Skip to main content

Advertisement

SpringerLink
Log in

Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Amino acids are required nutrients for proliferating tumor cells, and amino acid transport is upregulated in many tumor types. Studies of radiolabeled amino acids in animals and humans demonstrate that amino acid based tracers have advantageous characteristics relative to 2-[18F]fluoro-2-deoxyglucose in certain tumors, particularly brain gliomas. Non-natural amino acids for tumor imaging generally have greater metabolic stability and can be labeled with longer-lived radionuclides for positron emission tomography and single photon emission computed tomography such as fluorine-18 and iodine-123. Amino acids enter cells via amino acid transport with varying selectivity based on their chemical structure. This review focuses on the rationale, biological basis, current status and future prospects of radiolabeled non-natural amino acids for tumor imaging and discusses various classes of these compounds including aromatic, alicyclic and α,α-dialkyl amino acids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Bombardieri, E., Aliberti, G., de Graaf, C., Pauwels, E., & Crippa, F. (2001). Positron emission tomography (PET) and other nuclear medicine modalities in staging gastrointestinal cancer. Seminar in Surgical Oncology, 20, 134–146.

    CAS  Google Scholar 

  2. Schirrmeister, H., Kuhn, T., Guhlmann, A., Santjohanser, C., Horster, T., Nussle, K., et al. (2001). Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures. European Journal of Nuclear Medicine, 28, 351–358.

    PubMed  CAS  Google Scholar 

  3. Stokkel, M. P., Draisma, A., & Pauwels, E. K. (2001). Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology. Part IIIb: therapy response monitoring in colorectal and lung tumours, head and neck cancer, hepatocellular carcinoma and sarcoma. Journal of Cancer Research and Clinical Oncology, 127, 278–285.

    PubMed  CAS  Google Scholar 

  4. van der Hiel, B., Pauwels, E. K., & Stokkel, M. P. (2001). Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology. Part IIIa: therapy response monitoring in breast cancer, lymphoma and gliomas. Journal of Cancer Research and Clinical Oncology, 127, 269–277.

    PubMed  Google Scholar 

  5. Juweid, M. E., & Cheson, B. D. (2006). Positron-emission tomography and assessment of cancer therapy. New England Journal of Medicine, 354, 496–507.

    PubMed  CAS  Google Scholar 

  6. Czernin, J., Allen-Auerbach, M., & Schelbert, H. R. (2007). Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. Journal of Nuclear Medicine, 48(Suppl 1), 78S–88S.

    PubMed  CAS  Google Scholar 

  7. Pauwels, E. K., Ribeiro, M. J., Stoot, J. H., McCready, V. R., Bourguignon, M., & Maziere, B. (1998). FDG accumulation and tumor biology. Nuclear Medicine and Biology, 25, 317–322.

    PubMed  CAS  Google Scholar 

  8. Podoloff, D. A., Advani, R. H., Allred, C., Benson 3rd, A. B., Brown, E., Burstein, H. J., Carlson, R. W., et al. (2007). NCCN task force report: positron emission tomography (PET)/computed tomography (CT) scanning in cancer. Journal of the National Comprehensive Cancer Network, 5(Suppl 1), S1–S22, quiz S23–22.

    PubMed  Google Scholar 

  9. Fowler, J. S., Hoffman, E. J., & Larson, S. M. (1988). Cyclotrons and radiopharmaceuticals in positron emission tomography. Council on scientific affairs. Report of the positron emission tomography panel. JAMA, 259, 1854–1860.

    Google Scholar 

  10. Hillner, B. E., Liu, D., Coleman, R. E., Shields, A. F., Gareen, I. F., Hanna, L., et al. (2007). The National Oncologic PET Registry (NOPR): design and analysis plan. Journal of Nuclear Medicine, 48, 1901–1908.

    PubMed  Google Scholar 

  11. Lindsay, M. J., Siegel, B. A., Tunis, S. R., Hillner, B. E., Shields, A. F., Carey, B. P., et al. (2007). The National Oncologic PET Registry: expanded Medicare coverage for PET under coverage with evidence development. American Journal of Roentgenology, 188, 1109–1113.

    PubMed  Google Scholar 

  12. Yap, C. S., Schiepers, C., Fishbein, M. C., Phelps, M. E., & Czernin, J. (2002). FDG-PET imaging in lung cancer: how sensitive is it for bronchioloalveolar carcinoma? European Journal of Nuclear Medicine and Molecular Imaging, 29, 1166–1173.

    PubMed  CAS  Google Scholar 

  13. Salskov, A., Tammisetti, V. S., Grierson, J., & Vesselle, H. (2007). FLT: measuring tumor cell proliferation in vivo with positron emission tomography and 3′-deoxy-3′-[18F]fluorothymidine. Seminars in Nuclear Medicine, 37, 429–439.

    PubMed  Google Scholar 

  14. Sundararajan, L., Linden, H. M., Link, J. M., Krohn, K. A., & Mankoff, D. A. (2007). 18F-fluoroestradiol. Seminars in Nuclear Medicine, 37, 470–476.

    PubMed  Google Scholar 

  15. Benard, F., & Turcotte, E. (2005). Imaging in breast cancer: single-photon computed tomography and positron-emission tomography. Breast Cancer Research, 7, 153–162.

    PubMed  CAS  Google Scholar 

  16. Van Den Bossche, B., & Van de Wiele, C. (2004). Receptor imaging in oncology by means of nuclear medicine: current status. Journal of Clinical Oncology, 22, 3593–3607.

    Google Scholar 

  17. Eubank, W. B., & Mankoff, D. A. (2004). Current and future uses of positron emission tomography in breast cancer imaging. Seminars in Nuclear Medicine, 34, 224–240.

    PubMed  Google Scholar 

  18. Mach, R. H., & Wheeler, K. T. (2007). Imaging the proliferative status of tumors with PET. Journal of Labelled Compounds & Radiopharmaceuticals, 50, 366–369.

    CAS  Google Scholar 

  19. Lee, S. T., & Scott, A. M. (2007). Hypoxia positron emission tomography imaging with 18F-fluoromisonidazole. Seminars in Nuclear Medicine, 37, 451–461.

    PubMed  Google Scholar 

  20. Vavere, A. L., & Lewis, J. S. (2007). Cu-ATSM: a radiopharmaceutical for the PET imaging of hypoxia. Dalton Transactions, 43, 4893–4902.

    Google Scholar 

  21. Grigsby, P. W., Malyapa, R. S., Higashikubo, R., Schwarz, J. K., Welch, M. J., Huettner, P. C., et al. (2007). Comparison of molecular markers of hypoxia and imaging with 60Cu-ATSM in cancer of the uterine cervix. Molecular Imaging Biology, 9, 278–283.

    Google Scholar 

  22. Schiff, D., Brown, P. D., & Giannini, C. (2007). Outcome in adult low-grade glioma: the impact of prognostic factors and treatment. Neurology, 69, 1366–1373.

    PubMed  Google Scholar 

  23. Norden, A. D., & Wen, P. Y. (2006). Glioma therapy in adults. Neurologist, 12, 279–292.

    PubMed  Google Scholar 

  24. Chen, W. (2007). Clinical applications of PET in brain tumors. Journal of Nuclear Medicine, 48, 1468–1481.

    PubMed  Google Scholar 

  25. Healy, M. E., Hesselink, J. R., Press, G. A., & Middleton, M. S. (1987). Increased detection of intracranial metastases with intravenous Gd-DTPA. Radiology, 165, 619–624.

    PubMed  CAS  Google Scholar 

  26. Graif, M., Bydder, G. M., Steiner, R. E., Niendorf, P., Thomas, D. G., & Young, I. R. (1985). Contrast-enhanced MR imaging of malignant brain tumors. American Journal of Neuroradiology, 6, 855–862.

    PubMed  CAS  Google Scholar 

  27. Claussen, C., Laniado, M., Schorner, W., Niendorf, H. P., Weinmann, H. J., Fiegler, W., et al. (1985). Gadolinium-DTPA in MR imaging of glioblastomas and intracranial metastases. American Journal of Neuroradiology, 6, 669–674.

    PubMed  CAS  Google Scholar 

  28. Bradley Jr., W. G., Waluch, V., Yadley, R. A., & Wycoff, R. R. (1984). Comparison of CT and MR in 400 patients with suspected disease of the brain and cervical spinal cord. Radiology, 152, 695–702.

    PubMed  Google Scholar 

  29. Marks, J. E., & Gado, M. (1977). Serial computed tomography of primary brain tumors following surgery, irradiation, and chemotherapy. Radiology, 125, 119–125.

    PubMed  CAS  Google Scholar 

  30. Padma, M. V., Said, S., Jacobs, M., Hwang, D. R., Dunigan, K., Satter, M., et al. (2003). Prediction of pathology and survival by FDG PET in gliomas. Journal of Neuro-oncology, 64, 227–237.

    PubMed  CAS  Google Scholar 

  31. De Witte, O., Levivier, M., Violon, P., Salmon, I., Damhaut, P., Wikler Jr., D., et al. (1996). Prognostic value positron emission tomography with [18F]fluoro-2-deoxy-D-glucose in the low-grade glioma. Neurosurgery, 39, 470–476, discussion 476–477.

    PubMed  Google Scholar 

  32. Alavi, J. B., Alavi, A., Chawluk, J., Kushner, M., Powe, J., Hickey, W., et al. (1988). Positron emission tomography in patients with glioma. A predictor of prognosis. Cancer, 62, 1074–1078.

    PubMed  CAS  Google Scholar 

  33. Patronas, N. J., Di Chiro, G., Brooks, R. A., DeLaPaz, R. L., Kornblith, P. L., Smith, B. H., et al. (1982). Work in progress: [18F] fluorodeoxyglucose and positron emission tomography in the evaluation of radiation necrosis of the brain. Radiology, 144, 885–889.

    PubMed  CAS  Google Scholar 

  34. Doyle, W. K., Budinger, T. F., Valk, P. E., Levin, V. A., & Gutin, P. H. (1987). Differentiation of cerebral radiation necrosis from tumor recurrence by [18F]FDG and 82Rb positron emission tomography. Journal of Computer Assisted Tomography, 11, 563–570.

    PubMed  CAS  Google Scholar 

  35. Rozental, J. M., Levine, R. L., Nickles, R. J., & Dobkin, J. A. (1989). Glucose uptake by gliomas after treatment. A positron emission tomographic study. Archives of Neurology, 46, 1302–1307.

    PubMed  CAS  Google Scholar 

  36. Patronas, N. J., Di Chiro, G., Kufta, C., Bairamian, D., Kornblith, P. L., Simon, R., et al. (1985). Prediction of survival in glioma patients by means of positron emission tomography. Journal of Neurosurgery, 62, 816–822.

    Article  PubMed  CAS  Google Scholar 

  37. Ricci, P. E., Karis, J. P., Heiserman, J. E., Fram, E. K., Bice, A. N., & Drayer, B. P. (1998). Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography? American Journal of Neuroradiology, 19, 407–413.

    PubMed  CAS  Google Scholar 

  38. Hofer, C., Laubenbacher, C., Block, T., Breul, J., Hartung, R., & Schwaiger, M. (1999). Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. European Urology, 36, 31–35.

    PubMed  CAS  Google Scholar 

  39. Nunez, R., Macapinlac, H. A., Yeung, H. W., Akhurst, T., Cai, S., Osman, I., et al. (2002). Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer. Journal of Nuclear Medicine, 43, 46–55.

    PubMed  Google Scholar 

  40. Hawkins, R. A., Huang, S. C., Barrio, J. R., Keen, R. E., Feng, D., Mazziotta, J. C., et al. (1989). Estimation of local cerebral protein synthesis rates with L-[1–11C]leucine and PET: methods, model, and results in animals and humans. Journal of Cerebral Blood Flow and Metabolism, 9, 446–460.

    PubMed  CAS  Google Scholar 

  41. Barrio, J. R., Keen, R. E., Ropchan, J. R., MacDonald, N. S., Baumgartner, F. J., Padgett, H. C., et al. (1983). L-[1–11C]leucine: routine synthesis by enzymatic resolution. Journal of Nuclear Medicine, 24, 515–521.

    PubMed  CAS  Google Scholar 

  42. Leskinen-Kallio, S., Nagren, K., Lehikoinen, P., Ruotsalainen, U., Teras, M., & Joensuu, H. (1992). Carbon-11-methionine and PET is an effective method to image head and neck cancer. Journal of Nuclear Medicine, 33, 691–695.

    PubMed  CAS  Google Scholar 

  43. Inoue, T., Kim, E. E., Wong, F. C., Yang, D. J., Bassa, P., Wong, W. H., et al. (1996). Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors. Journal of Nuclear Medicine, 37, 1472–1476.

    PubMed  CAS  Google Scholar 

  44. Bolster, J. M., Vaalburg, W., Paans, A. M., van Dijk, T. H., Elsinga, P. H., Zijlstra, J. B., et al. (1986). Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET). European Journal of Nuclear Medicine, 12, 321–324.

    PubMed  CAS  Google Scholar 

  45. de Wolde, H., Pruim, J., Mastik, M. F., Koudstaal, J., & Molenaar, W. M. (1997). Proliferative activity in human brain tumors: comparison of histopathology and L-[1–11C]tyrosine PET. Journal of Nuclear Medicine, 38, 1369–1374.

    PubMed  Google Scholar 

  46. Ericson, K., Lilja, A., Bergstrom, M., Collins, V. P., Eriksson, L., Ehrin, E., et al. (1985). Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors. Journal of Computer Assisted Tomography, 9, 683–689.

    PubMed  CAS  Google Scholar 

  47. Lilja, A., Bergstrom, K., Hartvig, P., Spannare, B., Halldin, C., Lundqvist, H., et al. (1985). Dynamic study of supratentorial gliomas with L-methyl-11C-methionine and positron emission tomography. American Journal of Neuroradiology, 6, 505–514.

    PubMed  CAS  Google Scholar 

  48. Derlon, J. M., Bourdet, C., Bustany, P., Chatel, M., Theron, J., Darcel, F., et al. (1989). [11C]L-methionine uptake in gliomas. Neurosurgery, 25, 720–728.

    PubMed  CAS  Google Scholar 

  49. Kameyama, M., Shirane, R., Itoh, J., Sato, K., Katakura, R., Yoshimoto, T., et al. (1990). The accumulation of 11C-methionine in cerebral glioma patients studied with PET. Acta Neurochirurgica (Wien), 104, 8–12.

    CAS  Google Scholar 

  50. Mackenzie, B., & Erickson, J. D. (2004). Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family. Pflugers Archiv, 447, 784–795.

    PubMed  CAS  Google Scholar 

  51. Palacin, M., Estevez, R., Bertran, J., & Zorzano, A. (1998). Molecular biology of mammalian plasma membrane amino acid transporters. Physiological Reviews, 78, 969–1054.

    PubMed  CAS  Google Scholar 

  52. Verrey, F. (2003). System L: heteromeric exchangers of large, neutral amino acids involved in directional transport. Pflugers Archiv, 445, 529–533.

    PubMed  CAS  Google Scholar 

  53. Wagner, C. A., Lang, F., & Broer, S. (2001). Function and structure of heterodimeric amino acid transporters. American Journal of Physiology. Cell Physiology, 281, C1077–C1093.

    PubMed  CAS  Google Scholar 

  54. Ishiwata, K., Kubota, K., Murakami, M., Kubota, R., & Senda, M. (1993). A comparative study on protein incorporation of L-[methyl-3H]methionine, L-[1–14C]leucine and L-2-[18F]fluorotyrosine in tumor bearing mice. Nuclear Medicine and Biology, 20, 895–899.

    PubMed  CAS  Google Scholar 

  55. Jager, P. L., Vaalburg, W., Pruim, J., de Vries, E. G., Langen, K. J., & Piers, D. A. (2001). Radiolabeled amino acids: basic aspects and clinical applications in oncology. Journal of Nuclear Medicine, 42, 432–445.

    PubMed  CAS  Google Scholar 

  56. Langen, K. J., & Broer, S. (2004). Molecular transport mechanisms of radiolabeled amino acids for PET and SPECT. Journal of Nuclear Medicine, 45, 1435–1436.

    PubMed  CAS  Google Scholar 

  57. Paans, A. M., Pruim, J., van Waarde, A., Willemsen, A. T., & Vaalburg, W. (1996). Radiolabelled-tyrosine for the measurement of protein synthesis rate in vivo by positron emission tomography. Bailliere’s Clinical Endocrinology and Metabolism, 10, 497–510.

    PubMed  CAS  Google Scholar 

  58. Smith, C. B., Schmidt, K. C., Qin, M., Burlin, T. V., Cook, M. P., Kang, J., et al. (2005). Measurement of regional rates of cerebral protein synthesis with L-[1–11C]leucine and PET with correction for recycling of tissue amino acids: II. Validation in rhesus monkeys. Journal of Cerebral Blood Flow and Metabolism, 25, 629–640.

    PubMed  CAS  Google Scholar 

  59. Sundaram, S. K., Muzik, O., Chugani, D. C., Mu, F., Mangner, T. J., & Chugani, H. T. (2006). Quantification of protein synthesis in the human brain using L-[1–11C]-leucine PET: incorporation of factors for large neutral amino acids in plasma and for amino acids recycled from tissue. Journal of Nuclear Medicine, 47, 1787–1795.

    PubMed  CAS  Google Scholar 

  60. Pruim, J., Willemsen, A. T., Molenaar, W. M., van Waarde, A., Paans, A. M., Heesters, M. A., et al. (1995). Brain tumors: L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate. Radiology, 197, 221–226.

    PubMed  CAS  Google Scholar 

  61. Fuchs, B. C., & Bode, B. P. (2005). Amino acid transporters ASCT2 and LAT1 in cancer: partners in crime? Seminars in Cancer Biology, 15, 254–266.

    PubMed  CAS  Google Scholar 

  62. Uchino, H., Kanai, Y., Kim, D. K., Wempe, M. F., Chairoungdua, A., Morimoto, E., et al. (2002). Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Molecular Pharmacology, 61, 729–737.

    PubMed  CAS  Google Scholar 

  63. Franchi-Gazzola, R., Dall’Asta, V., Sala, R., Visigalli, R., Bevilacqua, E., Gaccioli, F., et al. (2006). The role of the neutral amino acid transporter SNAT2 in cell volume regulation. Acta physiologica (Oxf), 187, 273–283.

    CAS  Google Scholar 

  64. Franchi-Gazzola, R., Gaccioli, F., Bevilacqua, E., Visigalli, R., Dall’Asta, V., Sala, R., et al. (2004). The synthesis of SNAT2 transporters is required for the hypertonic stimulation of system A transport activity. Biochimica et Biophysica Acta, 1667, 157–166.

    PubMed  CAS  Google Scholar 

  65. Hyde, R., Taylor, P. M., & Hundal, H. S. (2003). Amino acid transporters: roles in amino acid sensing and signalling in animal cells. Biochemical Journal, 373, 1–18.

    PubMed  CAS  Google Scholar 

  66. Christensen, H. N., Oxender, D. L., Liang, M., & Vatz, K. A. (1965). The use of N-methylation to direct route of mediated transport of amino acids. Journal of Biological Chemistry, 240, 3609–3616.

    PubMed  CAS  Google Scholar 

  67. Shotwell, M. A., Kilberg, M. S., & Oxender, D. L. (1983). The regulation of neutral amino acid transport in mammalian cells. Biochimica et Biophysica Acta, 737, 267–284.

    PubMed  CAS  Google Scholar 

  68. Kanai, Y., & Hediger, M. A. (2003). The glutamate and neutral amino acid transporter family: physiological and pharmacological implications. European Journal of Pharmacology, 479, 237–247.

    PubMed  CAS  Google Scholar 

  69. Kanai, Y., & Hediger, M. A. (2004). The glutamate/neutral amino acid transporter family SLC1: molecular, physiological and pharmacological aspects. Pflugers Archiv, 447, 469–479.

    PubMed  CAS  Google Scholar 

  70. Heiss, P., Mayer, S., Herz, M., Wester, H. J., Schwaiger, M., & Senekowitsch-Schmidtke, R. (1999). Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. Journal of Nuclear Medicine, 40, 1367–1373.

    PubMed  CAS  Google Scholar 

  71. Langen, K. J., Hamacher, K., Bauer, D., Broer, S., Pauleit, D., Herzog, H., et al. (2005). Preferred stereoselective transport of the D-isomer of cis-4-[18F]fluoro-proline at the blood-brain barrier. Journal of Cerebral Blood Flow and Metabolism, 25, 607–616.

    PubMed  CAS  Google Scholar 

  72. Tsukada, H., Sato, K., Fukumoto, D., & Kakiuchi, T. (2006). Evaluation of D-isomers of O-18F-fluoromethyl, O-18F-fluoroethyl and O-18F-fluoropropyl tyrosine as tumour imaging agents in mice. European Journal of Nuclear Medicine and Molecular Imaging, 33, 1017–1024.

    PubMed  CAS  Google Scholar 

  73. Tsukada, H., Sato, K., Fukumoto, D., Nishiyama, S., Harada, N., & Kakiuchi, T. (2006). Evaluation of D-isomers of O-11C-methyl tyrosine and O-18F-fluoromethyl tyrosine as tumor-imaging agents in tumor-bearing mice: comparison with L- and D-11C-methionine. Journal of Nuclear Medicine, 47, 679–688.

    PubMed  CAS  Google Scholar 

  74. Kersemans, V., Cornelissen, B., Kersemans, K., Bauwens, M., Dierckx, R. A., De Spiegeleer, B., et al. (2006). 123/125I-labelled 2-iodo-L-phenylalanine and 2-iodo-D-phenylalanine: comparative uptake in various tumour types and biodistribution in mice. European Journal of Nuclear Medicine and Molecular Imaging, 33, 919–927.

    PubMed  CAS  Google Scholar 

  75. Bauwens, M., Keyaerts, M., Lahoutte, T., Kersemans, K., Caveliers, V., Bossuyt, A., et al. (2007). Intra-individual comparison of the human biodistribution and dosimetry of the D and L isomers of 2-[123I]iodo-phenylalanine. Nuclear Medicine Communications, 28, 823–828.

    PubMed  CAS  Google Scholar 

  76. Martarello, L., McConathy, J., Camp, V. M., Malveaux, E. J., Simpson, N. E., Simpson, C. P., et al. (2002). Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC), potential PET ligands for tumor detection. Journal of Medicinal Chemistry, 45, 2250–2259.

    PubMed  CAS  Google Scholar 

  77. Yu, W., McConathy, J., Olson, J., Camp, V. M., & Goodman, M. M. (2007). Facile stereospecific synthesis and biological evaluation of (S)- and (R)-2-Amino-2-methyl-4-[123I]iodo-3-(E)-butenoic acid for brain tumor imaging with single photon emission computerized tomography. Journal of Medicinal Chemistry, 50, 6718–6721.

    PubMed  CAS  Google Scholar 

  78. Laverman, P., Boerman, O. C., Corstens, F. H., & Oyen, W. J. (2002). Fluorinated amino acids for tumour imaging with positron emission tomography. European Journal of Nuclear Medicine and Molecular Imaging, 29, 681–690.

    PubMed  CAS  Google Scholar 

  79. Saier Jr., M. H., Daniels, G. A., Boerner, P., & Lin, J. (1988). Neutral amino acid transport systems in animal cells: potential targets of oncogene action and regulators of cellular growth. Journal of Membrane Biology, 104, 1–20.

    PubMed  CAS  Google Scholar 

  80. Lin, J., Raoof, D. A., Thomas, D. G., Greenson, J. K., Giordano, T. J., Robinson, G. S., et al. (2004). L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett’s adenocarcinoma. Neoplasia, 6, 74–84.

    PubMed  CAS  Google Scholar 

  81. Yanagida, O., Kanai, Y., Chairoungdua, A., Kim, D. K., Segawa, H., Nii, T., et al. (2001). Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochimica et Biophysica Acta, 1514, 291–302.

    PubMed  CAS  Google Scholar 

  82. Esseghir, S., Reis-Filho, J. S., Kennedy, A., James, M., O’Hare, M. J., Jeffery, R., et al. (2006). Identification of transmembrane proteins as potential prognostic markers and therapeutic targets in breast cancer by a screen for signal sequence encoding transcripts. Journal of Pathology, 210, 420–430.

    PubMed  CAS  Google Scholar 

  83. Nawashiro, H., Otani, N., Shinomiya, N., Fukui, S., Ooigawa, H., Shima, K., et al. (2006). L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors. International Journal of Cancer, 119, 484–492.

    CAS  Google Scholar 

  84. Li, R., Younes, M., Frolov, A., Wheeler, T. M., Scardino, P., Ohori, M., et al. (2003). Expression of neutral amino acid transporter ASCT2 in human prostate. Anticancer Research, 23, 3413–3418.

    PubMed  CAS  Google Scholar 

  85. Witte, D., Ali, N., Carlson, N., & Younes, M. (2002). Overexpression of the neutral amino acid transporter ASCT2 in human colorectal adenocarcinoma. Anticancer Research, 22, 2555–2557.

    PubMed  CAS  Google Scholar 

  86. Fuchs, B. C., Finger, R. E., Onan, M. C., & Bode, B. P. (2007). ASCT2 silencing regulates mammalian target-of-rapamycin growth and survival signaling in human hepatoma cells. American Journal of Physiology. Cell Physiology, 293, C55–C63.

    PubMed  CAS  Google Scholar 

  87. Beugnet, A., Tee, A. R., Taylor, P. M., & Proud, C. G. (2003). Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability. Biochemical Journal, 372, 555–566.

    PubMed  CAS  Google Scholar 

  88. Esslinger, C. S., Cybulski, K. A., & Rhoderick, J. F. (2005). N-gamma-aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site. Bioorganic & Medicinal Chemistry, 13, 1111–1118.

    CAS  Google Scholar 

  89. Grewer, C., & Grabsch, E. (2004). New inhibitors for the neutral amino acid transporter ASCT2 reveal its Na+ -dependent anion leak. Journal of Physiology, 557, 747–759.

    PubMed  CAS  Google Scholar 

  90. Kersemans, K., Bauwens, M., Lahoutte, T., Bossuyt, A., & Mertens, J. (2007). In vivo PET evaluation in tumour-bearing rats of 2-[18F]fluoromethyl-L-phenylalanine as a new potential tracer for molecular imaging of brain and extra-cranial tumours in humans with PET. Nuclear Instruments & Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment, 571, 151–154.

    CAS  Google Scholar 

  91. Keyaerts, M., Lahoutte, T., Neyns, B., Caveliers, V., Vanhove, C., Everaert, H., et al. (2007). 123I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients. European Journal of Nuclear Medicine and Molecular Imaging, 34, 994–1002.

    PubMed  CAS  Google Scholar 

  92. Moon, B. S., Lee, T. S., Lee, K. C., An, G. I., Cheon, G. J., Lim, S. M., et al. (2007). Syntheses of F-18 labeled fluoroalkyltyrosine derivatives and their biological evaluation in rat bearing 9 L tumor. Bioorganic & Medicinal Chemistry Letters, 17, 200–204.

    CAS  Google Scholar 

  93. Rutten, I., Cabay, J. E., Withofs, N., Lemaire, C., Aerts, J., Baart, V., et al. (2007). PET/CT of skull base meningiomas using 2–18F-fluoro-L-tyrosine: initial report. Journal of Nuclear Medicine, 48, 720–725.

    PubMed  CAS  Google Scholar 

  94. Langen, K. J., Pauleit, D., & Coenen, H. H. (2002). 3-[123I]Iodo-alpha-methyl-L-tyrosine: uptake mechanisms and clinical applications. Nuclear Medicine and Biology, 29, 625–631.

    PubMed  CAS  Google Scholar 

  95. Lahoutte, T., Caveliers, V., Camargo, S. M., Franca, R., Ramadan, T., Veljkovic, E., et al. (2004). SPECT and PET amino acid tracer influx via system L (h4F2hc-hLAT1) and its transstimulation. Journal of Nuclear Medicine, 45, 1591–1596.

    PubMed  CAS  Google Scholar 

  96. Riemanna, B., Kopka, K., Stogbauer, F., Halfter, H., Ketteler, S., Phan, T. Q. V., et al. (2001). Kinetic parameters of 3-[123I]iodo-L-a-methyl tyrosine ([123I]IMT) transport in human GOS3 glioma cells. Nuclear Medicine and Biology, 28, 293–297.

    CAS  Google Scholar 

  97. Shikano, N., Kanai, Y., Kawai, K., Ishikawa, N., & Endou, H. (2003). Characterization of 3-[125I]iodo-alpha-methyl-L-tyrosine transport via human L-type amino acid transporter 1. Nuclear Medicine and Biology, 30, 31–37.

    PubMed  CAS  Google Scholar 

  98. Shikano, N., Kanai, Y., Kawai, K., Inatomi, J., Kim, D. K., Ishikawa, N., et al. (2003). Isoform selectivity of 3-125I-iodo-alpha-methyl-L-tyrosine membrane transport in human L-type amino acid transporters. Journal of Nuclear Medicine, 44, 244–246.

    PubMed  CAS  Google Scholar 

  99. Franzius, C., Kopka, K., van Valen, F., Eckervogt, V., Riemann, B., Sciuk, J., et al. (2001). Characterization of 3-[123I]iodo-L-alpha-methyl tyrosine ([123I]IMT) transport into human Ewing’s sarcoma cells in vitro. Nuclear Medicine and Biology, 28, 123–128.

    PubMed  CAS  Google Scholar 

  100. Lahoutte, T., Caveliers, V., Dierickx, L., Vekeman, M., Everaert, H., Mertens, J., et al. (2001). In vitro characterization of the influx of 3-[125I]iodo-L-alpha-methyltyrosine and 2-[125I]iodo-L-tyrosine into U266 human myeloma cells: evidence for system T transport. Nuclear Medicine and Biology, 28, 129–134.

    PubMed  CAS  Google Scholar 

  101. Matte, G., Sangster, S. M., Acker, M., Hudgins, M., & Too, C. K. (2005). Characterization of 123I-iodo-alpha-methyltyrosine transport in rat lymphoma cells. Nuclear Medicine and Biology, 32, 67–73.

    PubMed  CAS  Google Scholar 

  102. Schmidt, D., Langen, K. J., Herzog, H., Wirths, J., Holschbach, M., Kiwit, J. C., et al. (1997). Whole-body kinetics and dosimetry of L-3-123I-iodo-alpha-methyltyrosine. European Journal of Nuclear Medicine, 24, 1162–1166.

    PubMed  CAS  Google Scholar 

  103. Langen, K. J., Clauss, R. P., Holschbach, M., Muhlensiepen, H., Kiwit, J. C., Zilles, K., et al. (1998). Comparison of iodotyrosines and methionine uptake in a rat glioma model. Journal of Nuclear Medicine, 39, 1596–1599.

    PubMed  CAS  Google Scholar 

  104. Langen, K. J., Ziemons, K., Kiwit, J. C., Herzog, H., Kuwert, T., Bock, W. J., et al. (1997). 3-[123I]iodo-alpha-methyltyrosine and [methyl-11C]-L-methionine uptake in cerebral gliomas: a comparative study using SPECT and PET. Journal of Nuclear Medicine, 38, 517–522.

    PubMed  CAS  Google Scholar 

  105. Langen, K. J., Coenen, H. H., Roosen, N., Kling, P., Muzik, O., Herzog, H., et al. (1990). SPECT studies of brain tumors with L-3-[123I] iodo-alpha-methyl tyrosine: comparison with PET, 124IMT and first clinical results. Journal of Nuclear Medicine, 31, 281–286.

    PubMed  CAS  Google Scholar 

  106. Grosu, A. L., Weber, W., Feldmann, H. J., Wuttke, B., Bartenstein, P., Gross, M. W., et al. (2000). First experience with I-123-alpha-methyl-tyrosine SPECT in the 3-D radiation treatment planning of brain gliomas. International Journal of Radiation Oncology, Biology, Physics, 47, 517–526.

    PubMed  CAS  Google Scholar 

  107. Grosu, A. L., Weber, W. A., Franz, M., Stark, S., Piert, M., Thamm, R., et al. (2005). Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. International Journal of Radiation Oncology, Biology, Physics, 63, 511–519.

    PubMed  CAS  Google Scholar 

  108. Bader, J. B., Samnick, S., Moringlane, J. R., Feiden, W., Schaefer, A., Kremp, S., et al. (1999). Evaluation of l-3-[123I]iodo-alpha-methyltyrosine SPET and [18F]fluorodeoxyglucose PET in the detection and grading of recurrences in patients pretreated for gliomas at follow-up: a comparative study with stereotactic biopsy. European Journal of Nuclear Medicine, 26, 144–151.

    PubMed  CAS  Google Scholar 

  109. Kuwert, T., Woesler, B., Morgenroth, C., Lerch, H., Schafers, M., Palkovic, S., et al. (1998). Diagnosis of recurrent glioma with SPECT and iodine-123-alpha-methyl tyrosine. Journal of Nuclear Medicine, 39, 23–27.

    PubMed  CAS  Google Scholar 

  110. Weber, W. A., Dick, S., Reidl, G., Dzewas, B., Busch, R., Feldmann, H. J., et al. (2001). Correlation between postoperative 3-[123I]iodo-L-alpha-methyltyrosine uptake and survival in patients with gliomas. Journal of Nuclear Medicine, 42, 1144–1150.

    PubMed  CAS  Google Scholar 

  111. Henze, M., Mohammed, A., Schlemmer, H. P., Herfarth, K. K., Hoffner, S., Haufe, S., et al. (2004). PET and SPECT for detection of tumor progression in irradiated low-grade astrocytoma: a receiver-operating-characteristic analysis. Journal of Nuclear Medicine, 45, 579–586.

    PubMed  Google Scholar 

  112. Kuwert, T., Morgenroth, C., Woesler, B., Matheja, P., Palkovic, S., Vollet, B., et al. (1996). Uptake of iodine-123-alpha-methyl tyrosine by gliomas and non-neoplastic brain lesions. European Journal of Nuclear Medicine, 23, 1345–1353.

    PubMed  CAS  Google Scholar 

  113. Lang, K., Kloska, S., Straeter, R., Rickert, C. H., Goder, G., Kurlemann, G., et al. (2005). [Clinical value of amino acid imaging in paediatric brain tumours. Comparison with MRI]. Nuklearmedizin, 44, 131–136.

    PubMed  CAS  Google Scholar 

  114. Riemann, B., Papke, K., Hoess, N., Kuwert, T., Weckesser, M., Matheja, P., et al. (2002). Noninvasive grading of untreated gliomas: a comparative study of MR imaging and 3-[123I]iodo-L-alpha-methyltyrosine SPECT. Radiology, 225, 567–574.

    PubMed  Google Scholar 

  115. Schmidt, D., Gottwald, U., Langen, K. J., Weber, F., Hertel, A., Floeth, F., et al. (2001). 3-[123I]Iodo-alpha-methyl-L-tyrosine uptake in cerebral gliomas: relationship to histological grading and prognosis. European Journal of Nuclear Medicine, 28, 855–861.

    PubMed  CAS  Google Scholar 

  116. Kuwert, T., Probst-Cousin, S., Woesler, B., Morgenroth, C., Lerch, H., Matheja, P., et al. (1997). Iodine-123-alpha-methyl tyrosine in gliomas: correlation with cellular density and proliferative activity. Journal of Nuclear Medicine, 38, 1551–1555.

    PubMed  CAS  Google Scholar 

  117. Woesler, B., Kuwert, T., Morgenroth, C., Matheja, P., Palkovic, S., Schafers, M., et al. (1997). Non-invasive grading of primary brain tumours: results of a comparative study between SPET with 123I-alpha-methyl tyrosine and PET with 18F-deoxyglucose. European Journal of Nuclear Medicine, 24, 428–434.

    PubMed  CAS  Google Scholar 

  118. Kuczer, D., Feussner, A., Wurm, R., Wust, P., Michel, R., Stockhammer, F., et al. (2007). 123I-IMT SPECT for evaluation of the response to radiation therapy in high grade gliomas: a feasibility study. British Journal of Radiology, 80, 274–278.

    PubMed  CAS  Google Scholar 

  119. Langen, K. J., Hamacher, K., Weckesser, M., Floeth, F., Stoffels, G., Bauer, D., et al. (2006). O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications. Nuclear Medicine and Biology, 33, 287–294.

    PubMed  CAS  Google Scholar 

  120. Langen, K. J., Jarosch, M., Muhlensiepen, H., Hamacher, K., Broer, S., Jansen, P., et al. (2003). Comparison of fluorotyrosines and methionine uptake in F98 rat gliomas. Nuclear Medicine and Biology, 30, 501–508.

    PubMed  CAS  Google Scholar 

  121. Wester, H. J., Herz, M., Weber, W., Heiss, P., Senekowitsch-Schmidtke, R., Schwaiger, M., et al. (1999). Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. Journal of Nuclear Medicine, 40, 205–212.

    PubMed  CAS  Google Scholar 

  122. Pauleit, D., Floeth, F., Herzog, H., Hamacher, K., Tellmann, L., Muller, H. W., et al. (2003). Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-L-tyrosine. European Journal of Nuclear Medicine and Molecular Imaging, 30, 519–524.

    PubMed  CAS  Google Scholar 

  123. Kaim, A. H., Weber, B., Kurrer, M. O., Westera, G., Schweitzer, A., Gottschalk, J., et al. (2002). 18F-FDG and 18F-FET uptake in experimental soft tissue infection. European Journal of Nuclear Medicine and Molecular Imaging, 29, 648–654.

    PubMed  CAS  Google Scholar 

  124. Rau, F. C., Weber, W. A., Wester, H. J., Herz, M., Becker, I., Kruger, A., et al. (2002). O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes. European Journal of Nuclear Medicine and Molecular Imaging, 29, 1039–1046.

    PubMed  CAS  Google Scholar 

  125. Pauleit, D., Floeth, F., Tellmann, L., Hamacher, K., Hautzel, H., Muller, H. W., et al. (2004). Comparison of O-(2-18F-fluoroethyl)-L-tyrosine PET and 3-123I-iodo-alpha-methyl-L-tyrosine SPECT in brain tumors. Journal of Nuclear Medicine, 45, 374–381.

    PubMed  CAS  Google Scholar 

  126. Weber, W. A., Wester, H. J., Grosu, A. L., Herz, M., Dzewas, B., Feldmann, H. J., et al. (2000). O-(2-[18F]fluoroethyl)-L-tyrosine and L-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study. European Journal of Nuclear Medicine, 27, 542–549.

    PubMed  CAS  Google Scholar 

  127. Popperl, G., Gotz, C., Rachinger, W., Gildehaus, F. J., Tonn, J. C., & Tatsch, K. (2004). Value of O-(2-[18F]fluoroethyl)-L-tyrosine PET for the diagnosis of recurrent glioma. European Journal of Nuclear Medicine and Molecular Imaging, 31, 1464–1470.

    PubMed  Google Scholar 

  128. Rachinger, W., Goetz, C., Popperl, G., Gildehaus, F. J., Kreth, F. W., Holtmannspotter, M., et al. (2005). Positron emission tomography with O-(2-[18F]fluoroethyl)-L-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas. Neurosurgery, 57, 505–511, discussion 505–511.

    PubMed  Google Scholar 

  129. Pauleit, D., Floeth, F., Hamacher, K., Riemenschneider, M. J., Reifenberger, G., Muller, H. W., et al. (2005). O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain, 128, 678–687.

    PubMed  Google Scholar 

  130. Weckesser, M., Langen, K. J., Rickert, C. H., Kloska, S., Straeter, R., Hamacher, K., et al. (2005). O-(2-[18F]fluoroethyl)-L-tyrosine PET in the clinical evaluation of primary brain tumours. European Journal of Nuclear Medicine and Molecular Imaging, 32, 422–429.

    PubMed  CAS  Google Scholar 

  131. Popperl, G., Kreth, F. W., Herms, J., Koch, W., Mehrkens, J. H., Gildehaus, F. J., et al. (2006). Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? Journal of Nuclear Medicine, 47, 393–403.

    PubMed  Google Scholar 

  132. Popperl, G., Kreth, F. W., Mehrkens, J. H., Herms, J., Seelos, K., Koch, W., et al. (2007). FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading. European Journal of Nuclear Medicine and Molecular Imaging, 34, 1933–1942.

    PubMed  Google Scholar 

  133. Floeth, F. W., Pauleit, D., Sabel, M., Reifenberger, G., Stoffels, G., Stummer, W., et al. (2006). 18F-FET PET differentiation of ring-enhancing brain lesions. Journal of Nuclear Medicine, 47, 776–782.

    PubMed  CAS  Google Scholar 

  134. Salber, D., Stoffels, G., Pauleit, D., Oros-Peusquens, A. M., Shah, N. J., Klauth, P., Hamacher, K., Coenen, H. H., & Langen, K. J. (2007). Differential uptake of O-(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3H-deoxyglucose in brain abscesses. Journal of Nuclear Medicine, 48, 2056–2062.

    PubMed  CAS  Google Scholar 

  135. Salber, D., Stoffels, G., Pauleit, D., Reifenberger, G., Sabel, M., Shah, N. J., et al. (2006). Differential uptake of [18F]FET and [3H]-L-methionine in focal cortical ischemia. Nuclear Medicine and Biology, 33, 1029–1035.

    PubMed  CAS  Google Scholar 

  136. Pauleit, D., Stoffels, G., Schaden, W., Hamacher, K., Bauer, D., Tellmann, L., et al. (2005). PET with O-(2-18F-Fluoroethyl)-L-tyrosine in peripheral tumors: first clinical results. Journal of Nuclear Medicine, 46, 411–416.

    PubMed  CAS  Google Scholar 

  137. Pauleit, D., Zimmermann, A., Stoffels, G., Bauer, D., Risse, J., Fluss, M. O., et al. (2006). 18F-FET PET compared with 18F-FDG PET and CT in patients with head and neck cancer. Journal of Nuclear Medicine, 47, 256–261.

    PubMed  Google Scholar 

  138. Luxen, A., Guillaume, M., Melega, W. P., Pike, V. W., Solin, O., & Wagner, R. (1992). Production of 6-[18F]fluoro-L-dopa and its metabolism in vivo—a critical review. International Journal of Radiation Applications and Instrumentation, 19, 149–158.

    CAS  Google Scholar 

  139. Fischman, A. J. (2005). Role of [18F]-dopa-PET imaging in assessing movement disorders. Radiologic Clinics of North America, 43, 93–106.

    PubMed  Google Scholar 

  140. Huang, S. C., Stout, D. B., Yee, R. E., Satyamurthy, N., & Barrio, J. R. (1998). Distribution volume of radiolabeled large neutral amino acids in brain tissue. Journal of Cerebral Blood Flow and Metabolism, 18, 1288–1293.

    PubMed  CAS  Google Scholar 

  141. Stout, D. B., Huang, S. C., Melega, W. P., Raleigh, M. J., Phelps, M. E., & Barrio, J. R. (1998). Effects of large neutral amino acid concentrations on 6-[F-18]Fluoro-L-DOPA kinetics. Journal of Cerebral Blood Flow and Metabolism, 18, 43–51.

    PubMed  CAS  Google Scholar 

  142. Becherer, A., Karanikas, G., Szabo, M., Zettinig, G., Asenbaum, S., Marosi, C., et al. (2003). Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine. European Journal of Nuclear Medicine and Molecular Imaging, 30, 1561–1567.

    PubMed  CAS  Google Scholar 

  143. Chen, W., Silverman, D. H., Delaloye, S., Czernin, J., Kamdar, N., Pope, W., et al. (2006). 18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. Journal of Nuclear Medicine, 47, 904–911.

    PubMed  CAS  Google Scholar 

  144. Schiepers, C., Chen, W., Cloughesy, T., Dahlbom, M., & Huang, S. C. (2007). 18F-FDOPA kinetics in brain tumors. Journal of Nuclear Medicine, 48, 1651–1661.

    PubMed  Google Scholar 

  145. Becherer, A., Szabo, M., Karanikas, G., Wunderbaldinger, P., Angelberger, P., Raderer, M., et al. (2004). Imaging of advanced neuroendocrine tumors with 18F-FDOPA PET. Journal of Nuclear Medicine, 45, 1161–1167.

    PubMed  CAS  Google Scholar 

  146. Hoegerle, S., Altehoefer, C., Ghanem, N., Koehler, G., Waller, C. F., Scheruebl, H., et al. (2001). Whole-body 18F DOPA PET for detection of gastrointestinal carcinoid tumors. Radiology, 220, 373–380.

    PubMed  CAS  Google Scholar 

  147. Koopmans, K. P., de Vries, E. G., Kema, I. P., Elsinga, P. H., Neels, O. C., Sluiter, W. J., et al. (2006). Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. Lancet Oncology, 7, 728–734.

    PubMed  CAS  Google Scholar 

  148. Montravers, F., Grahek, D., Kerrou, K., Ruszniewski, P., de Beco, V., Aide, N., et al. (2006). Can fluorodihydroxyphenylalanine PET replace somatostatin receptor scintigraphy in patients with digestive endocrine tumors? Journal of Nuclear Medicine, 47, 1455–1462.

    PubMed  CAS  Google Scholar 

  149. Sundin, A., Garske, U., & Orlefors, H. (2007). Nuclear imaging of neuroendocrine tumours. Best Practice Research Clinical Endocrinology Metabolism, 21, 69–85.

    PubMed  CAS  Google Scholar 

  150. Jager, P. L., Meijer, W. G., Kema, I. P., Willemse, P. H., Piers, D. A., & de Vries, E. G. (2000). L-3-[123I]Iodo-alpha-methyltyrosine scintigraphy in carcinoid tumors: correlation with biochemical activity and comparison with [111In-DTPA-D-Phe1]-octreotide imaging. Journal of Nuclear Medicine, 41, 1793–1800.

    PubMed  CAS  Google Scholar 

  151. Berlinguet, L., Begin, N., & Babineau, L. M. (1962). Autoradiographic studies of the distribution of 1-aminocyclopentane carboxylic acid in normal and cancerous mice. Canadian Journal of Biochemistry and Physiology, 40, 1111–1114.

    PubMed  CAS  Google Scholar 

  152. Sterling, W. R., Henderson, J. F., Mandel, H. G., & Smith, P. K. (1962). The metabolism of 1-aminocyclopentane-1-carboxylic acid in normal and neoplastic tissues. Biochemical Pharmacology, 11, 135–145.

    PubMed  CAS  Google Scholar 

  153. Berlinguet, L., Begin, N., & Sarkar, N. K. (1962). Mechanism of antitumour action of 1-amino-cyclopentane carboxylic acid. Nature, 194, 1082–1083.

    PubMed  CAS  Google Scholar 

  154. Carter, S. K. (1970). Chemotherapy fact sheet: 1-amino-cyclopentanecarboxylic acid (NSC-1026). Publications Section, Program Analysis Branch, Chemotherapy, National Cancer Institute.

  155. Washburn, L. C., Sun, T. T., Anon, J. B., & Hayes, R. L. (1978). Effect of structure on tumor specificity of alicyclic alpha-amino acids. Cancer Research, 38, 2271–2273.

    PubMed  CAS  Google Scholar 

  156. Hayes, R. L., Washburn, L. C., Wieland, B. W., Sun, T. T., Turtle, R. R., & Butler, T. A. (1976). Carboxyl-labeled 11C-1-aminocyclopentanecarboxylic acid, a potential agent for cancer detection. Journal of Nuclear Medicine, 17, 748–751.

    PubMed  CAS  Google Scholar 

  157. Washburn, L. C., Sun, T. T., Byrd, B., Hayes, R. L., & Butler, T. A. (1979). 1-aminocyclobutane[11C]carboxylic acid, a potential tumor-seeking agent. Journal of Nuclear Medicine, 20, 1055–1061.

    PubMed  CAS  Google Scholar 

  158. Goodman, M., DeVinney, J., Kabalka, G., Ladetsky, M., Hubner, K., Meyer, M., et al. (1991). Microprocessor-controlled open vessel system for the production of no-carrier-added-1-aminocyclobutane-1-carboxylic acid. Journal of Labelled Compounds & Radiopharmaceuticals, 30, 184–186.

    Google Scholar 

  159. Christensen, H. N. (1990). Role of amino acid transport and counter transport in nutrition and metabolism. Physiological Reviews, 70, 43–77.

    PubMed  CAS  Google Scholar 

  160. McConathy, J., Martarello, B., Simpson, N., Simpson, C., Malveaux, E., Yu, W., et al. (2003). Uptake profiles of six 18F-labeled amino acids for tumor imaging: comparison of in vitro and in vivo uptake of branched chain and cyclobutyl amino acids by 9 L gliosarcoma tumor cells. Journal of Nuclear Medicine, 43, 41.

    Google Scholar 

  161. Yu, W., Giamis, A., Kurosaki, F., & Goodman, M. (2006). Syn-[18F]FACBC: A Potential Tumor Imaging Agent. Journal of Nuclear Medicine, 47, 428.

    Google Scholar 

  162. Hubner, K. F., Andrews, G. A., Washburn, L., Wieland, B. W., Gibbs, W. D., Hayes, R. L., et al. (1977). Tumor location with 1-aminocyclopentane [11C] carboxylic acid: preliminary clinical trials with single-photon detection. Journal of Nuclear Medicine, 18, 1215–1221.

    PubMed  CAS  Google Scholar 

  163. Hubner, K. F., Krauss, S., Washburn, L. C., Gibbs, W. D., & Holloway, E. C. (1981). Tumor detection with 1-aminocyclopentane and 1-aminocyclobutane C-11-carboxylic acid using positron emission computerized tomography. Clinical Nuclear Medicine, 6, 249–252.

    PubMed  CAS  Google Scholar 

  164. Hubner, K. F., Thie, J. A., Smith, G. T., Kabalka, G. W., Keller, I. B., Kliefoth, A. B., et al. (1998). Positron emission tomography (PET) with 1-aminocyclobutane-1-[11C]carboxylic acid (1-[11C]-ACBC) for detecting recurrent brain tumors. Clinical Positron Imaging, 1, 165–173.

    PubMed  Google Scholar 

  165. McConathy, J., Voll, R. J., Yu, W., Crowe, R. J., & Goodman, M. M. (2003). Improved synthesis of anti-[18F]FACBC: improved preparation of labeling precursor and automated radiosynthesis. Applied Radiation and Isotopes, 58, 657–666.

    PubMed  CAS  Google Scholar 

  166. Schuster, D., Votaw, J., Halkar, R., McConathy, J., Crowe, R., Olson, J., et al. (2003). Uptake of the synthetic pet amino acid radiotracer 1-amino-3-[18f] fluorocyclobutane-1-carboxylic acid (18F-FACBC) within primary and metastatic brain cancer compared with 18f-fluorodeoxyglucose (18F-FDG). Journal of Nuclear Medicine, 44, 167.

    Google Scholar 

  167. Shoup, T. M., Olson, J., Hoffman, J. M., Votaw, J., Eshima, D., Eshima, L., et al. (1999). Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors. Journal of Nuclear Medicine, 40, 331–338.

    PubMed  CAS  Google Scholar 

  168. Oka, S., Hattori, R., Kurosaki, F., Toyama, M., Williams, L. A., Yu, W., et al. (2007). A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. Journal of Nuclear Medicine, 48, 46–55.

    PubMed  CAS  Google Scholar 

  169. Schuster, D. M., Votaw, J. R., Nieh, P. T., Yu, W., Nye, J. A., Master, V., et al. (2007). Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. Journal of Nuclear Medicine, 48, 56–63.

    PubMed  CAS  Google Scholar 

  170. Nye, J. A., Schuster, D. M., Yu, W., Camp, V. M., Goodman, M. M., & Votaw, J. R. (2007). Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans. Journal of Nuclear Medicine, 48, 1017–1020.

    PubMed  CAS  Google Scholar 

  171. Yu, W., Camp, V., & Goodman, M. (2007). Biological Evaluation of Syn/Anti-[18F]FMACBC for PET Tumor Imaging. Journal of Nuclear Medicine, 48, 342.

    Google Scholar 

  172. Oberdorfer, F., Zobeley, A., Weber, K., Prenant, C., Haberkorn, U., & Maier-Borst, W. (1993). Preparation of [3–11C]aminoisobutyric acid from an azadisilolidine derivative of alanine. Journal of Labelled Compounds & Radiopharmaceuticals, 33, 345–353.

    CAS  Google Scholar 

  173. Schmall, B., Conti, P. S., & Alauddin, M. M. (1996). Synthesis of [11C-methyl]-alpha-aminoisobutyric acid (AIB). Nuclear Medicine and Biology, 23, 263–266.

    PubMed  CAS  Google Scholar 

  174. Schmall, B., Conti, P. S., Bigler, R. E., Zanzonico, P. B., Dahl, J. R., Sundoro-Wu, B. M., et al. (1984). Synthesis and quality assurance of [11C]alpha-aminoisobutyric acid (AIB), a potential radiotracer for imaging and amino acid transport studies in normal and malignant tissues. International Journal of Nuclear Medicine & Biology, 11, 209–214.

    CAS  Google Scholar 

  175. Nagren, K., Sutinen, E., & Jyrkkio, S. (2000). [N-methyl-11C]MeAIB, a tracer for system A amino acid transport: preparation from [11C]methyl triflate and HPLC metabolite analysis of plasma samples after intravenous administration in man. Journal of Labelled Compounds & Radiopharmaceuticals, 43, 1013–1021.

    CAS  Google Scholar 

  176. Prenant, C., Theobald, A., Siegel, T., Joachim, J., Weber, K., Haberkorn, U., et al. (1995). Carbon-11 labelled analogs of alanine by the strecker synthesis. Journal of Labelled Compounds & Radiopharmaceuticals, 36, 579–586.

    CAS  Google Scholar 

  177. Schmall, B., Conti, P. S., Bigler, R. E., Zanzonico, P. B., Reiman, R. E., Benua, R. S., et al. (1987). Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB). Clinical Nuclear Medicine, 12, 22–26.

    PubMed  CAS  Google Scholar 

  178. Sordillo, P. P., DiResta, G. R., Fissekis, J., Conti, P., Benua, R. S., Yeh, S. D., et al. (1991). Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in patients with malignant melanoma. American Journal of Physiologic Imaging, 6, 172–175.

    PubMed  CAS  Google Scholar 

  179. Sutinen, E., Jyrkkio, S., Gronroos, T., Haaparanta, M., Lehikoinen, P., & Nagren, K. (2001). Biodistribution of [11C] methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo. European Journal of Nuclear Medicine, 28, 847–854.

    PubMed  CAS  Google Scholar 

  180. Tolvanen, T., Nagren, K., Yu, M., Sutinen, E., Havu-Auren, K., Jyrkkio, S., et al. (2006). Human radiation dosimetry of [11C]MeAIB, a new tracer for imaging of system A amino acid transport. European Journal of Nuclear Medicine and Molecular Imaging, 33, 1178–1184.

    PubMed  CAS  Google Scholar 

  181. Betz, A. L., & Goldstein, G. W. (1978). Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries. Science, 202, 225–227.

    PubMed  CAS  Google Scholar 

  182. Blasberg, R. G., Fenstermacher, J. D., & Patlak, C. S. (1983). Transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes. Journal of Cerebral Blood Flow and Metabolism, 3, 8–32.

    PubMed  CAS  Google Scholar 

  183. Uehara, H., Miyagawa, T., Tjuvajev, J., Joshi, R., Beattie, B., Oku, T., Finn, R., et al. (1997). Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions. Journal of Cerebral Blood Flow and Metabolism, 17, 1239–1253.

    PubMed  CAS  Google Scholar 

  184. Langen, K. J., Jarosch, M., Hamacher, K., Muhlensiepen, H., Weber, F., Floeth, F., et al. (2004). Imaging of gliomas with Cis-4-[18F]fluoro-L-proline. Nuclear Medicine and Biology, 31, 67–75.

    PubMed  CAS  Google Scholar 

  185. McConathy, J., Martarello, L., Malveaux, E. J., Camp, V. M., Simpson, N. E., Simpson, C. P., et al. (2002). Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid. Journal of Medicinal Chemistry, 45, 2240–2249.

    PubMed  CAS  Google Scholar 

  186. McConathy, J., Martarello, L., Malveaux, E. J., Camp, V. M., Simpson, N. E., Simpson, C. P., et al. (2003). Synthesis and evaluation of 2-amino-4-[18F]fluoro-2-methylbutanoic acid (FAMB): relationship of amino acid transport to tumor imaging properties of branched fluorinated amino acids. Nuclear Medicine and Biology, 30, 477–490.

    PubMed  CAS  Google Scholar 

  187. Bigler, R. E., Zanzonico, P. B., Schmall, B., Conti, P. S., Dahl, J. R., Rothman, L., et al. (1985). Evaluation of [1-11C]-alpha-aminoisobutyric acid for tumor detection and amino acid transport measurement: spontaneous canine tumor studies. European Journal of Nuclear Medicine, 10, 48–55.

    PubMed  CAS  Google Scholar 

  188. Conti, P. S., Sordillo, E. M., Sordillo, P. P., & Schmall, B. (1985). Tumor localization of alpha-aminoisobutyric acid (AIB) in human melanoma heterotransplants. European Journal of Nuclear Medicine, 10, 45–47.

    PubMed  CAS  Google Scholar 

  189. Conti, P. S., Sordillo, P. P., Schmall, B., Benua, R. S., Bading, J. R., Bigler, R. E., et al. (1986). Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma. European Journal of Nuclear Medicine, 12, 353–356.

    PubMed  CAS  Google Scholar 

  190. Gaccioli, F., Huang, C. C., Wang, C., Bevilacqua, E., Franchi-Gazzola, R., Gazzola, G. C., et al. (2006). Amino acid starvation induces the SNAT2 neutral amino acid transporter by a mechanism that involves eukaryotic initiation factor 2alpha phosphorylation and cap-independent translation. Journal of Biological Chemistry, 281, 17929–17940.

    PubMed  Google Scholar 

  191. Sutinen, E., Jyrkkio, S., Alanen, K., Nagren, K., & Minn, H. (2003). Uptake of [N-methyl-11C]alpha-methylaminoisobutyric acid in untreated head and neck cancer studied by PET. European Journal of Nuclear Medicine and Molecular Imaging, 30, 72–77.

    PubMed  CAS  Google Scholar 

  192. Van der Ley, M. (1983). Fluorine-18 labeled aliphatic amino acids. Journal of Labelled Compounds & Radiopharmaceuticals, 20, 453–461.

    Google Scholar 

  193. Wester, H. J., Herz, M., Senekowitsch-Schmidtke, R., Schwaiger, M., Stocklin, G., & Hamacher, K. (1999). Preclinical evaluation of 4-[18F]fluoroprolines: diastereomeric effect on metabolism and uptake in mice. Nuclear Medicine and Biology, 26, 259–265.

    PubMed  CAS  Google Scholar 

  194. Langen, K. J., Muhlensiepen, H., Schmieder, S., Hamacher, K., Broer, S., Borner, A. R., et al. (2002). Transport of cis- and trans-4-[18F]fluoro-L-proline in F98 glioma cells. Nuclear Medicine and Biology, 29, 685–692.

    PubMed  CAS  Google Scholar 

  195. Borner, A. R., Langen, K. J., Herzog, H., Hamacher, K., Muller-Mattheis, V., Schmitz, T., et al. (2001). Whole-body kinetics and dosimetry of cis-4-[18F]fluoro-L-proline. Nuclear Medicine and Biology, 28, 287–292.

    PubMed  CAS  Google Scholar 

  196. Langen, K. J., Borner, A. R., Muller-Mattheis, V., Hamacher, K., Herzog, H., Ackermann, R., et al. (2001). Uptake of cis-4-[18F]fluoro-L-proline in urologic tumors. Journal of Nuclear Medicine, 42, 752–754.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S Kingshighway Blvd, Campus Box 8131, St Louis, MO, USA

    Jonathan McConathy

  2. Department of Radiology, Department of Hematology and Oncology, Emory Center for Positron Emission Tomography, Emory University School of Medicine, 1364 Clifton Road NE, Atlanta, GA, 30322, USA

    Mark M. Goodman

Authors
  1. Jonathan McConathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark M. Goodman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark M. Goodman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McConathy, J., Goodman, M.M. Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography. Cancer Metastasis Rev 27, 555–573 (2008). https://doi.org/10.1007/s10555-008-9154-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-008-9154-7

Keywords

Search

Navigation