Annals of Nuclear Medicine

, Volume 25, Issue 10, pp 717–731 | Cite as

Animal tumor models for PET in drug development

  • Jun ToyoharaEmail author
  • Kiichi Ishiwata
Review article


Positron emission tomography (PET) is being increasingly applied to animal tumor models due to the need for proof-of-concept testing and preclinical efficacy studies of anticancer agents. Regardless of the nature of an experiment, investigators should carefully select a suitable animal tumor model as part of the experimental design. This review introduces sources of information and the guiding principles regarding applicability of various animal tumor models for PET in anticancer agent development especially for small animals.


Animal tumor models Positron emission tomography Drug development Anticancer agent 

List of abbreviations


Anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid




Carcinoembryonic antigen


Epidermal growth factor receptor


Estrogen receptor


Estrogen receptor positive


Estrogen receptor negative


Estrogen responsive element


Fatty acid synthase








Histone deacetylase inhibitors


Human epidermal growth factor receptor 2




Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase


(E)-But-2-enedioic acid [4-(3-[124I]iodoanilino)-quinazolin-6-yl]-amide-(3-morpholin-4-yl-propyl)-amide


Melanocyte-stimulating hormone


Orthotopic prostate cancer transplantation


Positron emission tomography




Tumor viability index


Vascular endothelial growth factor


Vascular endothelial growth factor receptor 2





This work was supported by Grant-in Aid for Scientific Research (B) No. 22390241 from the Japan Society for the Promotion of Science (to Jun Toyohara) and a Grant from the National Center for Global Health and Medicine (to Jun Toyohara, and Kiichi Ishiwata).

Conflict of interest

No other potential conflict of interest relevant to this article was reported.


  1. 1.
    Chen X, Hou Y, Tohme M, Park R, Khankaldyyan V, Gonzales-Gomez I, et al. Pegylated Arg-Gly-Asp peptide: 64Cu labeling and PET imaging of brain tumor αvβ3-integrin expression. J Nucl Med. 2004;45:1776–83.PubMedGoogle Scholar
  2. 2.
    Chen X, Park R, Hou Y, Khankaldyyan V, Gonzales-Gomez I, Tohme M, et al. MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide. Eur J Nucl Med Mol Imaging. 2004;31:1081–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Li ZB, Cai W, Cao Q, Chen K, Wu Z, He L, Chen X, et al. 64Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor αvβ3 integrin expression. J Nucl Med. 2007;48:1162–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Li ZB, Wu Z, Chen K, Chin FT, Chen X. Click chemistry for 18F-labeling of RGD peptides and microPET imaging of tumor integrin αvβ3 expression. Bioconjug Chem. 2007;18:1987–94.PubMedCrossRefGoogle Scholar
  5. 5.
    Li ZB, Chen K, Chen X. 68Ga-labeled multimeric RGD peptides for microPET imaging of integrin αvβ3 expression. Eur J Nucl Med Mol Imaging. 2008;35:1100–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Wu Z, Li ZB, Cai W, He L, Chin FT, Li F, et al. 18F-labeled mini-PEG spacered RGD dimer (18F-FPRGD2): synthesis and microPET imaging of αvβ3 integrin expression. Eur J Nucl Med Mol Imaging. 2007;34:1823–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Haubner R, Weber WA, Beer AJ, Vabuliene E, Reim D, Sarbia M, et al. Noninvasive visualization of the activated αvβ3 integrin in cancer patients by positron emission tomography and [18F]Galacto-RGD. PLoS Med. 2005;2:e70.PubMedCrossRefGoogle Scholar
  8. 8.
    Eiseman JL, Brown-Proctor C, Kinahan PE, Collins JM, Anderson LW, Joseph E, et al. Distribution of 1-(2-deoxy-2-fluoro-β-d-arabinofuranosyl) uracil in mice bearing colorectal cancer xenografts: rationale for therapeutic use and as a positron emission tomography probe for thymidylate synthase. Clin Cancer Res. 2004;10:6669–76.PubMedCrossRefGoogle Scholar
  9. 9.
    Froidevaux S, Calame-Christe M, Schuhmacher J, Tanner H, Saffrich R, Henze M, et al. A gallium-labeled DOTA-α-melanocyte- stimulating hormone analog for PET imaging of melanoma metastases. J Nucl Med. 2004;45:116–23.PubMedGoogle Scholar
  10. 10.
    Sprague JE, Li WP, Liang K, Achilefu S, Anderson CJ. In vitro and in vivo investigation of matrix metalloproteinase expression in metastatic tumor models. Nucl Med Biol. 2006;33:227–37.PubMedCrossRefGoogle Scholar
  11. 11.
    Wang H, Cai W, Chen K, Li ZB, Kashefi A, He L, et al. A new PET tracer specific for vascular endothelial growth factor receptor 2. Eur J Nucl Med Mol Imaging. 2007;34:2001–10.PubMedCrossRefGoogle Scholar
  12. 12.
    Garrison JC, Rold TL, Sieckman GL, Figueroa SD, Volkert WA, Jurisson SS, et al. In vivo evaluation and small-animal PET/CT of a prostate cancer mouse model using 64Cu bombesin analogs: side-by-side comparison of the CB-TE2A and DOTA chelation systems. J Nucl Med. 2007;48:1327–37.PubMedCrossRefGoogle Scholar
  13. 13.
    Pal A, Glekas A, Doubrovin M, Balatoni J, Namavari M, Beresten T, et al. Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small molecular tracer and positron emission tomography. Mol Imaging Biol. 2006;8:262–77.PubMedCrossRefGoogle Scholar
  14. 14.
    Perk LR, Visser GW, Vosjan MJ, Stigter-van Walsum M, Tijink BM, Leemans CR, et al. 89Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals 90Y and 177Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab. J Nucl Med. 2005;46:1898–906.PubMedGoogle Scholar
  15. 15.
    Robinson MK, Doss M, Shaller C, Narayanan D, Marks JD, Adler LP, et al. Quantitative immuno-positron emission tomography imaging of HER2-positive tumor xenografts with an iodine-124 labeled anti-HER2 diabody. Cancer Res. 2005;65:1471–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Cai W, Olafsen T, Zhang X, Cao Q, Gambhir SS, Williams LE, et al. PET imaging of colorectal cancer in xenograft-bearing mice by use of an 18F-labeled T84.66 anti-carcinoembryonic antigen diabody. J Nucl Med. 2007;48:304–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Aliaga A, Rousseau JA, Ouellette R, Cadorette J, van Lier JE, Lecomte R, et al. Breast cancer models to study the expression of estrogen receptors with small animal PET imaging. Nucl Med Biol. 2004;31:761–70.PubMedCrossRefGoogle Scholar
  18. 18.
    Aliaga A, Rousseau JA, Cadorette J, Croteau E, van Lier JE, Lecomte R, et al. A small animal positron emission tomography study of the effect of chemotherapy and hormonal therapy on the uptake of 2-deoxy-2-[F-18]fluoro-d-glucose in murine models of breast cancer. Mol Imaging Biol. 2007;09:144–50.CrossRefGoogle Scholar
  19. 19.
    Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ. Metabolic flare: indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol. 2001;19:2797–803.PubMedGoogle Scholar
  20. 20.
    Ottobrini L, Ciana P, Moresco R, Lecchi M, Belloli S, Martelli C, et al. Development of a bicistronic vector for multimodality imaging of estrogen receptor activity in a breast cancer model: preliminary application. Eur J Nucl Med Mol Imaging. 2008;35:365–78.PubMedCrossRefGoogle Scholar
  21. 21.
    Oyama N, Ponde DE, Dence C, Kim J, Tai YC, Welch MJ. Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. J Nucl Med. 2004;45:519–25.PubMedGoogle Scholar
  22. 22.
    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.PubMedGoogle Scholar
  23. 23.
    Graf N, Herrmann K, den Hollander J, Fend F, Schuster T, Wester HJ, et al. Imaging proliferation to monitor early response of lymphoma to cytotoxic treatment. Mol Imaging Biol. 2008;10:349–55.PubMedCrossRefGoogle Scholar
  24. 24.
    Apisarnthanarax S, Alauddin MM, Mourtada F, Ariga H, Raju U, Mawlawi O, et al. Early detection of chemoradioresponse in esophageal carcinoma by 3′-deoxy-3′-3H-fluorothymidine using preclinical tumor models. Clin Cancer Res. 2006;12:4590–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q, Aboagye EO. Early detection of tumor response to chemotherapy by 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo. Cancer Res. 2005;65:4202–10.PubMedCrossRefGoogle Scholar
  26. 26.
    Buck AK, Kratochwil C, Glatting G, Juweid M, Bommer M, Tepsic D, et al. Early assessment of therapy response in malignant lymphoma with the thymidine analogue [18F]FLT. Eur J Nucl Med Mol Imaging. 2007;34:1775–82.PubMedCrossRefGoogle Scholar
  27. 27.
    Tseng JR, Kang KW, Dandekar M, Yaghoubi S, Lee JH, Christensen JG, et al. Preclinical efficacy of the c-Met inhibitor CE-355621 in a U-87MG mouse xenograft model evaluated by 18F-FDG small-animal PET. J Nucl Med. 2008;49:129–34.PubMedCrossRefGoogle Scholar
  28. 28.
    Assadian S, Aliaga A, Del Maestro RF, Evans AC, Bedell BJ. FDG-PET imaging for the evaluation of antiglioma agents in a rat model. Neuro Oncol. 2008;10:292–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Herranz M, Martin-Caballero J, Fraga MF, Ruiz-Cabello J, Flores JM, Desco M, et al. The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma. Blood. 2006;107:1174–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Lee JS, Orita H, Gabrielson K, Alvey S, Hagemann RL, Kuhajda FP, et al. FDG-PET for pharmacodynamic assessment of the fatty acid synthase inhibitor C75 in an experimental model of lung cancer. Pharm Res. 2007;24:1202–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Kim TJ, Ravoori M, Landen CN, Kamat AA, Han LY, Lu C, et al. Antitumor and antivascular effects of AVE8062 in ovarian carcinoma. Cancer Res. 2007;67:9337–45.PubMedCrossRefGoogle Scholar
  32. 32.
    Cullinane C, Dorow DS, Kansara M, Conus N, Binns D, Hicks RJ, et al. An in vivo tumor model exploiting metabolic response as a biomarker for targeted drug development. Cancer Res. 2005;65:9633–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Hsu AR, Cai W, Veeravagu A, Mohamedali KA, Chen K, Kim S, et al. Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel. J Nucl Med. 2007;48:445–54.PubMedGoogle Scholar
  34. 34.
    Solit DB, Santos E, Pratilas CA, Lobo J, Moroz M, Cai S, et al. 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography is a sensitive method for imaging the response of BRAF-dependent tumors to MEK inhibition. Cancer Res. 2007;67:11463–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Leyton J, Alao JP, Da Costa M, Stavropoulou AV, Latigo JR, Perumal M, et al. In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography. Cancer Res. 2006;66:7621–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC. Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol. 2005;45:495–528.PubMedCrossRefGoogle Scholar
  37. 37.
    Dorow DS, Cullinane C, Conus N, Roselt P, Binns D, McCarthy TJ, et al. Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033. Eur J Nucl Med Mol Imaging. 2006;33:441–52.PubMedCrossRefGoogle Scholar
  38. 38.
    Niu G, Cai W, Chen K, Chen X. Non-invasive PET imaging of EGFR degradation induced by a heat shock protein 90 inhibitor. Mol Imaging Biol. 2008;10:99–106.PubMedCrossRefGoogle Scholar
  39. 39.
    Ishiwata K, Liu HY, Teramoto K, Kawamura K, Oda K, Arii S. Tumor viability evaluation by positron emission tomography with [18F]FDG in the liver metastasis rat model. Ann Nucl Med. 2006;20:463–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Liu HY, Teramoto K, Kawamura K, Oda K, Ishiwata K, Arii S. Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a newly devised index obtained by positron emission tomography with [18F] FDG. J Hepatobiliary Pancreat Surg. 2007;14:276–82.PubMedCrossRefGoogle Scholar
  41. 41.
    Woo SK, Lee TS, Kim KM, Kim JY, Jung JH, Kang JH, et al. Anesthesia condition for 18F-FDG imaging of lung metastasis tumors using small animal PET. Nucl Med Biol. 2008;35:143–50.PubMedCrossRefGoogle Scholar
  42. 42.
    Franzius C, Hotfilder M, Poremba C, Hermann S, Schäfers K, Gabbert HE, et al. Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model. Eur J Nucl Med Mol Imaging. 2006;33:1432–41.PubMedCrossRefGoogle Scholar
  43. 43.
    Hsu WK, Virk MS, Feeley BT, Stout DB, Chatziioannou AF, Lieberman JR. Characterization of osteolytic, osteoblastic, and mixed lesions in a prostate cancer mouse model using 18F-FDG and 18F-fluoride PET/CT. J Nucl Med. 2008;49:414–21.PubMedCrossRefGoogle Scholar
  44. 44.
    Cao Q, Cai W, Niu G, He L, Chen X. Multimodality imaging of IL-18-binding protein-Fc therapy of experimental lung metastasis. Clin Cancer Res. 2008;14:6137–45.PubMedCrossRefGoogle Scholar
  45. 45.
    van Kouwen MC, Laverman P, van Krieken JH, Oyen WJ, Jansen JB, Drenth JP. FDG-PET in the detection of early pancreatic cancer in a BOP hamster model. Nucl Med Biol. 2005;32:445–50.PubMedCrossRefGoogle Scholar
  46. 46.
    van Kouwen MC, Laverman P, van Krieken JH, Oyen WJ, Nagengast FM, Drenth JP. Noninvasive monitoring of colonic carcinogenesis: feasibility of [18F]FDG-PET in the azoxymethane model. Nucl Med Biol. 2006;33:245–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Li Y, Woodall C, Wo JM, Zheng H, Ng CK, Ray MB, et al. The use of dynamic positron emission tomography imaging for evaluating the carcinogenic progression of intestinal metaplasia to esophageal adenocarcinoma. Cancer Invest. 2008;26:278–85.PubMedCrossRefGoogle Scholar
  48. 48.
    Yeh CN, Lin KJ, Hsiao IT, Yen TC, Chen TW, Jan YY, et al. Animal PET for thioacetamide-induced rat cholangiocarcinoma: a novel and reliable platform. Mol Imaging Biol. 2008;10:209–16.PubMedCrossRefGoogle Scholar
  49. 49.
    Bradbury MS, Hambardzumyan D, Zanzonico PB, Schwartz J, Cai S, Burnazi EM, et al. Dynamic small-animal PET imaging of tumor proliferation with 3′-deoxy-3′-18F-fluorothymidine in a genetically engineered mouse model of high-grade gliomas. J Nucl Med. 2008;49:422–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Choi SH, Moon WK, Hong JH, Son KR, Cho N, Kwon BJ, et al. Lymph node metastasis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging versus PET/CT in a rabbit model. Radiology. 2007;242:137–43.PubMedCrossRefGoogle Scholar
  51. 51.
    Park HS, Chung JW, Jae HJ, Kim YI, Son KR, Lee MJ, et al. FDG-PET for evaluating the antitumor effect of intraarterial 3-bromopyruvate administration in a rabbit VX2 liver tumor model. Korean J Radiol. 2007;8:216–24.PubMedCrossRefGoogle Scholar
  52. 52.
    Song SL, Liu JJ, Huang G, Wang ZH, Song YY, Sun XG, et al. Changes in 18F-FDG uptake within minutes after chemotherapy in a rabbit VX2 tumor model. J Nucl Med. 2008;49:303–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Stewart EE, Chen X, Hadway J, Lee TY. Correlation between hepatic tumor blood flow and glucose utilization in a rabbit liver tumor model. Radiology. 2006;239:740–50.PubMedCrossRefGoogle Scholar
  54. 54.
    Buursma AR, Beerens AM, de Vries EF, van Waarde A, Rots MG, Hospers GA, et al. The human norepinephrine transporter in combination with 11C-m-hydroxyephedrine as a reporter gene/reporter probe for PET of gene therapy. J Nucl Med. 2005;46:2068–75.PubMedGoogle Scholar
  55. 55.
    Chen X, Park R, Shahinian AH, Tohme M, Khankaldyyan V, Bozorgzadeh MH, et al. 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis. Nucl Med Biol. 2004;31:179–89.PubMedCrossRefGoogle Scholar
  56. 56.
    Chen X, Park R, Khankaldyyan V, Gonzales-Gomez I, Tohme M, Moats RA, et al. Longitudinal microPET imaging of brain tumor growth with F-18-labeled RGD peptide. Mol Imaging Biol. 2006;8:9–15.PubMedCrossRefGoogle Scholar
  57. 57.
    Israel I, Brandau W, Farmakis G, Samnick S. Improved synthesis of no-carrier-added p-[124I]iodo-l-phenylalanine and p-[131I]iodo-l-phenylalanine for nuclear medicine applications in malignant gliomas. Appl Radiat Isot. 2008;66:513–22.PubMedCrossRefGoogle Scholar
  58. 58.
    Li ZB, Wu Z, Cao Q, Dick DW, Tseng JR, Gambhir SS, et al. The synthesis of 18F-FDS and its potential application in molecular imaging. Mol Imaging Biol. 2008;10:92–8.PubMedCrossRefGoogle Scholar
  59. 59.
    Tian M, Zhang H, Higuchi T, Oriuchi N, Inoue T, Endo K. Effect of mitomycin C and vinblastine on FDG uptake of human nonsmall-cell lung cancer xenografts in nude mice. Cancer Biother Radiopharm. 2004;19:601–5.PubMedGoogle Scholar
  60. 60.
    Bao A, Phillips WT, Goins B, McGuff HS, Zheng X, Woolley FR, et al. Setup and characterization of a human head and neck squamous cell carcinoma xenograft model in nude rats. Otolaryngol Head Neck Surg. 2006;135:853–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Haase C, Bergmann R, Fuechtner F, Hoepping A, Pietzsch J. l-type amino acid transporters LAT1 and LAT4 in cancer: uptake of 3-O-methyl-6-18F-fluoro-l-dopa in human adenocarcinoma and squamous cell carcinoma in vitro and in vivo. J Nucl Med. 2007;48:2063–71.PubMedCrossRefGoogle Scholar
  62. 62.
    Molthoff CF, Klabbers BM, Berkhof J, Felten JT, van Gelder M, Windhorst AD, et al. Monitoring response to radiotherapy in human squamous cell cancer bearing nude mice: comparison of 2′-deoxy-2′-[18F]fluoro-d-glucose (FDG) and 3′-[18F]fluoro-3′-deoxythymidine (FLT). Mol Imaging Biol. 2007;9:340–7.PubMedCrossRefGoogle Scholar
  63. 63.
    O’Donoghue JA, Zanzonico P, Pugachev A, Wen B, Smith-Jones P, Cai S, et al. Assessment of regional tumor hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumor models. Int J Radiat Oncol Biol Phys. 2005;61:1493–502.PubMedCrossRefGoogle Scholar
  64. 64.
    Schütze C, Bergmann R, Yaromina A, Hessel F, Kotzerke J, Steinbach J, et al. Effect of increase of radiation dose on local control relates to pre-treatment FDG uptake in FaDu tumours in nude mice. Radiother Oncol. 2007;83:311–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Cao Q, Li ZB, Chen K, Wu Z, He L, Neamati N, et al. Evaluation of biodistribution and anti-tumor effect of a dimeric RGD peptide–paclitaxel conjugate in mice with breast cancer. Eur J Nucl Med Mol Imaging. 2008;35:1489–98.PubMedCrossRefGoogle Scholar
  66. 66.
    Fei X, Zheng QH, Wang JQ, Stone KL, Martinez TD, Miller KD, et al. Synthesis, biodistribution and micro-PET imaging of radiolabeled antimitotic agent T138067 analogues. Bioorg Med Chem Lett. 2004;14:1247–51.PubMedCrossRefGoogle Scholar
  67. 67.
    Jensen MM, Jorgensen JT, Binderup T, Kjaer A. Tumor volume in subcutaneous mouse xenografts measured by microCT is more accurate and reproducible than determined by 18F-FDG-microPET or external caliper. BMC Med Imaging. 2008;8:16.PubMedCrossRefGoogle Scholar
  68. 68.
    Lee J, Jallo GI, Guarnieri M, Carson BS Sr, Penno MB. A novel brainstem tumor model: guide screw technology with functional, radiological, and histopathological characterization. Neurosurg Focus. 2005;18:E11.PubMedCrossRefGoogle Scholar
  69. 69.
    Nanni C, Di Leo K, Tonelli R, Pettinato C, Rubello D, Spinelli A, et al. FDG small animal PET permits early detection of malignant cells in a xenograft murine model. Eur J Nucl Med Mol Imaging. 2007;34:755–62.PubMedCrossRefGoogle Scholar
  70. 70.
    von Forstner C, Egberts JH, Ammerpohl O, Niedzielska D, Buchert R, Mikecz P, et al. Gene expression patterns and tumor uptake of 18F-FDG, 18F-FLT, and 18F-FEC in PET/MRI of an orthotopic mouse xenotransplantation model of pancreatic cancer. J Nucl Med. 2008;49:1362–70.CrossRefGoogle Scholar
  71. 71.
    Flores JE, McFarland LM, Vanderbilt A, Ogasawara AK, Williams SP. The effects of anesthetic agent and carrier gas on blood glucose and tissue uptake in mice undergoing dynamic FDG-PET imaging: sevoflurane and isoflurane compared in air and in oxygen. Mol Imaging Biol. 2008;10:192–200.PubMedCrossRefGoogle Scholar
  72. 72.
    He F, Deng X, Wen B, Liu Y, Sun X, Xing L, et al. Noninvasive molecular imaging of hypoxia in human xenografts: comparing hypoxia-induced gene expression with endogenous and exogenous hypoxia markers. Cancer Res. 2008;68:8597–606.PubMedCrossRefGoogle Scholar
  73. 73.
    Kok PJ, van Eerd JE, Boerman OC, Corstens FH, Oyen WJ. Biodistribution and imaging of FDG in rats with LS174T carcinoma xenografts and focal Escherichia coli infection. Cancer Biother Radiopharm. 2005;20:310–5.PubMedCrossRefGoogle Scholar
  74. 74.
    Leyton J, Smith G, Lees M, Perumal M, Nguyen QD, Aigbirhio FI, et al. Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Mol Cancer Ther. 2008;7:3112–21.PubMedCrossRefGoogle Scholar
  75. 75.
    Wuest F, Kniess T, Bergmann R, Pietzsch J. Synthesis and evaluation in vitro and in vivo of a 11C-labeled cyclooxygenase-2 (COX-2) inhibitor. Bioorg Med Chem. 2008;16:7662–70.PubMedCrossRefGoogle Scholar
  76. 76.
    Brouwers A, Verel I, Van Eerd J, Visser G, Steffens M, Oosterwijk E, et al. PET radioimmunoscintigraphy of renal cell cancer using 89Zr-labeled cG250 monoclonal antibody in nude rats. Cancer Biother Radiopharm. 2004;19:155–63.PubMedCrossRefGoogle Scholar
  77. 77.
    Cheng Z, De Jesus OP, Namavari M, De A, Levi J, Webster JM, et al. Small-animal PET imaging of human epidermal growth factor receptor type 2 expression with site-specific 18F-labeled protein scaffold molecules. J Nucl Med. 2008;49:804–13.PubMedCrossRefGoogle Scholar
  78. 78.
    Sugiyama M, Sakahara H, Sato K, Harada N, Fukumoto D, Kakiuchi T, et al. Evaluation of 3′-deoxy-3′-18F-fluorothymidine for monitoring tumor response to radiotherapy and photodynamic therapy in mice. J Nucl Med. 2004;45:1754–8.PubMedGoogle Scholar
  79. 79.
    Authier S, Tremblay S, Dumulon V, Dubuc C, Ouellet R, Lecomte R, et al. [11C] acetoacetate utilization by breast and prostate tumors: a PET and biodistribution study in mice. Mol Imaging Biol. 2008;10:217–23.PubMedCrossRefGoogle Scholar
  80. 80.
    Yang YS, Zhang X, Xiong Z, Chen X. Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma. Nucl Med Biol. 2006;33:371–80.PubMedCrossRefGoogle Scholar
  81. 81.
    Reischl G, Dorow DS, Cullinane C, Katsifis A, Roselt P, Binns D, et al. Imaging of tumor hypoxia with [124I]IAZA in comparison with [18F]FMISO and [18F]FAZA-first small animal PET results. J Pharm Pharm Sci. 2007;10:203–11.PubMedGoogle Scholar
  82. 82.
    Hajitou A, Lev DC, Hannay JA, Korchin B, Staquicini FI, Soghomonyan S, et al. A preclinical model for predicting drug response in soft-tissue sarcoma with targeted AAVP molecular imaging. Proc Natl Acad Sci USA. 2008;105:4471–6.PubMedCrossRefGoogle Scholar
  83. 83.
    Matsumoto K, Szajek L, Krishna MC, Cook JA, Seidel J, Grimes K, et al. The influence of tumor oxygenation on hypoxia imaging in murine squamous cell carcinoma using [64Cu]Cu-ATSM or [18F]Fluoromisonidazole positron emission tomography. Int J Oncol. 2007;30:873–81.PubMedGoogle Scholar
  84. 84.
    Yapp DT, Woo J, Kartono A, Sy J, Oliver T, Skov KA, et al. Non-invasive evaluation of tumour hypoxia in the Shionogi tumour model for prostate cancer with 18F-EF5 and positron emission tomography. BJU Int. 2007;99:1154–60.PubMedCrossRefGoogle Scholar
  85. 85.
    Pan MH, Huang SC, Liao YP, Schaue D, Wang CC, Stout DB, et al. FLT-PET imaging of radiation responses in murine tumors. Mol Imaging Biol. 2008;10:325–34.PubMedCrossRefGoogle Scholar
  86. 86.
    Kim SJ, Lee JS, Im KC, Kim SY, Park SA, Lee SJ, et al. Kinetic modeling of 3′-deoxy-3′-18F-fluorothymidine for quantitative cell proliferation imaging in subcutaneous tumor models in mice. J Nucl Med. 2008;49:2057–66.PubMedCrossRefGoogle Scholar
  87. 87.
    Dobrenkov K, Olszewska M, Likar Y, Shenker L, Gunset G, Cai S, et al. Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging. J Nucl Med. 2008;49:1162–70.PubMedCrossRefGoogle Scholar
  88. 88.
    McQuade P, Miao Y, Yoo J, Quinn TP, Welch MJ, Lewis JS. Imaging of melanoma using 64Cu- and 86Y-DOTA-ReCCMSH(Arg11), a cyclized peptide analogue of α-MSH. J Med Chem. 2005;48:2985–92.PubMedCrossRefGoogle Scholar
  89. 89.
    Chaise C, Itti E, Petegnief Y, Wirquin E, Copie-Bergman C, Farcet JP, et al. [F-18]-Fluoro-2-deoxy-d-glucose positron emission tomography as a tool for early detection of immunotherapy response in a murine B cell lymphoma model. Cancer Immunol Immunother. 2007;56:1163–71.PubMedCrossRefGoogle Scholar
  90. 90.
    Christian N, Bol A, De Bast M, Labar D, Lee J, Mahy P, et al. Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model. Eur J Nucl Med Mol Imaging. 2007;34:1348–54.PubMedCrossRefGoogle Scholar
  91. 91.
    Chen JC, Chang SM, Hsu FY, Wang HE, Liu RS. MicroPET-based pharmacokinetic analysis of the radiolabeled boron compound [18F]FBPA-F in rats with F98 glioma. Appl Radiat Isot. 2004;61:887–91.PubMedCrossRefGoogle Scholar
  92. 92.
    Hsieh CH, Chen YF, Chen FD, Hwang JJ, Chen JC, Liu RS, et al. Evaluation of pharmacokinetics of 4-borono-2-18F-fluoro-l-phenylalanine for boron neutron capture therapy in a glioma-bearing rat model with hyperosmolar blood-brain barrier disruption. J Nucl Med. 2005;46:1858–65.PubMedGoogle Scholar
  93. 93.
    Wang HE, Liao AH, Deng WP, Chang PF, Chen JC, Chen FD, et al. Evaluation of 4-borono-2-18F-fluoro-l-phenylalanine-fructose as a probe for boron neutron capture therapy in a glioma-bearing rat model. J Nucl Med. 2004;45:302–8.PubMedGoogle Scholar
  94. 94.
    Wang HE, Wu SY, Chang CW, Liu RS, Hwang LC, Lee TW, et al. Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model. Nucl Med Biol. 2005;32:367–75.PubMedCrossRefGoogle Scholar
  95. 95.
    Buursma AR, van Dillen IJ, van Waarde A, Vaalburg W, Hospers GA, Mulder NH, et al. Monitoring HSVtk suicide gene therapy: the role of [18F]FHPG membrane transport. Br J Cancer. 2004;91:2079–85.PubMedCrossRefGoogle Scholar
  96. 96.
    van Waarde A, Cobben DC, Suurmeijer AJ, Maas B, Vaalburg W, de Vries EF, et al. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med. 2004;45:695–700.PubMedGoogle Scholar
  97. 97.
    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.PubMedGoogle Scholar
  98. 98.
    Dence CS, Ponde DE, Welch MJ, Lewis JS. Autoradiographic and small-animal PET comparisons between 18F-FMISO, 18F-FDG, 18F-FLT and the hypoxic selective 64Cu-ATSM in a rodent model of cancer. Nucl Med Biol. 2008;35:713–20.PubMedCrossRefGoogle Scholar
  99. 99.
    Miletic H, Fischer YH, Giroglou T, Rueger MA, Winkeler A, Li H, et al. Normal brain cells contribute to the bystander effect in suicide gene therapy of malignant glioma. Clin Cancer Res. 2007;13:6761–8.PubMedCrossRefGoogle Scholar
  100. 100.
    Kunz P, Hoffend J, Altmann A, Dimitrakopoulou-Strauss A, Koczan D, Eisenhut M, et al. Angiopoietin-2 overexpression in morris hepatoma results in increased tumor perfusion and induction of critical angiogenesis-promoting genes. J Nucl Med. 2006;47:1515–24.PubMedGoogle Scholar
  101. 101.
    Kubota K, Furumoto S, Iwata R, Fukuda H, Kawamura K, Ishiwata K. Comparison of 18F-fluoromethylcholine and 2-deoxy-d-glucose in the distribution of tumor and inflammation. Ann Nucl Med. 2006;20:527–33.PubMedCrossRefGoogle Scholar
  102. 102.
    Zhao S, Kuge Y, Kohanawa M, Takahashi T, Kawashima H, Temma T, et al. Extensive FDG uptake and its modification with corticosteroid in a granuloma rat model: an experimental study for differentiating granuloma from tumors. Eur J Nucl Med Mol Imaging. 2007;34:2096–105.PubMedCrossRefGoogle Scholar
  103. 103.
    Dubois L, Landuyt W, Haustermans K, Dupont P, Bormans G, Vermaelen P, et al. Evaluation of hypoxia in an experimental rat tumour model by [18F]fluoromisonidazole PET and immunohistochemistry. Br J Cancer. 2004;91:1947–54.PubMedCrossRefGoogle Scholar
  104. 104.
    Dutour A, Monteil J, Paraf F, Charissoux JL, Kaletta C, Sauer B, et al. Endostatin cDNA/cationic liposome complexes as a promising therapy to prevent lung metastases in osteosarcoma: study in a human-like rat orthotopic tumor. Mol Ther. 2005;11:311–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Bayly SR, King RC, Honess DJ, Barnard PJ, Betts HM, Holland JP, et al. In vitro and in vivo evaluations of a hydrophilic 64Cu-bis(thiosemicarbazonato)-glucose conjugate for hypoxia imaging. J Nucl Med. 2008;49:1862–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Raffel DM, Jung YW, Gildersleeve DL, Sherman PS, Moskwa JJ, Tluczek LJ, et al. Radiolabeled phenethylguanidines: novel imaging agents for cardiac sympathetic neurons and adrenergic tumors. J Med Chem. 2007;50:2078–88.PubMedCrossRefGoogle Scholar
  107. 107.
    Hamazawa Y, Koyama K, Okamura T, Wada Y, Wakasa T, Okuma T, et al. Comparison of dynamic FDG-microPET study in a rabbit turpentine-induced inflammatory model and in a rabbit VX2 tumor model. Ann Nucl Med. 2007;21:47–55.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2011

Authors and Affiliations

  1. 1.Positron Medical CenterTokyo Metropolitan Institute of GerontologyTokyoJapan

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