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PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies

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Abstract

We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [11C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging.

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References

  1. Hara T, Kosaka N, Shinoura N, Kondo T. PET imaging of brain tumor with [methyl-11C]choline. J Nucl Med. 1997;38:842–7.

    CAS  PubMed  Google Scholar 

  2. Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Hammer J, et al. The use of F-18 choline PET in the assessment of bone metastases in prostate cancer: correlation with morphological changes on CT. Mol Imaging Biol. 2009;11:446–54.

    Article  PubMed  Google Scholar 

  3. Shinoura N, Nishijima M, Hara T, Haisa T, Yamamoto H, Fujii K, et al. Brain tumors: detection with C-11 choline PET. Radiology. 1997;202:497–503.

    Article  CAS  PubMed  Google Scholar 

  4. Shimizu H, Kumabe T, Tominaga T, Kayama T, Hara K, Ono Y, et al. Noninvasive evaluation of malignancy of brain tumors with proton MR spectroscopy. AJNR Am J Neuroradiol. 1996;17:737–47.

    CAS  PubMed  Google Scholar 

  5. Yavin E. Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture: ontogenesis of carrier-specific transport of choline and N-methyl-substituted choline analogs. J Neurochem. 1980;34:178–83.

    Article  CAS  PubMed  Google Scholar 

  6. Lanks K, Somers L, Papirmeister B, Yamamura H. Choline transport by neuroblastoma cells in tissue culture. Nature. 1974;252:476–8.

    Article  CAS  PubMed  Google Scholar 

  7. George TP, Morash SC, Cook HW, Byers DM, Palmer FB, Spence MW. Phosphatidylcholine biosynthesis in cultured glioma cells: evidence for channeling of intermediates. Biochim Biophys Acta. 1989;1004:283–91.

    Article  CAS  PubMed  Google Scholar 

  8. Ramirez de Molina A, Rodriguez-Gonzalez A, Gutierrez R, Martinez-Pineiro L, Sanchez J, Bonilla F, et al. Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun. 2002;296:580–3.

    Article  CAS  PubMed  Google Scholar 

  9. Ackerstaff E, Pflug BR, Nelson JB, Bhujwalla ZM. Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells. Cancer Res. 2001;61:3599–603.

    CAS  PubMed  Google Scholar 

  10. Heerschap A, Jager GJ, van der Graaf M, Barentsz JO, de la Rosette JJ, Oosterhof GO, et al. In vivo proton MR spectroscopy reveals altered metabolite content in malignant prostate tissue. Anticancer Res. 1997;17:1455–60.

    CAS  PubMed  Google Scholar 

  11. Friedland RP, Mathis CA, Budinger TF, Moyer BR, Rosen M. Labeled choline and phosphorylcholine: body distribution and brain autoradiography: concise communication. J Nucl Med. 1983;24:812–5.

    CAS  PubMed  Google Scholar 

  12. 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;61:110–7.

    CAS  PubMed  Google Scholar 

  13. Hara T, Kosaka N, Kishi H. Development of (18)F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med. 2002;43:187–99.

    CAS  PubMed  Google Scholar 

  14. Tian M, Zhang H, Oriuchi N, Higuchi T, Endo K. Comparison of 11C-choline PET and FDG PET for the differential diagnosis of malignant tumors. Eur J Nucl Med Mol Imaging. 2004;31:1064–72.

    CAS  PubMed  Google Scholar 

  15. Utriainen M, Komu M, Vuorinen V, Lehikoinen P, Sonninen P, Kurki T, et al. Evaluation of brain tumor metabolism with [11C]choline PET and 1H-MRS. J Neuro-Oncol. 2003;62:329–38.

    Article  CAS  Google Scholar 

  16. Fallanca F, Giovacchini G, Picchio M, Bettinardi V, Messa C, Fazio F. Incidental detection by [11C]choline PET/CT of meningiomas in prostate cancer patients. Q J Nucl Med Mol Imaging. 2009;53:417–21.

    CAS  PubMed  Google Scholar 

  17. Giovacchini G, Fallanca F, Landoni C, Gianolli L, Picozzi P, Attuati L, et al. C-11 choline versus F-18 fluorodeoxyglucose for imaging meningiomas: an initial experience. Clin Nucl Med. 2009;34:7–10.

    Article  PubMed  Google Scholar 

  18. Giovannini E, Lazzeri P, Milano A, Gaeta MC, Ciarmiello A. Clinical applications of choline PET/CT in brain tumors. Curr Pharm Des. 2015;21:121–7.

    Article  CAS  PubMed  Google Scholar 

  19. Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med. 1998;39:990–5.

    CAS  PubMed  Google Scholar 

  20. Seltzer MA, Barbaric Z, Belldegrun A, Naitoh J, Dorey F, Phelps ME, et al. Comparison of helical computerized tomography, positron emission tomography and monoclonal antibody scans for evaluation of lymph node metastases in patients with prostate specific antigen relapse after treatment for localized prostate cancer. J Urol. 1999;162:1322–8.

    Article  CAS  PubMed  Google Scholar 

  21. Tiguert R, Gheiler EL, Tefilli MV, Oskanian P, Banerjee M, Grignon DJ, et al. Lymph node size does not correlate with the presence of prostate cancer metastasis. Urology. 1999;53:367–71.

    Article  CAS  PubMed  Google Scholar 

  22. Cher ML, Bianco Jr FJ, Lam JS, Davis LP, Grignon DJ, Sakr WA, et al. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol. 1998;160:1387–91.

    Article  CAS  PubMed  Google Scholar 

  23. Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS, Thrasher JB, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology. 2003;61:607–11.

    Article  PubMed  Google Scholar 

  24. Dotan ZA, Bianco Jr FJ, Rabbani F, Eastham JA, Fearn P, Scher HI, et al. Pattern of prostate-specific antigen (PSA) failure dictates the probability of a positive bone scan in patients with an increasing PSA after radical prostatectomy. J Clin Oncol. 2005;23:1962–8.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Even-Sapir E, Flusser G, Lerman H, Lievshitz G, Metser U. SPECT/multislice low-dose CT: a clinically relevant constituent in the imaging algorithm of nononcologic patients referred for bone scintigraphy. J Nucl Med. 2007;48:319–24.

    PubMed  Google Scholar 

  26. Beheshti M, Langsteger W, Fogelman I. Prostate cancer: role of SPECT and PET in imaging bone metastases. Semin Nucl Med. 2009;39:396–407.

    Article  PubMed  Google Scholar 

  27. Hofer C, Laubenbacher C, Block T, Breul J, Hartung R, Schwaiger M. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. Eur Urol. 1999;36:31–5.

    Article  CAS  PubMed  Google Scholar 

  28. Salminen E, Hogg A, Binns D, Frydenberg M, Hicks R. Investigations with FDG-PET scanning in prostate cancer show limited value for clinical practice. Acta Oncol. 2002;41:425–9.

    Article  PubMed  Google Scholar 

  29. Yeh SD, Imbriaco M, Larson SM, Garza D, Zhang JJ, Kalaigian H, et al. Detection of bony metastases of androgen-independent prostate cancer by PET-FDG. Nucl Med Biol. 1996;23:693–7.

    Article  CAS  PubMed  Google Scholar 

  30. Muller SA, Holzapfel K, Seidl C, Treiber U, Krause BJ, Senekowitsch-Schmidtke R. Characterization of choline uptake in prostate cancer cells following bicalutamide and docetaxel treatment. Eur J Nucl Med Mol Imaging. 2009;36:1434–42.

    Article  PubMed  CAS  Google Scholar 

  31. Al-Saeedi F, Smith T, Welch A. [methyl-3H]-choline incorporation into MCF-7 cells: correlation with proliferation, choline kinase and phospholipase D assay. Anticancer Res. 2007;27:901–6.

    CAS  PubMed  Google Scholar 

  32. Al-Saeedi F, Welch AE, Smith TA. [methyl-3H]choline incorporation into MCF7 tumour cells: correlation with proliferation. Eur J Nucl Med Mol Imaging. 2005;32:660–7.

    Article  CAS  PubMed  Google Scholar 

  33. Yoshimoto M, Waki A, Obata A, Furukawa T, Yonekura Y, Fujibayashi Y. Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate. Nucl Med Biol. 2004;31:859–65.

    Article  CAS  PubMed  Google Scholar 

  34. Breeuwsma AJ, Pruim J, Jongen MM, Suurmeijer AJ, Vaalburg W, Nijman RJ, et al. In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer. Eur J Nucl Med Mol Imaging. 2005;32:668–73.

    Article  PubMed  Google Scholar 

  35. Briganti A, Giannarini G, Karnes RJ, Gandaglia G, Ficarra V, Montorsi F. What evidence do we need to support the use of extended pelvic lymph node dissection in prostate cancer? Eur Urol. 2015;67:597–8.

    Article  PubMed  Google Scholar 

  36. Heidenreich A, Varga Z, Von Knobloch R. Extended pelvic lymphadenectomy in patients undergoing radical prostatectomy: high incidence of lymph node metastasis. J Urol. 2002;167:1681–6.

    Article  PubMed  Google Scholar 

  37. Hinev AI, Hadjiev VI, Kolev NH. Validation of preoperative nomograms predicting lymph node involvement in prostate cancer: a bi-institutional study. Eur Urol. 2011;60:1310–1.

    Article  PubMed  Google Scholar 

  38. Mitsuzuka K, Koie T, Narita S, Kaiho Y, Yoneyama T, Kawamura S, et al. Is pelvic lymph node dissection required at radical prostatectomy for low-risk prostate cancer? Int J Urol. 2013;20:1092–6.

    Article  PubMed  Google Scholar 

  39. Meijer HJ, Debats OA, Th van Lin EN, van Vulpen M, Witjes JA, Oyen WJ, et al. Individualized image-based lymph node irradiation for prostate cancer. Nat Rev Urol. 2013;10:376–85.

    Article  CAS  PubMed  Google Scholar 

  40. Evangelista L, Guttilla A, Zattoni F, Muzzio PC. Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis. Eur Urol. 2013;63:1040–8.

    Article  PubMed  Google Scholar 

  41. Poulsen MH, Bouchelouche K, Gerke O, Petersen H, Svolgaard B, Marcussen N, et al. [18F]-fluorocholine positron-emission/computed tomography for lymph node staging of patients with prostate cancer: preliminary results of a prospective study. BJU Int. 2010;106:639–43.

    Article  PubMed  Google Scholar 

  42. Poulsen MH, Bouchelouche K, Hoilund-Carlsen PF, Petersen H, Gerke O, Steffansen SI, 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;110:1666–71.

    Article  CAS  PubMed  Google Scholar 

  43. Schiavina R, Scattoni V, Castellucci P, Picchio M, Corti B, Briganti A, et al. 11C-choline positron emission tomography/computerized tomography for preoperative lymph-node staging in intermediate-risk and high-risk prostate cancer: comparison with clinical staging nomograms. Eur Urol. 2008;54:392–401.

    Article  PubMed  Google Scholar 

  44. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Preoperative staging of pelvic lymph nodes in prostate cancer by 11C-choline PET. J Nucl Med. 2003;44:331–5.

    PubMed  Google Scholar 

  45. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Visualization of prostate cancer with 11C-choline positron emission tomography. Eur Urol. 2002;42:18–23.

    Article  PubMed  Google Scholar 

  46. Steuber T, Schlomm T, Heinzer H, Zacharias M, Ahyai S, Chun KF, et al. [F(18)]-fluoroethylcholine combined in-line PET-CT scan for detection of lymph-node metastasis in high risk prostate cancer patients prior to radical prostatectomy: preliminary results from a prospective histology-based study. Eur J Cancer. 2010;46:449–55.

    Article  CAS  PubMed  Google Scholar 

  47. Schmid DT, John H, Zweifel R, Cservenyak T, Westera G, Goerres GW, et al. Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology. 2005;235:623–8.

    Article  PubMed  Google Scholar 

  48. Scher B, Seitz M, Albinger W, Tiling R, Scherr M, Becker HC, et al. Value of 11C-choline PET and PET/CT in patients with suspected prostate cancer. Eur J Nucl Med Mol Imaging. 2007;34:45–53.

    Article  PubMed  Google Scholar 

  49. Budiharto T, Joniau S, Lerut E, Van den Bergh L, Mottaghy F, Deroose CM, et al. Prospective evaluation of 11C-choline positron emission tomography/computed tomography and diffusion-weighted magnetic resonance imaging for the nodal staging of prostate cancer with a high risk of lymph node metastases. Eur Urol. 2011;60:125–30.

    Article  PubMed  Google Scholar 

  50. Hacker A, Jeschke S, Leeb K, Prammer K, Ziegerhofer J, Sega W, et al. Detection of pelvic lymph node metastases in patients with clinically localized prostate cancer: comparison of [18F]fluorocholine positron emission tomography-computerized tomography and laparoscopic radioisotope guided sentinel lymph node dissection. J Urol. 2006;176:2014–8.

    Article  PubMed  Google Scholar 

  51. Husarik DB, Miralbell R, Dubs M, John H, Giger OT, Gelet A, et al. Evaluation of [(18)F]-choline PET/CT for staging and restaging of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:253–63.

    Article  PubMed  Google Scholar 

  52. Oppenheimer DC, Weinberg EP, Hollenberg GM, Meyers SP. Multiparametric magnetic resonance imaging of recurrent prostate cancer. J Clin Imaging Sci. 2016;6:18.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kattan MW, Yu C, Stephenson AJ, Sartor O, Tombal B. Clinicians versus nomogram: predicting future technetium-99m bone scan positivity in patients with rising prostate-specific antigen after radical prostatectomy for prostate cancer. Urology. 2013;81:956–61.

    Article  PubMed  Google Scholar 

  54. Dotan ZA. Bone imaging in prostate cancer. Nat Clin Pract Urol. 2008;5:434–44.

    Article  PubMed  Google Scholar 

  55. Langsteger W, Haim S, Knauer M, Waldenberger P, Emmanuel K, Loidl W, et al. Imaging of bone metastases in prostate cancer: an update. Q J Nucl Med Mol Imaging. 2012;56:447–58.

    CAS  PubMed  Google Scholar 

  56. Vali R, Loidl W, Pirich C, Langesteger W, Beheshti M. Imaging of prostate cancer with PET/CT using (18)F-Fluorocholine. Am J Nucl Med Mol Imaging. 2015;5:96–108.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Beauregard JM, Williams SG, Degrado TR, Roselt P, Hicks RJ. Pilot comparison of F-fluorocholine and F-fluorodeoxyglucose PET/CT with conventional imaging in prostate cancer. J Med Imaging Radiat Oncol. 2010;54:325–32.

    Article  PubMed  Google Scholar 

  58. Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Hammer J, et al. The use of F-18 choline PET in the assessment of bone metastases in prostate cancer: correlation with morphological changes on CT. Mol Imaging Biol. 2010;12:98–107.

    Article  PubMed  Google Scholar 

  59. Beheshti M, Imamovic L, Broinger G, Vali R, Waldenberger P, Stoiber F, et al. 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology. 2010;254:925–33.

    Article  PubMed  Google Scholar 

  60. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2005. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  61. Kotzerke J, Prang J, Neumaier B, Volkmer B, Guhlmann A, Kleinschmidt K, et al. Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur J Nucl Med. 2000;27:1415–9.

    Article  CAS  PubMed  Google Scholar 

  62. Hara T. 11C-choline and 2-deoxy-2-[18F]fluoro-D-glucose in tumor imaging with positron emission tomography. Mol Imaging Biol. 2002;4:267–73.

    Article  PubMed  Google Scholar 

  63. Picchio M, Briganti A, Fanti S, Heidenreich A, Krause BJ, Messa C, et al. The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer. Eur Urol. 2011;59:51–60.

    Article  PubMed  Google Scholar 

  64. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. 11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol. 2003;44:32–8.

    Article  PubMed  Google Scholar 

  65. Kotzerke J, Volkmer BG, Glatting G, van den Hoff J, Gschwend JE, Messer P, et al. Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer. Nuklearmedizin. 2003;42:25–30.

    CAS  PubMed  Google Scholar 

  66. Reske SN, Blumstein NM, Glatting G. [11C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2008;35:9–17.

    Article  PubMed  Google Scholar 

  67. 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;169:1337–40.

    Article  CAS  PubMed  Google Scholar 

  68. Ceci F, Herrmann K, Castellucci P, Graziani T, Bluemel C, Schiavina R, et al. Impact of 11C-choline PET/CT on clinical decision making in recurrent prostate cancer: results from a retrospective two-centre trial. Eur J Nucl Med Mol Imaging. 2014;41:2222–31.

    Article  PubMed  Google Scholar 

  69. Soyka JD, Muster MA, Schmid DT, Seifert B, Schick U, Miralbell R, et al. Clinical impact of 18F-choline PET/CT in patients with recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2012;39:936–43.

    Article  CAS  PubMed  Google Scholar 

  70. Giovacchini G, Incerti E, Mapelli P, Kirienko M, Briganti A, Gandaglia G, et al. [11C]choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2015;42:877–84.

    Article  CAS  PubMed  Google Scholar 

  71. Giovacchini G, Picchio M, Garcia-Parra R, Briganti A, Abdollah F, Gianolli L, et al. 11C-choline PET/CT predicts prostate cancer-specific survival in patients with biochemical failure during androgen-deprivation therapy. J Nucl Med. 2014;55:233–41.

    Article  CAS  PubMed  Google Scholar 

  72. Suardi N, Gandaglia G, Gallina A, Di Trapani E, Scattoni V, Vizziello D, et al. Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single-institution series with a minimum follow-up of 5 years. Eur Urol. 2015;67:299–309.

    Article  PubMed  Google Scholar 

  73. Kwee SA, Lim J, Watanabe A, Kromer-Baker K, Coel MN. Prognosis related to metastatic burden measured by (1)(8)F-Fluorocholine PET/CT in castration-resistant prostate cancer. J Nucl Med. 2014;55:905–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 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;168:273–80.

    Article  PubMed  Google Scholar 

  75. Jadvar H. FDG PET in prostate cancer. PET Clin. 2009;4:155–61.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico AV, Dmochowski RR, et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American urological association prostate guidelines for localized prostate cancer update panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol. 2007;177:540–5.

    Article  CAS  PubMed  Google Scholar 

  77. Roach 3rd M, Weinberg V, Nash M, Sandler HM, McLaughlin PW, Kattan MW. Defining high risk prostate cancer with risk groups and nomograms: implications for designing clinical trials. J Urol. 2006;176:S16–20.

    Article  PubMed  Google Scholar 

  78. 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;64:106–17.

    Article  PubMed  Google Scholar 

  79. Evangelista L, Zattoni F, Guttilla A, Saladini G, Colletti PM, Rubello D. Choline PET or PET/CT and biochemical relapse of prostate cancer: a systematic review and meta-analysis. Clin Nucl Med. 2013;38:305–14.

    Article  PubMed  Google Scholar 

  80. Evangelista L, Briganti A, Fanti S, Joniau S, Reske S, Schiavina R, et al. New clinical indications for (18)F/(11)C-choline, new tracers for positron emission tomography and a promising hybrid device for prostate cancer staging: a systematic review of the literature. Eur Urol. 2016;70:161–75.

    Article  PubMed  Google Scholar 

  81. Fanti S, Minozzi S, Castellucci P, Balduzzi S, Herrmann K, Krause BJ, et al. PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. 2016;43:55–69.

    Article  CAS  PubMed  Google Scholar 

  82. Krause BJ, Souvatzoglou M, Tuncel M, Herrmann K, Buck AK, Praus C, et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging. 2008;35:18–23.

    Article  CAS  PubMed  Google Scholar 

  83. Giovacchini G, Picchio M, Coradeschi E, Bettinardi V, Gianolli L, Scattoni V, et al. Predictive factors of [(11)C]choline PET/CT in patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2010;37:301–9.

    Article  PubMed  Google Scholar 

  84. Heinisch M, Dirisamer A, Loidl W, Stoiber F, Gruy B, Haim S, et al. Positron emission tomography/computed tomography with F-18-fluorocholine for restaging of prostate cancer patients: meaningful at PSA < 5 ng/ml? Mol Imaging Biol. 2006;8:43–8.

    Article  PubMed  Google Scholar 

  85. Giovacchini G, Picchio M, Briganti A, Cozzarini C, Scattoni V, Salonia A, et al. [11C]choline positron emission tomography/computerized tomography to restage prostate cancer cases with biochemical failure after radical prostatectomy and no disease evidence on conventional imaging. J Urol. 2010;184:938–43.

    Article  PubMed  Google Scholar 

  86. Detti B, Scoccianti S, Franceschini D, Cipressi S, Cassani S, Villari D, et al. Predictive factors of [18F]-choline PET/CT in 170 patients with increasing PSA after primary radical treatment. J Cancer Res Clin Oncol. 2013;139:521–8.

    Article  CAS  PubMed  Google Scholar 

  87. Steiner C, Vees H, Zaidi H, Wissmeyer M, Berrebi O, Kossovsky MP, et al. Three-phase 18F-fluorocholine PET/CT in the evaluation of prostate cancer recurrence. Nuklearmedizin. 2009;48:1–9.

    PubMed  Google Scholar 

  88. Beheshti M, Haim S, Zakavi R, Steinmair M, Waldenberger P, Kunit T, et al. Impact of 18F-choline PET/CT in prostate cancer patients with biochemical recurrence: influence of androgen deprivation therapy and correlation with PSA kinetics. J Nucl Med. 2013;54:833–40.

    Article  CAS  PubMed  Google Scholar 

  89. Marzola MC, Chondrogiannis S, Ferretti A, Grassetto G, Rampin L, Massaro A, et al. Role of 18F-choline PET/CT in biochemically relapsed prostate cancer after radical prostatectomy: correlation with trigger PSA, PSA velocity, PSA doubling time, and metastatic distribution. Clin Nucl Med. 2013;38:e26–32.

    Article  PubMed  Google Scholar 

  90. Graute V, Jansen N, Ubleis C, Seitz M, Hartenbach M, Scherr MK, et al. Relationship between PSA kinetics and [18F]fluorocholine PET/CT detection rates of recurrence in patients with prostate cancer after total prostatectomy. Eur J Nucl Med Mol Imaging. 2012;39:271–82.

    Article  CAS  PubMed  Google Scholar 

  91. Castellucci P, Fuccio C, Rubello D, Schiavina R, Santi I, Nanni C, et al. Is there a role for (11)C-choline PET/CT in the early detection of metastatic disease in surgically treated prostate cancer patients with a mild PSA increase <1.5 ng/ml? Eur J Nucl Med Mol Imaging. 2011;38:55–63.

    Article  PubMed  Google Scholar 

  92. Giovacchini G, Picchio M, Garcia-Parra R, Mapelli P, Briganti A, Montorsi F, et al. [11C]choline positron emission tomography/computerized tomography for early detection of prostate cancer recurrence in patients with low increasing prostate specific antigen. J Urol. 2013;189:105–10.

    Article  PubMed  Google Scholar 

  93. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014;65:124–37.

    Article  PubMed  Google Scholar 

  94. Graziani T, Ceci F, Castellucci P, Polverari G, Lima GM, Lodi F, et al. (11)C-choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series. Eur J Nucl Med Mol Imaging. 2016;43:1971–9.

    Article  CAS  PubMed  Google Scholar 

  95. Giovacchini G, Picchio M, Scattoni V, Garcia Parra R, Briganti A, Gianolli L, et al. PSA doubling time for prediction of [(11)C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2010;37:1106–16.

    Article  CAS  PubMed  Google Scholar 

  96. Castellucci P, Fuccio C, Nanni C, Santi I, Rizzello A, Lodi F, et al. Influence of trigger PSA and PSA kinetics on 11C-choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy. J Nucl Med. 2009;50:1394–400.

    Article  PubMed  CAS  Google Scholar 

  97. Suardi N, Briganti A, Salonia A, Rigatti P. Salvage lymphadenectomy in postprostatectomy patients with prostate-specific antigen recurrence. Curr Opin Urol. 2011;21:237–40.

    Article  PubMed  Google Scholar 

  98. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71:630–42.

    Article  PubMed  Google Scholar 

  99. Partin AW, Pearson JD, Landis PK, Carter HB, Pound CR, Clemens JQ, et al. Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. Urology. 1994;43:649–59.

    Article  CAS  PubMed  Google Scholar 

  100. Giovacchini G, Picchio M, Parra RG, Briganti A, Gianolli L, Montorsi F, et al. Prostate-specific antigen velocity versus prostate-specific antigen doubling time for prediction of 11C choline PET/CT in prostate cancer patients with biochemical failure after radical prostatectomy. Clin Nucl Med. 2012;37:325–31.

    Article  PubMed  Google Scholar 

  101. Schillaci O, Calabria F, Tavolozza M, Caracciolo CR, Finazzi Agro E, Miano R, et al. Influence of PSA, PSA velocity and PSA doubling time on contrast-enhanced 18F-choline PET/CT detection rate in patients with rising PSA after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2012;39:589–96.

    Article  CAS  PubMed  Google Scholar 

  102. Treglia G, Ceriani L, Sadeghi R, Giovacchini G, Giovanella L. Relationship between prostate-specific antigen kinetics and detection rate of radiolabelled choline PET/CT in restaging prostate cancer patients: a meta-analysis. Clin Chem Lab Med. 2014;52:725–33.

    Article  CAS  PubMed  Google Scholar 

  103. Ceci F, Castellucci P, Mamede M, Schiavina R, Rubello D, Fuccio C, et al. (11)C-choline PET/CT in patients with hormone-resistant prostate cancer showing biochemical relapse after radical prostatectomy. Eur J Nucl Med Mol Imaging. 2013;40:149–55.

    Article  CAS  PubMed  Google Scholar 

  104. Tan H, Joseph D, Loh NK, McCarthy M, Leong E, Siew T, et al. A pilot study of the utility of choline PET-CT in prostate cancer biochemical relapse following radical prostatectomy. J Med Imaging Radiat Oncol. 2016;60:374–81.

    Article  PubMed  Google Scholar 

  105. Castellucci P, Ceci F, Graziani T, Schiavina R, Brunocilla E, Mazzarotto R, et al. Early biochemical relapse after radical prostatectomy: which prostate cancer patients may benefit from a restaging 11C-choline PET/CT scan before salvage radiation therapy? J Nucl Med. 2014;55:1424–9.

    Article  CAS  PubMed  Google Scholar 

  106. Cimitan M, Evangelista L, Hodolic M, Mariani G, Baseric T, Bodanza V, et al. Gleason score at diagnosis predicts the rate of detection of 18F-choline PET/CT performed when biochemical evidence indicates recurrence of prostate cancer: experience with 1,000 patients. J Nucl Med. 2015;56:209–15.

    Article  PubMed  CAS  Google Scholar 

  107. Epstein JI, Walsh PC, Carter HB. Dedifferentiation of prostate cancer grade with time in men followed expectantly for stage T1c disease. J Urol. 2001;166:1688–91.

    Article  CAS  PubMed  Google Scholar 

  108. Falchook AD, Martin NE, Basak R, Smith AB, Milowsky MI, Chen RC. Stage at presentation and survival outcomes of patients with Gleason 8-10 prostate cancer and low prostate-specific antigen. Urol Oncol. 2016;34:119.e19–26.

    Article  Google Scholar 

  109. Alenda O, Ploussard G, Mouracade P, Xylinas E, de la Taille A, Allory Y, et al. Impact of the primary Gleason pattern on biochemical recurrence-free survival after radical prostatectomy: a single-center cohort of 1,248 patients with Gleason 7 tumors. World J Urol. 2011;29:671–6.

    Article  CAS  PubMed  Google Scholar 

  110. Sakr WA, Tefilli MV, Grignon DJ, Banerjee M, Dey J, Gheiler EL, et al. Gleason score 7 prostate cancer: a heterogeneous entity? Correlation with pathologic parameters and disease-free survival. Urology. 2000;56:730–4.

    Article  CAS  PubMed  Google Scholar 

  111. Tollefson MK, Leibovich BC, Slezak JM, Zincke H, Blute ML. Long-term prognostic significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer: impact on prostate cancer specific survival. J Urol. 2006;175:547–51.

    Article  PubMed  Google Scholar 

  112. Boccon-Gibod L. Global update on defining and treating high-risk localized prostate cancer with leuprorelin: a European perspective. BJU Int. 2007;99(Suppl 1):2–5.

    Article  CAS  PubMed  Google Scholar 

  113. Vees H, Buchegger F, Albrecht S, Khan H, Husarik D, Zaidi H, et al. 18F-choline and/or 11C-acetate positron emission tomography: detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/mL) after radical prostatectomy. BJU Int. 2007;99:1415–20.

    Article  CAS  PubMed  Google Scholar 

  114. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the prostate cancer clinical trials working group. J Clin Oncol. 2008;26:1148–59.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Mueller-Lisse UG, Swanson MG, Vigneron DB, Hricak H, Bessette A, Males RG, et al. Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging. Magn Reson Med. 2001;46:49–57.

    Article  CAS  PubMed  Google Scholar 

  116. Swinnen JV, Esquenet M, Goossens K, Heyns W, Verhoeven G. Androgens stimulate fatty acid synthase in the human prostate cancer cell line LNCaP. Cancer Res. 1997;57:1086–90.

    CAS  PubMed  Google Scholar 

  117. De Waele A, Van Binnebeek S, Mottaghy FM. Response assessment of hormonal therapy in prostate cancer by [11C] choline PET/CT. Clin Nucl Med. 2010;35:701–3.

    Article  PubMed  Google Scholar 

  118. Giovacchini G, Picchio M, Coradeschi E, Scattoni V, Bettinardi V, Cozzarini C, et al. [11C]choline uptake with PET/CT for the initial diagnosis of prostate cancer: relation to PSA levels, tumour stage and anti-androgenic therapy. Eur J Nucl Med Mol Imaging. 2008;35:1065–73.

    Article  CAS  PubMed  Google Scholar 

  119. Evangelista L, Zattoni F, Guttilla A, Basso U, Zattoni F. The effects of androgen deprivation therapy on the 18F–choline uptake in prostate cancer patients undergoing neoadjuvant treatment. Q J Nucl Med Mol Imaging. 2016. (in press).

  120. Giovacchini G. Do we have to withdraw antiandrogenic therapy in prostate cancer patients before PET/CT with [11C]choline? Eur J Nucl Med Mol Imaging. 2011;38:1964–6.

    Article  PubMed  Google Scholar 

  121. Nakashima J, Imai Y, Tachibana M, Baba S, Hiramatsu K, Murai M. Effects of endocrine therapy on the primary lesion in patients with prostate carcinoma as evaluated by endorectal magnetic resonance imaging. Cancer. 1997;80:237–41.

    Article  CAS  PubMed  Google Scholar 

  122. Swinnen JV, Verhoeven G. Androgens and the control of lipid metabolism in human prostate cancer cells. J Steroid Biochem Mol Biol. 1998;65:191–8.

    Article  CAS  PubMed  Google Scholar 

  123. Agus DB, Golde DW, Sgouros G, Ballangrud A, Cordon-Cardo C, Scher HI. Positron emission tomography of a human prostate cancer xenograft: association of changes in deoxyglucose accumulation with other measures of outcome following androgen withdrawal. Cancer Res. 1998;58:3009–14.

    CAS  PubMed  Google Scholar 

  124. Richter JA, Rodriguez M, Rioja J, Penuelas I, Marti-Climent J, Garrastachu P, et al. Dual tracer 11C-choline and FDG-PET in the diagnosis of biochemical prostate cancer relapse after radical treatment. Mol Imaging Biol. 2010;12:210–7.

    Article  PubMed  Google Scholar 

  125. Chondrogiannis S, Marzola MC, Ferretti A, Grassetto G, Maffione AM, Rampin L, et al. Is the detection rate of 18F-choline PET/CT influenced by androgen-deprivation therapy? Eur J Nucl Med Mol Imaging. 2014;41:1293–300.

    Article  CAS  PubMed  Google Scholar 

  126. Fuccio C, Schiavina R, Castellucci P, Rubello D, Martorana G, Celli M, et al. Androgen deprivation therapy influences the uptake of 11C-choline in patients with recurrent prostate cancer: the preliminary results of a sequential PET/CT study. Eur J Nucl Med Mol Imaging. 2011;38:1985–9.

    Article  CAS  PubMed  Google Scholar 

  127. Dost RJ, Glaudemans AW, Breeuwsma AJ, de Jong IJ. Influence of androgen deprivation therapy on choline PET/CT in recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40(Suppl 1):41–7.

    Article  CAS  Google Scholar 

  128. van Waarde A, Jager PL, Ishiwata K, Dierckx RA, Elsinga PH. Comparison of sigma-ligands and metabolic PET tracers for differentiating tumor from inflammation. J Nucl Med. 2006;47:150–4.

    PubMed  Google Scholar 

  129. 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;52:423–9.

    Article  PubMed  Google Scholar 

  130. Rinnab L, Mottaghy FM, Simon J, Volkmer BG, de Petriconi R, Hautmann RE, et al. [11C]choline PET/CT for targeted salvage lymph node dissection in patients with biochemical recurrence after primary curative therapy for prostate cancer. Preliminary results of a prospective study. Urol Int. 2008;81:191–7.

    Article  PubMed  Google Scholar 

  131. Giovacchini G, Gajate AM, Messa C, Fazio F. Increased C-11 choline uptake in pagetic bone in a patient with coexisting skeletal metastases from prostate cancer. Clin Nucl Med. 2008;33:797–8.

    Article  PubMed  Google Scholar 

  132. Bertagna F, Abuhilal M, Bosio G, Simeone C, Rossini P, Pizzocaro C, et al. Role of (1)(1)C-choline positron emission tomography/computed tomography in evaluating patients affected by prostate cancer with suspected relapse due to prostate-specific antigen elevation. Jpn J Radiol. 2011;29:394–404.

    Article  CAS  PubMed  Google Scholar 

  133. McCarthy M, Siew T, Campbell A, Lenzo N, Spry N, Vivian J, et al. (18)F-Fluoromethylcholine (FCH) PET imaging in patients with castration-resistant prostate cancer: prospective comparison with standard imaging. Eur J Nucl Med Mol Imaging. 2011;38:14–22.

    Article  PubMed  Google Scholar 

  134. Fanti S, Lalumera E. Of standard of reference and accuracy: the problem of truth in imaging. Eur J Nucl Med Mol Imaging. 2016;43:52–4.

    Article  PubMed  Google Scholar 

  135. von Eyben FE, Kairemo K. Meta-analysis of (11)C-choline and (18)F-choline PET/CT for management of patients with prostate cancer. Nucl Med Commun. 2014;35:221–30.

    Article  CAS  Google Scholar 

  136. Caffo O, Maines F, Donner D, Veccia A, Chierichetti F, Galligioni E. Impact of enzalutamide administration on primary prostate cancer volume: a metabolic evaluation by choline positron emission tomography in castration-resistant prostate cancer patients. Clin Genitourin Cancer. 2014;12:312–6.

    Article  PubMed  Google Scholar 

  137. De Giorgi U, Caroli P, Burgio SL, Menna C, Conteduca V, Bianchi E, et al. Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone. Oncotarget. 2014;5:12448–58.

    Article  PubMed  PubMed Central  Google Scholar 

  138. De Giorgi U, Caroli P, Scarpi E, Conteduca V, Burgio SL, Menna C, et al. (18)F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide. Eur J Nucl Med Mol Imaging. 2015;42:1276–83.

    Article  CAS  PubMed  Google Scholar 

  139. Schwarzenbock SM, Eiber M, Kundt G, Retz M, Sakretz M, Kurth J, et al. Prospective evaluation of [11C]choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2105–13.

    Article  PubMed  CAS  Google Scholar 

  140. Ceci F, Castellucci P, Graziani T, Schiavina R, Renzi R, Borghesi M, et al. (11)C-choline PET/CT in castration-resistant prostate cancer patients treated with docetaxel. Eur J Nucl Med Mol Imaging. 2016;43:84–91.

    Article  CAS  PubMed  Google Scholar 

  141. DeGrado TR, Baldwin SW, Wang S, Orr MD, Liao RP, Friedman HS, et al. Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. J Nucl Med. 2001;42:1805–14.

    CAS  PubMed  Google Scholar 

  142. Mapelli P, Incerti E, Ceci F, Castellucci P, Fanti S, Picchio M. 11C- or 18F-choline PET/CT for imaging evaluation of biochemical recurrence of prostate cancer. J Nucl Med. 2016;57:43S–8S.

    Article  PubMed  Google Scholar 

  143. Brogsitter C, Zophel K, Kotzerke J. (18)F-choline, (11)C-choline and (11)C-acetate PET/CT: comparative analysis for imaging prostate cancer patients. Eur J Nucl Med Mol Imaging. 2013;40(Suppl 1):18–27.

    Article  CAS  Google Scholar 

  144. von Eyben FE, Kairemo K. Acquisition with (11)C-choline and (18)F-fluorocholine PET/CT for patients with biochemical recurrence of prostate cancer: a systematic review and meta-analysis. Ann Nucl Med. 2016;30:385–92.

    Article  CAS  Google Scholar 

  145. Chondrogiannis S, Marzola MC, Grassetto G, Maffione AM, Rampin L, Veronese E, et al. New acquisition protocol of 18F-choline PET/CT in prostate cancer patients: review of the literature about methodology and proposal of standardization. Biomed Res Int. 2014;2014:215650.

    PubMed  PubMed Central  Google Scholar 

  146. Chondrogiannis S, Marzola MC, Grassetto G, Rampin L, Massaro A, Colletti PM, et al. Optimized protocol for (18)F-choline PET/CT in patients with biochemically relapsed prostate cancer: experiences on 250 consecutive cases. Clin Nucl Med. 2015;40:e308–12.

    Article  PubMed  Google Scholar 

  147. Kumar R, Dhanpathi H, Basu S, Rubello D, Fanti S, Alavi A. Oncologic PET tracers beyond [(18)F]FDG and the novel quantitative approaches in PET imaging. Q J Nucl Med Mol Imaging. 2008;52:50–65.

    CAS  PubMed  Google Scholar 

  148. Cimitan M, Bortolus R, Morassut S, Canzonieri V, Garbeglio A, Baresic T, et al. [18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging. 2006;33:1387–98.

    Article  PubMed  Google Scholar 

  149. Fei B, Wang H, Wu C, Chiu SM. Choline PET for monitoring early tumor response to photodynamic therapy. J Nucl Med. 2010;51:130–8.

    Article  PubMed  Google Scholar 

  150. von Eyben FE, Kairemo K, Kiljunen T, Joensuu T. Planning of external beam radiotherapy for prostate cancer guided by PET/CT. Curr Radiopharm. 2015;8:19–31.

    Article  CAS  Google Scholar 

  151. Ceci F, Castellucci P, Mapelli P, Incerti E, Picchio M, Fanti S. Evaluation of prostate cancer with 11C-choline PET/CT for treatment planning, response assessment, and prognosis. J Nucl Med. 2016;57:49S–54S.

    Article  PubMed  Google Scholar 

  152. Pinkawa M, Eble MJ, Mottaghy FM. PET and PET/CT in radiation treatment planning for prostate cancer. Expert Rev Anticancer Ther. 2011;11:1033–9.

    Article  PubMed  Google Scholar 

  153. Pinkawa M, Attieh C, Piroth MD, Holy R, Nussen S, Klotz J, et al. Dose-escalation using intensity-modulated radiotherapy for prostate cancer--evaluation of the dose distribution with and without 18F-choline PET-CT detected simultaneous integrated boost. Radiother Oncol. 2009;93:213–9.

    Article  CAS  PubMed  Google Scholar 

  154. Pinkawa M, Holy R, Piroth MD, Klotz J, Nussen S, Krohn T, et al. Intensity-modulated radiotherapy for prostate cancer implementing molecular imaging with 18F-choline PET-CT to define a simultaneous integrated boost. Strahlenther Onkol. 2010;186:600–6.

    Article  PubMed  Google Scholar 

  155. Souvatzoglou M, Krause BJ, Purschel A, Thamm R, Schuster T, Buck AK, et al. Influence of (11)C-choline PET/CT on the treatment planning for salvage radiation therapy in patients with biochemical recurrence of prostate cancer. Radiother Oncol. 2011;99:193–200.

    Article  PubMed  Google Scholar 

  156. Picchio M, Berardi G, Fodor A, Busnardo E, Crivellaro C, Giovacchini G, et al. (11)C-choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2014;41:1270–9.

    Article  CAS  PubMed  Google Scholar 

  157. Incerti E, Fodor A, Mapelli P, Fiorino C, Alongi P, Kirienko M, et al. Radiation treatment of lymph node recurrence from prostate cancer: is 11C-choline PET/CT predictive of survival outcomes? J Nucl Med. 2015;56:1836–42.

    Article  CAS  PubMed  Google Scholar 

  158. Yossepowitch O, Eggener SE, Bianco Jr FJ, Carver BS, Serio A, Scardino PT, et al. Radical prostatectomy for clinically localized, high risk prostate cancer: critical analysis of risk assessment methods. J Urol. 2007;178:493–9.

    Article  PubMed  Google Scholar 

  159. Rigatti P, Suardi N, Briganti A, Da Pozzo LF, Tutolo M, Villa L, et al. Pelvic/retroperitoneal salvage lymph node dissection for patients treated with radical prostatectomy with biochemical recurrence and nodal recurrence detected by [11C]choline positron emission tomography/computed tomography. Eur Urol. 2011;60:935–43.

    Article  PubMed  Google Scholar 

  160. Weber WA. PET/MR imaging: a critical appraisal. J Nucl Med. 2014;55:56S–8S.

    Article  CAS  PubMed  Google Scholar 

  161. Lindenberg L, Ahlman M, Turkbey B, Mena E, Choyke P. Advancement of MR and PET/MR in prostate cancer. Semin Nucl Med. 2016;46:536–43.

    Article  PubMed  Google Scholar 

  162. Bagade S, Fowler KJ, Schwarz JK, Grigsby PW, Dehdashti F. PET/MRI evaluation of gynecologic malignancies and prostate cancer. Semin Nucl Med. 2015;45:293–303.

    Article  PubMed  Google Scholar 

  163. Souvatzoglou M, Eiber M, Takei T, Furst S, Maurer T, Gaertner F, et al. Comparison of integrated whole-body [11C]choline PET/MR with PET/CT in patients with prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1486–99.

    Article  CAS  PubMed  Google Scholar 

  164. Choi JY, Yang J, Noworolski SM, Behr S, Chang AJ, Simko JP, et al. 18F Fluorocholine dynamic time-of-flight PET/MR imaging in patients with newly diagnosed intermediate- to high-risk prostate cancer: initial clinical-pathologic comparisons. Radiology. 2017;282:429–36.

    Article  PubMed  Google Scholar 

  165. Afshar-Oromieh A, Haberkorn U, Hadaschik B, Habl G, Eder M, Eisenhut M, et al. PET/MRI with a 68Ga-PSMA ligand for the detection of prostate cancer. Eur J Nucl Med Mol Imaging. 2013;40:1629–30.

    Article  PubMed  Google Scholar 

  166. Eiber M, Nekolla SG, Maurer T, Weirich G, Wester HJ, Schwaiger M. (68)Ga-PSMA PET/MR with multimodality image analysis for primary prostate cancer. Abdom Imaging. 2015;40:1769–71.

    Article  PubMed  Google Scholar 

  167. Morigi JJ, Stricker PD, van Leeuwen PJ, Tang R, Ho B, Nguyen Q, et al. Prospective comparison of 18F-Fluoromethylcholine versus 68Ga-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med. 2015;56:1185–90.

    Article  CAS  PubMed  Google Scholar 

  168. Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41:11–20.

    Article  CAS  PubMed  Google Scholar 

  169. Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen Radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57:1006–13.

    Article  PubMed  Google Scholar 

  170. Maddalena ME, Fox J, Chen J, Feng W, Cagnolini A, Linder KE, et al. 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. J Nucl Med. 2009;50:2017–24.

    Article  PubMed  Google Scholar 

  171. Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.

    Article  CAS  PubMed  Google Scholar 

  172. Yu CY, Desai B, Ji L, Groshen S, Jadvar H. Comparative performance of PET tracers in biochemical recurrence of prostate cancer: a critical analysis of literature. Am J Nucl Med Mol Imaging. 2014;4:580–601.

    PubMed  PubMed Central  Google Scholar 

  173. Ceci F, Uprimny C, Nilica B, Geraldo L, Kendler D, Kroiss A, et al. (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging. 2015;42:1284–94.

    Article  PubMed  Google Scholar 

  174. Rauscher I, Maurer T, Beer AJ, Graner FP, Haller B, Weirich G, et al. Value of 68Ga-PSMA HBED-CC PET for the assessment of lymph node metastases in prostate cancer patients with biochemical recurrence: comparison with histopathology after salvage lymphadenectomy. J Nucl Med. 2016;57:1713–9.

    Article  PubMed  Google Scholar 

  175. Bal C, Yadav MP, Ballal S. Cocktail therapy of 177Lu-PSMA-617 and 177Lu-EDTMP in patients with mCRPC: a proof-of-principle application. Clin Nucl Med. 2016;41:e386–7.

    Article  PubMed  Google Scholar 

  176. Delker A, Fendler WP, Kratochwil C, Brunegraf A, Gosewisch A, Gildehaus FJ, et al. Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:42–51.

    Article  CAS  PubMed  Google Scholar 

  177. Kwekkeboom D. Perspective on 177Lu-PSMA therapy for metastatic castration-resistant prostate cancer. J Nucl Med. 2016;57:1002–3.

    Article  PubMed  Google Scholar 

  178. Rahbar K, Bode A, Weckesser M, Avramovic N, Claesener M, Stegger L, et al. Radioligand therapy with 177Lu-PSMA-617 as a novel therapeutic option in patients with metastatic castration resistant prostate cancer. Clin Nucl Med. 2016;41:522–8.

    Article  PubMed  Google Scholar 

  179. Ahmadzadehfar H, Eppard E, Kurpig S, Fimmers R, Yordanova A, Schlenkhoff CD, et al. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. Oncotarget. 2016;7:12477–88.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Kratochwil C, Giesel FL, Stefanova M, Benesova M, Bronzel M, Afshar-Oromieh A, et al. PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with 177Lu-labeled PSMA-617. J Nucl Med. 2016;57:1170–6.

    Article  PubMed  Google Scholar 

  181. Schuster DM, Nanni C, Fanti S. Evaluation of prostate cancer with radiolabeled amino acid analogs. J Nucl Med. 2016;57:61S–6S.

    Article  PubMed  Google Scholar 

  182. Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42:432–45.

    CAS  PubMed  Google Scholar 

  183. Oka S, Hattori R, Kurosaki F, Toyama M, Williams LA, Yu W, et al. A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. J Nucl Med. 2007;48:46–55.

    CAS  PubMed  Google Scholar 

  184. Sakata T, Ferdous G, Tsuruta T, Satoh T, Baba S, Muto T, et al. L-type amino-acid transporter 1 as a novel biomarker for high-grade malignancy in prostate cancer. Pathol Int. 2009;59:7–18.

    Article  CAS  PubMed  Google Scholar 

  185. Segawa A, Nagamori S, Kanai Y, Masawa N, Oyama T. L-type amino acid transporter 1 expression is highly correlated with Gleason score in prostate cancer. Mol Clin Oncol. 2013;1:274–80.

    PubMed  Google Scholar 

  186. Odewole OA, Tade FI, Nieh PT, Savir-Baruch B, Jani AB, Master VA, et al. Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT. Eur J Nucl Med Mol Imaging. 2016;43:1773–83.

    Article  CAS  PubMed  Google Scholar 

  187. Nanni C, Zanoni L, Pultrone C, Schiavina R, Brunocilla E, Lodi F, et al. (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial. Eur J Nucl Med Mol Imaging. 2016;43:1601–10.

    Article  CAS  PubMed  Google Scholar 

  188. Ren J, Yuan L, Wen G, Yang J. The value of anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT in the diagnosis of recurrent prostate carcinoma: a meta-analysis. Acta Radiol. 2016;57:487–93.

    Article  PubMed  Google Scholar 

  189. Markwalder R, Reubi JC. Gastrin-releasing peptide receptors in the human prostate: relation to neoplastic transformation. Cancer Res. 1999;59:1152–9.

    CAS  PubMed  Google Scholar 

  190. Paes FM, Serafini AN. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin Nucl Med. 2010;40:89–104.

    Article  PubMed  Google Scholar 

  191. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23.

    Article  CAS  PubMed  Google Scholar 

  192. Mansi R, Wang X, Forrer F, Waser B, Cescato R, Graham K, et al. Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. Eur J Nucl Med Mol Imaging. 2011;38:97–107.

    Article  CAS  PubMed  Google Scholar 

  193. Dumont RA, Tamma M, Braun F, Borkowski S, Reubi JC, Maecke H, et al. Targeted radiotherapy of prostate cancer with a gastrin-releasing peptide receptor antagonist is effective as monotherapy and in combination with rapamycin. J Nucl Med. 2013;54:762–9.

    Article  CAS  PubMed  Google Scholar 

  194. Minamimoto R, Hancock S, Schneider B, Chin FT, Jamali M, Loening A, et al. Pilot comparison of (68)Ga-RM2 PET and (68)Ga-PSMA-11 PET in patients with biochemically recurrent prostate cancer. J Nucl Med. 2016;57:557–62.

    Article  PubMed  Google Scholar 

  195. Zhang H, Desai P, Koike Y, Houghton J, Carlin S, Tandon N, et al. Dual-modality imaging of prostate cancer with a fluorescent and Radiogallium-labeled gastrin-releasing peptide receptor antagonist. J Nucl Med. 2017;58:29–35.

    Article  PubMed  PubMed Central  Google Scholar 

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Giovacchini, G., Giovannini, E., Leoncini, R. et al. PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies. Eur J Nucl Med Mol Imaging 44, 1751–1776 (2017). https://doi.org/10.1007/s00259-017-3700-x

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  • DOI: https://doi.org/10.1007/s00259-017-3700-x

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