VP, Zhu Z, Haka M, et al. Biodistribution and radiation dosimetry of the carbonic anhydrase IX imaging agent [ F]VM4-037 determined from PET/CT scans in healthy volunteers. Mol Imaging Biol. 2014;16(5):739–46.Google Scholar
  63. 63.
    Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Cavalho S, et al. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nat Commun. 2014;5:4006.Google Scholar
  64. 64.
    Belhocine T, Steinmetz N, Hustinx R, Bartsch P, Jerusalem G, Seidel L, et al. Increased uptake of the apoptosis-imaging agent (99m)Tc recombinant human Annexin V in human tumors after one course of chemotherapy as a predictor of tumor response and patient prognosis. Clin Cancer Res. 2002;8(9):2766–74.Google Scholar
  65. 65.
    Haas RL, de Jong D, Valdes Olmos RA, Hoefnagel CA, van den Heuvel I, Zerp SF, et al. In vivo imaging of radiation-induced apoptosis in follicular lymphoma patients. Int J Radiat Oncol Biol Phys. 2004;59(3):782–7.Google Scholar
  66. 66.
    Kartachova M, Haas RL, Olmos RA, Hoebers FJ, van Zandwijk N, Verheij M. In vivo imaging of apoptosis by 99mTc-Annexin V scintigraphy: visual analysis in relation to treatment response. Radiother Oncol. 2004;72(3):333–9.Google Scholar
  67. 67.
    Hoebers FJ, Kartachova M, de Bois J, van den Brekel MW, van Tinteren H, van Herk M, et al. 99mTc Hynic-rh-Annexin V scintigraphy for in vivo imaging of apoptosis in patients with head and neck cancer treated with chemoradiotherapy. Eur J Nucl Med Mol Imaging. 2008;35(3):509–18.Google Scholar
  68. 68.
    Allen AM, Ben-Ami M, Reshef A, Steinmetz A, Kundel Y, Inbar E, et al. Assessment of response of brain metastases to radiotherapy by PET imaging of apoptosis with (1)(8)F-ML-10. Eur J Nucl Med Mol Imaging. 2012;39(9):1400–8.Google Scholar
  69. 69.
    Challapalli A, Kenny LM, Hallett WA, Kozlowski K, Tomasi G, Gudi M, et al. 18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and radiation dosimetry. J Nucl Med. 2013;54(9):1551–6.Google Scholar
  70. 70.
    Doss M, Kolb HC, Walsh JC, Mocharla V, Fan H, Chaudhary A, et al. Biodistribution and radiation dosimetry of 18F-CP-18, a potential apoptosis imaging agent, as determined from PET/CT scans in healthy volunteers. J Nucl Med. 2013;54(12):2087–92.Google Scholar
  71. 71.
    Orevi M, Klein M, Mishani E, Chisin R, Freedman N, Gofrit ON. 11C-acetate PET/CT in bladder urothelial carcinoma: intraindividual comparison with 11C-choline. Clin Nucl Med. 2012;37(4):e67–72.Google Scholar
  72. 72.
    Cheung TT, Ho CL, Lo CM, Chen S, Chan SC, Chok KS, et al. 11C-acetate and 18F-FDG PET/CT for clinical staging and selection of patients with hepatocellular carcinoma for liver transplantation on the basis of Milan criteria: surgeon’s perspective. J Nucl Med. 2013;54(2):192–200.Google Scholar
  73. 73.
    Oyama N, Ito H, Aoki Y, Miwa Y, Akino H, Kudo T, et al. Carbon-11-acetate positron emission tomography (PET), versus fluorine- 18 fluorodeoxyglucose PET and CT for the diagnosis of recurrent prostate cancer after radical prostatectomy in cases of prostate specific antigen of more than 1 to 3 ng/mL. Hell J Nucl Med. 2013;16(2):146–7.Google Scholar
  74. 74.
    Wahl RL, Quint LE, Greenough RL, Meyer CR, White RI, Orringer MB. Staging of mediastinal non-small cell lung cancer with FDG PET, CT, and fusion images: preliminary prospective evaluation. Radiology. 1994;191(2):371–7.Google Scholar
  75. 75.
    Wong WL, Hussain K, Chevretton E, Hawkes DJ, Baddeley H, Maisey M, et al. Validation and clinical application of computer-combined computed tomography and positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose head and neck images. Am J Surg. 1996;172(6):628–32.Google Scholar
  76. 76.
    Hoh CK, Glaspy J, Rosen P, Dahlbom M, Lee SJ, Kunkel L, et al. Whole-body FDG-PET imaging for staging of Hodgkin’s disease and lymphoma. J Nucl Med. 1997;38(3):343–8.Google Scholar
  77. 77.
    Mattei R, Rubello D, Ferlin G, Bagatella F. Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) in the diagnosis and preoperative staging of head and neck tumors: a prospective study. Acta Otorhinolaryngol Ital. 1998;18(6):387–91.Google Scholar
  78. 78.
    Kole AC, Plukker JT, Nieweg OE, Vaalburg W. Positron emission tomography for staging of oesophageal and gastroesophageal malignancy. Br J Cancer. 1998;78(4):521–7.Google Scholar
  79. 79.
    Mikhaeel NG, Timothy AR, O’Doherty MJ, Hain S, Maisey MN. 18-FDG-PET as a prognostic indicator in the treatment of aggressive Non-Hodgkin’s Lymphoma-comparison with CT. Leuk Lymphoma. 2000;39(5–6):543–53.Google Scholar
  80. 80.
    Larson SM, Morris M, Gunther I, Beattie B, Humm JL, Akhurst TA, et al. Tumor localization of 16beta-18F-fluoro-5alpha-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med. 2004;45(3):366–73.Google Scholar
  81. 81.
    Vargas HA, Wassberg C, Fox JJ, Wibmer A, Goldman DA, Kuk D, et al. Bone metastases in castration-resistant prostate cancer: associations between morphologic CT patterns, glycolytic activity, and androgen receptor expression on PET and overall survival. Radiology. 2014;271(1):220–9.Google Scholar
  82. 82.
    Dehdashti F, Laforest R, Gao F, Shoghi KI, Aft RL, Nussenbaum B, et al. Assessment of cellular proliferation in tumors by PET using 18F-ISO-1. J Nucl Med. 2013;54(3):350–7.Google Scholar
  83. 83.
    Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48(4):508–18.Google Scholar
  84. 84.
    Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer. 2008;112(11):2447–55.Google Scholar
  85. 85.
    Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol. 2014;55(4):389–98.Google Scholar
  86. 86.
    Hoegerle S, Altehoefer C, Ghanem N, Koehler G, Waller CF, Scheruebl H, et al. Wholebody 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology. 2001;220(2):373–80.Google Scholar
  87. 87.
    Ambrosini V, Tomassetti P, Rubello D, Campana D, Nanni C, Castellucci P, et al. Role of 18F-dopa PET/CT imaging in the management of patients with 111In-pentetreotide negative GEP tumours. Nucl Med Commun. 2007;28(6):473–7.Google Scholar
  88. 88.
    Beheshti M, Pocher S, Vali R, Waldenberger P, Broinger G, Nader M, et al. The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Eur Radiol. 2009;19(6):1425–34.Google Scholar
  89. 89.
    Matsuo M, Miwa K, Tanaka O, Shinoda J, Nishibori H, Tsuge Y, et al. Impact of [11C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys. 2012;82(1):83–9.Google Scholar
  90. 90.
    Shiiba M, Ishihara K, Kimura G, Kuwako T, Yoshihara H, Sato H, et al. Evaluation of primary prostate cancer using 11C-methionine-PET/CT and 18F-FDG-PET/CT. Ann Nucl Med. 2012;26(2):138–45.Google Scholar
  91. 91.
    Singhal T, Narayanan TK, Jacobs MP, Bal C, Mantil JC. 11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI. J Nucl Med. 2012;53(11):1709–15.Google Scholar
  92. 92.
    Tomura N, Ito Y, Matsuoka H, Saginoya T, Numazawa SI, Mizuno Y, et al. PET findings of intramedullary tumors of the spinal cord using [18F] FDG and [11C] methionine. AJNR Am J Neuroradiol. 2013;34(6):1278–83.Google Scholar
  93. 93.
    Nanni C, Schiavina R, Brunocilla E, Borghesi M, Ambrosini V, Zanoni L, et al. 18F-FACBC Compared With 11C-Choline PET/CT in Patients With Biochemical Relapse After Radical Prostatectomy: A Prospective Study in 28 Patients. Clin Genitourin Cancer. 2014;12(2):106–10.Google Scholar
  94. 94.
    Hennings J, Lindhe O, Bergstrom M, Langstrom B, Sundin A, Hellman P. [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings. J Clin Endocrinol Metab. 2006;91(4):1410–4.Google Scholar
  95. 95.
    Roivainen A, Naum A, Nuutinen H, Leino R, Nurmi H, Nagren K, et al. Characterization of hepatic tumors using [11C]metomidate through positron emission tomography: comparison with [11C]acetate. EJNMMI Res. 2013;3(1):13.Google Scholar
  96. 96.
    Sohn HJ, Yang YJ, Ryu JS, Oh SJ, Im KC, Moon DH, et al. [18F]Fluorothymidine positron emission tomography before and 7 days after gefitinib treatment predicts response in patients with advanced adenocarcinoma of the lung. Clin Cancer Res. 2008;14(22):7423–9.Google Scholar
  97. 97.
    Schwarzenberg J, Czernin J, Cloughesy TF, Ellingson BM, Pope WB, 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(1):29–36.Google Scholar
  98. 98.
    Mishani E, Abourbeh G, Eiblmaier M, Anderson CJ. Imaging of EGFR and EGFR tyrosine kinase overexpression in tumors by nuclear medicine modalities. Curr Pharm Des. 2008;14(28):2983–98.Google Scholar
  99. 99.
    Meng X, Loo Jr BW, Ma L, Murphy JD, Sun X, Yu J. Molecular imaging with 11CPD153035 PET/CT predicts survival in non-small cell lung cancer treated with EGFR-TKI: a pilot study. J Nucl Med. 2011;52(10):1573–9.Google Scholar
  100. 100.
    Evans HL, Nguyen QD, Carroll LS, Kaliszczak M, Twyman FJ, Spivey AC, et al. A bioorthogonal (68)Ga-labelling strategy for rapid in vivo imaging. Chem Commun (Camb). 2014;50(67):9557–60.Google Scholar
  101. 101.
    Pal A, Balatoni JA, Mukhopadhyay U, Ogawa K, Gonzalez-Lepera C, Shavrin A, et al. Radiosynthesis and initial in vitro evaluation of [18F]F-PEG6-IPQA–a novel PET radiotracer for imaging EGFR expression-activity in lung carcinomas. Mol Imaging Biol. 2011;13(5):853–61.Google Scholar
  102. 102.
    Tian M, Ogawa K, Wendt R, Mukhopadhyay U, Balatoni J, Fukumitsu N, et al. Wholebody biodistribution kinetics, metabolism, and radiation dosimetry estimates of 18F-PEG6-IPQA in nonhuman primates. J Nucl Med. 2011;52(6):934–41.Google Scholar
  103. 103.
    Yeh HH, Ogawa K, Balatoni J, Mukhapadhyay U, Pal A, Gonzalez-Lepera C, et al. Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT. Proc Natl Acad Sci U S A. 2011;108(4):1603–8.Google Scholar
  104. 104.
    Tamura K, Kurihara H, Yonemori K, Tsuda H, Suzuki J, Kono Y, et al. 64Cu-DOTAtrastuzumab PET imaging in patients with HER2-positive breast cancer. J Nucl Med. 2013;54(11):1869–75.Google Scholar
  105. 105.
    Beylergil V, Morris PG, Smith-Jones PM, Modi S, Solit D, Hudis CA, et al. Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer. Nucl Med Commun. 2013;34(12):1157–65.Google Scholar
  106. 106.
    Trousil S, Hoppmann S, Nguyen QD, Kaliszczak M, Tomasi G, Iveson P, et al. Positron emission tomography imaging with 18F-labeled ZHER2:2891 affibody for detection of HER2 expression and pharmacodynamic response to HER2-modulating therapies. Clin Cancer Res. 2014;20(6):1632–43.Google Scholar
  107. 107.
    Sorensen J, Sandberg D, Sandstrom M, Wennborg A, Feldwisch J, Tolmachev V, et al. First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule. J Nucl Med. 2014;55(5):730–5.Google Scholar
  108. 108.
    van Kruchten M, Glaudemans AW, de Vries EF, Beets-Tan RG, Schroder CP, Dierckx RA, et al. PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma. J Nucl Med. 2012;53(2):182–90.Google Scholar
  109. 109.
    Linden HM, Stekhova SA, Link JM, Gralow JR, Livingston RB, Ellis GK, et al. Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer. J Clin Oncol. 2006;24(18):2793–9.Google Scholar
  110. 110.
    Dorr JR, Yu Y, Milanovic M, Beuster G, Zasada C, Dabritz JH, et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature. 2013;501(7467):421–5.Google Scholar
  111. 111.
    Witney TH, Carroll L, Alam IS, Chandrashekran A, Nguyen QD, Sala R, et al. A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography. Cancer Res. 2014;74(5):1319–28.Google Scholar
  112. 112.
    Gunes C, Rudolph KL. The role of telomeres in stem cells and cancer. Cell. 2013;152(3):390–3.Google Scholar
  113. 113.
    Bernardes de Jesus B, Blasco MA. Telomerase at the intersection of cancer and aging. Trends Genet. 2013;29(9):513–20.Google Scholar
  114. 114.
    Liu M, Wang RF, Yan P, Zhang CL, Cui YG. Molecular imaging and pharmacokinetics of (99m) Tc-hTERT antisense oligonucleotide as a potential tumor imaging probe. J Label Compd Radiopharm. 2014;57(2):97–101.Google Scholar
  115. 115.
    Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12(2):133–43.Google Scholar
  116. 116.
    Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138(4):645–59.Google Scholar
  117. 117.
    Gaedicke S, Braun F, Prasad S, Machein M, Firat E, Hettich M, et al. Noninvasive positron emission tomography and fluorescence imaging of CD133+ tumor stem cells. Proc Natl Acad Sci U S A. 2014;111(6):E692–701.Google Scholar
  118. 118.
    Grosse-Gehling P, Fargeas CA, Dittfeld C, Garbe Y, Alison MR, Corbeil D, et al. CD133 as a biomarker for putative cancer stem cells in solid tumours: limitations, problems and challenges. J Pathol. 2013;229(3):355–78.Google Scholar
  119. 119.
    Mak AB, Blakely KM, Williams RA, Penttila PA, Shukalyuk AI, Osman KT, et al. CD133 protein N-glycosylation processing contributes to cell surface recognition of the primitive cell marker AC133 epitope. J Biol Chem. 2011;286(47):41046–56.Google Scholar
  120. 120.
    Jaggupilli A, Elkord E. Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol. 2012;2012:708036.Google Scholar
  121. 121.
    Nguyen QD, Smith G, Glaser M, Perumal M, Arstad E, Aboagye EO. Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [18F]-labeled isatin sulfonamide. Proc Natl Acad Sci U S A. 2009;106(38):16375–80.Google Scholar
  122. 122.
    Nguyen QD, Lavdas I, Gubbins J, Smith G, Fortt R, Carroll LS, et al. Temporal and spatial evolution of therapy-induced tumor apoptosis detected by caspase-3-selective molecular imaging. Clin Cancer Res. 2013;19(14):3914–24.Google Scholar
  123. 123.
    Nguyen QD, Challapalli A, Smith G, Fortt R, Aboagye EO. Imaging apoptosis with positron emission tomography: ‘bench to bedside’ development of the caspase-3/7 specific radiotracer [(18)F]ICMT-11. Eur J Cancer. 2012;48(4):432–40.Google Scholar
  124. 124.
    Bauwens M, De Saint-Hubert M, Cleynhens J, Vandeputte C, Li J, Devos E. In vitro and in vivo comparison of 18F and 123I-labeled ML10 with 68Ga-Cys2-AnxA5 for molecular imaging of apoptosis. Q J Nucl Med Mol Imaging. 2013;57(2):187–200.Google Scholar
  125. 125.
    Boersma HH, Liem IH, Kemerink GJ, Thimister PW, Hofstra L, Stolk LM, et al. Comparison between human pharmacokinetics and imaging properties of two conjugation methods for 99mTc-annexin A5. Br J Radiol. 2003;76(908):553–60.Google Scholar
  126. 126.
    Kartachova MS, Valdes Olmos RA, Haas RL, Hoebers FJ, van Herk M, Verheij M. 99mTc-HYNIC-rh-annexin-V scintigraphy: visual and quantitative evaluation of early treatment-induced apoptosis to predict treatment outcome. Nucl Med Commun. 2008;29(1):39–44.Google Scholar
  127. 127.
    Lederle W, Arns S, Rix A, Gremse F, Doleschel D, Schmaljohann J, et al. Failure of annexin-based apoptosis imaging in the assessment of antiangiogenic therapy effects. EJNMMI Res. 2011;1(1):26.Google Scholar
  128. 128.
    Alam IS, Neves AA, Witney TH, Boren J, Brindle KM. Comparison of the C2A domain of synaptotagmin-I and annexin-V as probes for detecting cell death. Bioconjug Chem. 2010;21(5):884–91.Google Scholar
  129. 129.
    Grierson JR, Yagle KJ, Eary JF, Tait JF, Gibson DF, Lewellen B, et al. Production of [F-18]fluoroannexin for imaging apoptosis with PET. Bioconjug Chem. 2004;15(2):373–9.Google Scholar
  130. 130.
    Yagle KJ, Eary JF, Tait JF, Grierson JR, Link JM, Lewellen B, et al. Evaluation of 18Fannexin V as a PET imaging agent in an animal model of apoptosis. J Nucl Med. 2005;46(4):658–66.Google Scholar
  131. 131.
    Wang F, Fang W, Zhang MR, Zhao M, Liu B, Wang Z, et al. Evaluation of chemotherapy response in VX2 rabbit lung cancer with 18F-labeled C2A domain of synaptotagmin I. J Nucl Med. 2011;52(4):592–9.Google Scholar
  132. 132.
    Hoglund J, Shirvan A, Antoni G, Gustavsson SA, Langstrom B, Ringheim A, et al. 18F-ML-10, a PET tracer for apoptosis: first human study. J Nucl Med. 2011;52(5):720–5.Google Scholar
  133. 133.
    White E, DiPaola RS. The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 2009;15(17):5308–16.CrossRefPubMedCentralPubMedGoogle Scholar
  134. 134.
    Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86(3):353–64.Google Scholar
  135. 135.
    Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res. 2006;12(13):3942–9.Google Scholar
  136. 136.
    Pohle K, Notni J, Bussemer J, Kessler H, Schwaiger M, Beer AJ. 68Ga-NODAGA-RGD is a suitable substitute for (18)F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process. Nucl Med Biol. 2012;39(6):777–84.Google Scholar
  137. 137.
    Kenny LM, Coombes RC, Oulie I, Contractor KB, Miller M, Spinks TJ, et al. Phase I trial of the positron-emitting Arg-Gly-Asp (RGD) peptide radioligand 18F-AH111585 in breast cancer patients. J Nucl Med. 2008;49(6):879–86.Google Scholar
  138. 138.
    Aboagye EO, Gilbert FJ, Fleming IN, Beer AJ, Cunningham VJ, Marsden PK, et al. Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials. Eur Radiol. 2012;22(7):1465–78.Google Scholar
  139. 139.
    Herbst RS, Mullani NA, Davis DW, Hess KR, McConkey DJ, Charnsangavej C, et al. Development of biologic markers of response and assessment of antiangiogenic activity in a clinical trial of human recombinant endostatin. J Clin Oncol. 2002;20(18):3804–14.Google Scholar
  140. 140.
    Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol. 2013;31(17):2205–18.Google Scholar
  141. 141.
    Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307(5706):58–62.Google Scholar
  142. 142.
    Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11(1):83–95.Google Scholar
  143. 143.
    Sahai E. Mechanisms of cancer cell invasion. Curr Opin Genet Dev. 2005;15(1):87–96.CrossRefPubMedGoogle Scholar
  144. 144.
    Pinner S, Sahai E. Imaging amoeboid cancer cell motility in vivo. J Microsc. 2008;231(3):441–5.CrossRefPubMedGoogle Scholar
  145. 145.
    Hanaoka H, Mukai T, Tamamura H, Mori T, Ishino S, Ogawa K, et al. Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors. Nucl Med Biol. 2006;33(4):489–94.Google Scholar
  146. 146.
    Gourni E, Demmer O, Schottelius M, D’Alessandria C, Schulz S, Dijkgraaf I, et al. PET of CXCR4 expression by a (68)Ga-labeled highly specific targeted contrast agent. J Nucl Med. 2011;52(11):1803–10.Google Scholar
  147. 147.
    Nimmagadda S, Pullambhatla M, Stone K, Green G, Bhujwalla ZM, Pomper MG. Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography. Cancer Res. 2010;70(10):3935–44.Google Scholar
  148. 148.
    Jacobson O, Weiss ID, Szajek L, Farber JM, Kiesewetter DO. 64Cu-AMD3100–a novel imaging agent for targeting chemokine receptor CXCR4. Bioorg Med Chem. 2009;17(4):1486–93.Google Scholar
  149. 149.
    De Silva RA, Peyre K, Pullambhatla M, Fox JJ, Pomper MG, Nimmagadda S. Imaging CXCR4 expression in human cancer xenografts: evaluation of monocyclam 64Cu-AMD3465. J Nucl Med. 2011;52(6):986–93.Google Scholar
  150. 150.
    Lim YC, Han JH, Kang HJ, Kim YS, Lee BH, Choi EC, et al. Overexpression of c-Met promotes invasion and metastasis of small oral tongue carcinoma. Oral Oncol. 2012;48(11):1114–9.Google Scholar
  151. 151.
    Evans P, Battle M, Getvoldsen G, McRobbie G, Bjerke R, Morrison M, et al. Nonclinical tumor efficacy studies of [18F]AH113804, a novel PET imaging agent with high affinity for the human c-Met receptor. Proceedings of the AACR 103rd Annual Meeting 2012. 31 Mar – 4 Apr 2012, Chicago, IL.Google Scholar
  152. 152.
    Lindhe O, T A, A G, I B, E P, M M, et al. PET imaging of c-Met expression in non-human primates using [18F]AH113804. Proceedings of the AACR 103rd Annual Meeting 2012. 31 Mar – 4 Apr 2012, Chicago, IL.Google Scholar
  153. 153.
    Luoto KR, Kumareswaran R, Bristow RG. Tumor hypoxia as a driving force in genetic instability. Genome Integr. 2013;4(1):5.Google Scholar
  154. 154.
    Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer. 2011;11(6):393–410.CrossRefPubMedGoogle Scholar
  155. 155.
    Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26(2):225–39.CrossRefPubMedGoogle Scholar
  156. 156.
    Cheng J, Lei L, Xu J, Sun Y, Zhang Y, Wang X, et al. 18F-fluoromisonidazole PET/CT: a potential tool for predicting primary endocrine therapy resistance in breast cancer. J Nucl Med. 2013;54(3):333–40.Google Scholar
  157. 157.
    Lehtio K, Oikonen V, Nyman S, Gronroos T, Roivainen A, Eskola O, et al. Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio. Eur J Nucl Med Mol Imaging. 2003;30(1):101–8.Google Scholar
  158. 158.
    Barthel H, Wilson H, Collingridge DR, Brown G, Osman S, Luthra SK, et al. In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography. Br J Cancer. 2004;90(11):2232–42.Google Scholar
  159. 159.
    van Loon J, Janssen MH, Ollers M, Aerts HJ, Dubois L, Hochstenbag M, et al. PET imaging of hypoxia using [18F]HX4: a phase I trial. Eur J Nucl Med Mol Imaging. 2010;37(9):1663–8.Google Scholar
  160. 160.
    Dubois LJ, Lieuwes NG, Janssen MH, Peeters WJ, Windhorst AD, Walsh JC, et al. Preclinical evaluation and validation of [18F]HX4, a promising hypoxia marker for PET imaging. Proc Natl Acad Sci U S A. 2011;108(35):14620–5.Google Scholar
  161. 161.
    Tran LB, Bol A, Labar D, Jordan B, Magat J, Mignion L, et al. Hypoxia imaging with the nitroimidazole 18F-FAZA PET tracer: a comparison with OxyLite, EPR oximetry and 19F-MRI relaxometry. Radiother Oncol. 2012;105(1):29–35.Google Scholar
  162. 162.
    Valtorta S, Belloli S, Sanvito F, Masiello V, Di Grigoli G, Monterisi C, et al. Comparison of 18F-fluoroazomycin-arabinofuranoside and 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) in preclinical models of cancer. J Nucl Med. 2013;54(7):1106–12.Google Scholar
  163. 163.
    Doss M, Zhang JJ, Belanger MJ, Stubbs JB, Hostetler ED, Alpaugh K, et al. Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT. Nucl Med Commun. 2010;31(12):1016–24.Google Scholar
  164. 164.
    Hueting R, Kersemans V, Cornelissen B, Tredwell M, Hussien K, Christlieb M, et al. A comparison of the behavior of (64)Cu-acetate and (64)Cu-ATSM in vitro and in vivo. J Nucl Med. 2014;55(1):128–34.Google Scholar
  165. 165.
    Carlin S, Zhang H, Reese M, Ramos NN, Chen Q, Ricketts SA. A comparison of the imaging characteristics and microregional distribution of 4 hypoxia PET tracers. J Nucl Med. 2014;55(3):515–21.Google Scholar
  166. 166.
    Mees G, Dierckx R, Vangestel C, Van de Wiele C. Molecular imaging of hypoxia with radiolabelled agents. Eur J Nucl Med Mol Imaging. 2009;36(10):1674–86.Google Scholar
  167. 167.
    Honess DJ, Hill SA, Collingridge DR, Edwards B, Brauers G, Powell NA, et al. Preclinical evaluation of the novel hypoxic marker 99mTc-HL91 (Prognox) in murine and xenograft systems in vivo. Int J Radiat Oncol Biol Phys. 1998;42(4):731–5.Google Scholar
  168. 168.
    Li L, Yu JM, Sun XD, Zhu H, Yue JB, Sun CJ, et al. Prognostic value of 9mTc-HL91 SPECT hypoxia imaging in patients with advanced NSCLC. Zhonghua Zhong Liu Za Zhi. 2007;29(2):127–30.Google Scholar
  169. 169.
    Bensaad K, Tsuruta A, Selak MA, Vidal MNC, Nakano K, Bartrons R, et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell. 2006;126(1):107–20.Google Scholar
  170. 170.
    Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest. 2008;118(12):3930–42.Google Scholar
  171. 171.
    Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell. 2012;21(3):297–308.CrossRefPubMedCentralPubMedGoogle Scholar
  172. 172.
    Ploessl K, Wang L, Lieberman BP, Qu W, Kung HF. Comparative evaluation of 18Flabeled glutamic acid and glutamine as tumor metabolic imaging agents. J Nucl Med. 2012;53(10):1616–24.Google Scholar
  173. 173.
    Palaskas N, Larson SM, Schultz N, Komisopoulou E, Wong J, Rohle D, et al. 18Ffluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basallike breast cancers. Cancer Res. 2011;71(15):5164–74.Google Scholar
  174. 174.
    Contractor KB, Aboagye EO. Monitoring predominantly cytostatic treatment response with 18F-FDG PET. J Nucl Med. 2009;50 Suppl 1:97S–105.Google Scholar
  175. 175.
    Fletcher JW, Djulbegovic B, Soares HP, Siegel BA, Lowe VJ, Lyman GH, et al. Recommendations on the use of 18F-FDG PET in oncology. J Nucl Med. 2008;49(3):480–508.Google Scholar
  176. 176.
    Rousset M, Chevalier G, Rousset JP, Dussaulx E, Zweibaum A. Presence and cell growth-related variations of glycogen in human colorectal adenocarcinoma cell lines in culture. Cancer Res. 1979;39(2 Pt 1):531–4.Google Scholar
  177. 177.
    Takahashi S, Satomi A, Yano K, Kawase H, Tanimizu T, Tuji Y, et al. Estimation of glycogen levels in human colorectal cancer tissue: relationship with cell cycle and tumor outgrowth. J Gastroenterol. 1999;34(4):474–80.Google Scholar
  178. 178.
    Yamada S, Kubota K, Kubota R, Ido T, Tamahashi N. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med. 1995;36(7):1301–6.Google Scholar
  179. 179.
    Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11(2):85–95.CrossRefPubMedGoogle Scholar
  180. 180.
    Aboagye EO, Bhujwalla ZM. Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res. 1999;59(1):80–4.PubMedGoogle Scholar
  181. 181.
    Leyton J, Smith G, Zhao Y, Perumal M, Nguyen QD, Robins E, et al. [18F]fluoromethyl-[1,2-2H4]-choline: a novel radiotracer for imaging choline metabolism in tumors by positron emission tomography. Cancer Res. 2009;69(19):7721–8.Google Scholar
  182. 182.
    Nakagami K, Uchida T, Ohwada S, Koibuchi Y, Suda Y, Sekine T, et al. Increased choline kinase activity and elevated phosphocholine levels in human colon cancer. Jpn J Cancer Res. 1999;90(4):419–24.Google Scholar
  183. 183.
    Ramirez de Molina A, Sarmentero-Estrada J, Belda-Iniesta C, Taron M, Ramirez de Molina V, Cejas P, et al. Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer: a retrospective study. Lancet Oncol. 2007;8(10):889–97.Google Scholar
  184. 184.
    Jadvar H. Prostate cancer: PET with 18F-FDG, 18F- or 11C-acetate, and 18F- or 11C-choline. J Nucl Med. 2011;52(1):81–9.CrossRefPubMedCentralPubMedGoogle Scholar
  185. 185.
    Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, et al. Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol. 2003;169(4):1337–40.Google Scholar
  186. 186.
    Price DT, Coleman RE, Liao RP, Robertson CN, Polascik TJ, DeGrado TR. Comparison of [18F]fluorocholine and [18F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. J Urol. 2002;168(1):273–80.Google Scholar
  187. 187.
    DeGrado TR, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN, et al. Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. Cancer Res. 2001;61(1):110–7.Google Scholar
  188. 188.
    Beheshti M, Vali R, Langsteger W. [18F]fluorocholine PET/CT in the assessment of bone metastases in prostate cancer. Eur J Nucl Med Mol Imaging. 2007;34(8):1316–7. author reply 1318–9.Google Scholar
  189. 189.
    Scattoni V, Picchio M, Suardi N, Messa C, Freschi M, Roscigno M, et al. Detection of lymph-node metastases with integrated [11C]choline PET/CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur Urol. 2007;52(2):423–9.Google Scholar
  190. 190.
    Mitchell CR, Lowe VJ, Rangel LJ, Hung JC, Kwon ED, Karnes RJ. Operational characteristics of (11)c-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment. J Urol. 2013;189(4):1308–13.Google Scholar
  191. 191.
    Farsad M, Schiavina R, Castellucci P, Nanni C, Corti B, Martorana G, et al. Detection and localization of prostate cancer: correlation of (11)C-choline PET/CT with histopathologic stepsection analysis. J Nucl Med. 2005;46(10):1642–9.Google Scholar
  192. 192.
    Smith G, Zhao Y, Leyton J, Shan B, Nguyen QD, Perumal M, et al. Radiosynthesis and pre-clinical evaluation of [(18)F]fluoro-[1,2-(2)H(4)]choline. Nucl Med Biol. 2011;38(1):39–51.Google Scholar
  193. 193.
    Witney TH, Alam IS, Turton DR, Smith G, Carroll L, Brickute D, et al. Evaluation of deuterated 18F- and 11C-labeled choline analogs for cancer detection by positron emission tomography. Clin Cancer Res. 2012;18(4):1063–72.Google Scholar
  194. 194.
    Yoshii Y, Furukawa T, Oyama N, Hasegawa Y, Kiyono Y, Nishii R, et al. Fatty acid synthase is a key target in multiple essential tumor functions of prostate cancer: uptake of radiolabeled acetate as a predictor of the targeted therapy outcome. PLoS One. 2013;8(5):e64570.Google Scholar
  195. 195.
    Lewis DY, Boren J, Shaw GL, Bielik R, Ramos-Montoya A, Larkin TJ, et al. Late Imaging with [1-11C]Acetate Improves Detection of Tumor Fatty Acid Synthesis with PET. J Nucl Med. 2014;55(7):1144–9.Google Scholar
  196. 196.
    Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, et al. 11C-acetate PET imaging of prostate cancer. J Nucl Med. 2002;43(2):181–6.Google Scholar
  197. 197.
    Jambor I, Borra R, Kemppainen J, Lepomaki V, Parkkola R, Dean K, et al. Functional imaging of localized prostate cancer aggressiveness using 11C-acetate PET/CT and 1H-MR spectroscopy. J Nucl Med. 2010;51(11):1676–83.Google Scholar
  198. 198.
    Wang HC, Zhao J, Zuo CT, Zhang ZW, Xue FP, Liu P, et al. Encephalitis depicted by a combination of C-11 acetate and F-18 FDG PET/CT. Clin Nucl Med. 2009;34(12):952–4.Google Scholar
  199. 199.
    Grassi I, Nanni C, Allegri V, Morigi JJ, Montini GC, Castellucci P, et al. The clinical use of PET with (11)C-acetate. Am J Nucl Med Mol Imaging. 2012;2(1):33–47.Google Scholar
  200. 200.
    Ponde DE, Dence CS, Oyama N, Kim J, Tai YC, Laforest R, et al. 18F-fluoroacetate: a potential acetate analog for prostate tumor imaging–in vivo evaluation of 18F-fluoroacetate versus 11C-acetate. J Nucl Med. 2007;48(3):420–8.Google Scholar
  201. 201.
    Lindhe O, Sun A, Ulin J, Rahman O, Langstrom B, Sorensen J. [(18)F]Fluoroacetate is not a functional analogue of [(11)C]acetate in normal physiology. Eur J Nucl Med Mol Imaging. 2009;36(9):1453–9.Google Scholar
  202. 202.
    Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer. 2013;13(4):227–32.Google Scholar
  203. 203.
    Pisaneschi F, Witney T, Iddon L, Aboagye EO. Synthesis of [F-18]fluoropivalic acid: an improved PET imaging probe for the fatty acid synthesis pathway in tumours. Med Chem Comm. 2013;4:1350–3.Google Scholar
  204. 204.
    Witney TH, Pisaneschi F, Alam IS, Trousil S, Kaliszczak M, Twyman F, et al. Preclinical evaluation of 3-18F-fluoro-2,2-dimethylpropionic acid as an imaging agent for tumor detection. J Nucl Med. 2014;55(9):1506–12.Google Scholar
  205. 205.
    Gillies RJ, Raghunand N, Garcia-Martin ML, Gatenby RA. pH imaging. A review of pH measurement methods and applications in cancers. IEEE Eng Med Biol Mag. 2004;23(5):57–64.Google Scholar
  206. 206.
    Rottenberg DA, Ginos JZ, Kearfott KJ, Junck L, Dhawan V, Jarden JO. In vivo measurement of brain tumor pH using [11C]DMO and positron emission tomography. Ann Neurol. 1985;17(1):70–9.Google Scholar
  207. 207.
    Viola-Villegas NT, Carlin SD, Ackerstaff E, Sevak KK, Divilov V, Serganova I, et al. Understanding the pharmacological properties of a metabolic PET tracer in prostate cancer. Proc Natl Acad Sci U S A. 2014;111(20):7254–9.Google Scholar
  208. 208.
    Vavere AL, Biddlecombe GB, Spees WM, Garbow JR, Wijesinghe D, Andreev OA, et al. A novel technology for the imaging of acidic prostate tumors by positron emission tomography. Cancer Res. 2009;69(10):4510–6.Google Scholar
  209. 209.
    Nelson BH. The impact of T-cell immunity on ovarian cancer outcomes. Immunol Rev. 2008;222:101–16.CrossRefPubMedGoogle Scholar
  210. 210.
    Ferrone C, Dranoff G. Dual roles for immunity in gastrointestinal cancers. J Clin Oncol. 2010;28(26):4045–51.CrossRefPubMedGoogle Scholar
  211. 211.
    Mlecnik B, Tosolini M, Charoentong P, Kirilovsky A, Bindea G, Berger A, et al. Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology. 2010;138(4):1429–40.Google Scholar
  212. 212.
    Radu CG, Shu CJ, Nair-Gill E, Shelly SM, Barrio JR, Satyamurthy N, et al. Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog. Nat Med. 2008;14(7):783–8.Google Scholar
  213. 213.
    Nair-Gill E, Wiltzius SM, Wei XX, Cheng D, Riedinger M, Radu CG, et al. PET probes for distinct metabolic pathways have different cell specificities during immune responses in mice. J Clin Invest. 2010;120(6):2005–15.Google Scholar
  214. 214.
    Shu CJ, Campbell DO, Lee JT, Tran AQ, Wengrod JC, Witte ON, et al. Novel PET probes specific for deoxycytidine kinase. J Nucl Med. 2010;51(7):1092–8.Google Scholar
  215. 215.
    Murphy JM, Armijo AL, Nomme J, Lee CH, Smith QA, Li Z, et al. Development of new deoxycytidine kinase inhibitors and noninvasive in vivo evaluation using positron emission tomography. J Med Chem. 2013;56(17):6696–708.Google Scholar
  216. 216.
    Zeppernick F, Ahmadi R, Campos B, Dictus C, Helmke BM, Becker N, et al. Stem cell marker CD133 affects clinical outcome in glioma patients. Clin Cancer Res. 2008;14(1):123–9.Google Scholar
  217. 217.
    Holland JP, Evans MJ, Rice SL, Wongvipat J, Sawyers CL, Lewis JS. Annotating MYC status with 89Zr-transferrin imaging. Nat Med. 2012;18(10):1586–91.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Israt S. Alam
    • 1
  • Mubarik A. Arshad
    • 1
  • Quang-Dé Nguyen
    • 1
  • Eric O. Aboagye
    • 1
    Email author
  1. 1.Comprehensive Cancer Imaging CentreImperial College LondonLondonUK

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