Abstract
Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography (PET) has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with non-invasive procedures. In particular, PET imaging takes advantage of traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of cancer. 18F-fluorodeoxyglucose (18F-FDG), the only FDA approved oncological PET tracer, has been widely utilized in cancer diagnosis, staging, restaging, and even monitoring response to therapy; however, 18F-FDG is not a tumor-specific PET tracer. Over the last decade, many promising tumor-specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current non-18F-FDG PET tracers in oncology that have been developed based on tumor characteristics such as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and tumor-specific antigens and surface receptors.
Similar content being viewed by others
References
Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology. 2004;231:305–32.
Reske SN, Kotzerke J. FDG-PET for clinical use. Results of the 3rd German Interdisciplinary Consensus Conference, "Onko-PET III", 21 July and 19 September 2000. Eur J Nucl Med. 2001;28:1707–23.
Miller JC, Fischman AJ, Aquino SL, Blake MA, Thrall JH, Lee SI. FDG-PET CT for tumor imaging. J Am Coll Radiol. 2007;4:256–9.
Jimenez-Requena F, Delgado-Bolton RC, Fernandez-Perez C, Gambhir SS, Schwimmer J, Perez-Vazquez JM, et al. Meta-analysis of the performance of 18F-FDG PET in cutaneous melanoma. Eur J Nucl Med Mol Imaging. 2010;37:284–300.
Tatsumi M, Cohade C, Bristow RE, Wahl RL. Imaging uterine cervical cancer with FDG-PET/CT: direct comparison with PET. Mol Imaging Biol. 2009;11:229–35.
Escalona S, Blasco JA, Reza MM, Andradas E, Gomez N. A systematic review of FDG-PET in breast cancer. Med Oncol. 2010;27:114–29.
Stokkel MP, Duchateau CS, Dragoiescu C. The value of FDG-PET in the follow-up of differentiated thyroid cancer: a review of the literature. Q J Nucl Med Mol Imaging. 2006;50:78–87.
De Geus-Oei LF, Ruers TJ, Punt CJ, Leer JW, Corstens FH, Oyen WJ. FDG-PET in colorectal cancer. Cancer Imaging. 2006;6:S71–81.
Evans KD, Tulloss TA, Hall N. 18FDG uptake in brown fat: potential for false positives. Radiol Technol. 2007;78:361–6.
Okuma T, Matsuoka T, Okamura T, Wada Y, Yamamoto A, Oyama Y, et al. 18F-FDG small-animal PET for monitoring the therapeutic effect of CT-guided radiofrequency ablation on implanted VX2 lung tumors in rabbits. J Nucl Med. 2006;47:1351–8.
Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev. 1990;70:43–77.
Singhal T, Narayanan TK, Jain V, Mukherjee J, Mantil J. 11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas. Mol Imaging Biol. 2008;10:1–18.
Leskinen-Kallio S, Nagren K, Lehikoinen P, Ruotsalainen U, Teras M, Joensuu H. Carbon-11-methionine and PET is an effective method to image head and neck cancer. J Nucl Med. 1992;33:691–5.
Inoue T, Kim EE, Wong FC, Yang DJ, Bassa P, Wong WH, et al. Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors. J Nucl Med. 1996;37:1472–6.
Becherer A, Karanikas G, Szabo M, Zettinig G, Asenbaum S, Marosi C, et al. Brain tumour imaging with PET: a comparison between [18F]fluorodopa and [11C]methionine. Eur J Nucl Med Mol Imaging. 2003;30:1561–7.
Lindholm P, Leskinen S, Nagren K, Lehikoinen P, Ruotsalainen U, Teras M, et al. Carbon-11-methionine PET imaging of malignant melanoma. J Nucl Med. 1995;36:1806–10.
Couturier O, Luxen A, Chatal JF, Vuillez JP, Rigo P, Hustinx R. Fluorinated tracers for imaging cancer with positron emission tomography. Eur J Nucl Med Mol Imaging. 2004;31:1182–206.
Laverman P, Boerman OC, Corstens FH, Oyen WJ. Fluorinated amino acids for tumour imaging with positron emission tomography. Eur J Nucl Med Mol Imaging. 2002;29:681–90.
McConathy J, Goodman MM. Non-natural amino acids for tumor imaging using positron emission tomography and single photon emission computed tomography. Cancer Metastasis Rev. 2008;27:555–73.
Popperl G, Kreth FW, Herms J, Koch W, Mehrkens JH, Gildehaus FJ, et al. Analysis of 18F-FET PET for grading of recurrent gliomas: is evaluation of uptake kinetics superior to standard methods? J Nucl Med. 2006;47:393–403.
Thiele F, Ehmer J, Piroth MD, Eble MJ, Coenen HH, Kaiser HJ, et al. The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma. Phys Med Biol. 2009;54:5525–39.
Stadlbauer A, Prante O, Nimsky C, Salomonowitz E, Buchfelder M, Kuwert T, et al. Metabolic imaging of cerebral gliomas: spatial correlation of changes in O-(2-18F-fluoroethyl)-L-tyrosine PET and proton magnetic resonance spectroscopic imaging. J Nucl Med. 2008;49:721–9.
Stadlbauer A, Polking E, Prante O, Nimsky C, Buchfelder M, Kuwert T, et al. Detection of tumour invasion into the pyramidal tract in glioma patients with sensorimotor deficits by correlation of 18F-fluoroethyl-L: -tyrosine PET and magnetic resonance diffusion tensor imaging. Acta Neurochir (Wien). 2009;151:1061–9.
Tripathi M, Sharma R, D'Souza M, Jaimini A, Panwar P, Varshney R, et al. Comparative evaluation of F-18 FDOPA, F-18 FDG, and F-18 FLT-PET/CT for metabolic imaging of low grade gliomas. Clin Nucl Med. 2009;34:878–83.
Talbot JN, Kerrou K, Montravers F, Nataf V, Chevalme Y. FDOPA PET has clinical utility in brain tumour imaging: a proposal for a revision of the recent EANM guidelines. Eur J Nucl Med Mol Imaging. 2007;34:1131–2. author reply 1133-4.
Chen W, Silverman DH, Delaloye S, Czernin J, Kamdar N, Pope W, et al. 18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. J Nucl Med. 2006;47:904–11.
Schiepers C, Chen W, Cloughesy T, Dahlbom M, Huang SC. 18F-FDOPA kinetics in brain tumors. J Nucl Med. 2007;48:1651–61.
Koopmans KP, De Vries EG, Kema IP, Elsinga PH, Neels OC, Sluiter WJ, et al. Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. Lancet Oncol. 2006;7:728–34.
Shoup TM, Olson J, Hoffman JM, Votaw J, Eshima D, Eshima L, et al. Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors. J Nucl Med. 1999;40:331–8.
Schuster DM, Votaw JR, Nieh PT, Yu W, Nye JA, Master V, et al. Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med. 2007;48:56–63.
Schuster DM, Nye JA, Nieh PT, Votaw JR, Halkar RK, Issa MM, et al. Initial experience with the radiotracer anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-[ 18F]FACBC) with PET in renal carcinoma. Mol Imaging Biol. 2009;11:434–8.
Nye JA, Schuster DM, Yu W, Camp VM, Goodman MM, Votaw JR. Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans. J Nucl Med. 2007;48:1017–20.
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.
Hara T, Kosaka N, Kishi H. Development of 18F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med. 2002;43:187–99.
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.
Kwee SA, Coel MN, Ly BH, Lim J. 18F-choline PET/CT imaging of RECIST measurable lesions in hormone refractory prostate cancer. Ann Nucl Med. 2009;23:541–8.
Luboldt W, Kufer R, Blumstein N, Toussaint TL, Kluge A, Seemann MD, et al. Prostate carcinoma: diffusion-weighted imaging as potential alternative to conventional MR and 11C-choline PET/CT for detection of bone metastases. Radiology. 2008;249:1017–25.
Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med. 1998;39:990–5.
Huang Z, Zuo C, Guan Y, Zhang Z, Liu P, Xue F, et al. Misdiagnoses of 11C-choline combined with 18F-FDG PET imaging in brain tumours. Nucl Med Commun. 2008;29:354–8.
Hara T, Kosaka N, Shinoura N, Kondo T. PET imaging of brain tumor with [methyl-11C]choline. J Nucl Med. 1997;38:842–7.
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.
Kwee SA, DeGrado TR, Talbot JN, Gutman F, Coel MN. Cancer imaging with fluorine-18-labeled choline derivatives. Semin Nucl Med. 2007;37:420–8.
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;12:98–107.
Kwee SA, Ko JP, Jiang CS, Watters MR, Coel MN. Solitary brain lesions enhancing at MR imaging: evaluation with fluorine 18 fluorocholine PET. Radiology. 2007;244:557–65.
Talbot JN, Fartoux L, Balogova S, Nataf V, Kerrou K, Gutman F, et al. Detection of hepatocellular carcinoma with PET/CT: a prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. J Nucl Med. 2010;51:1699–706.
Wells P, Gunn RN, Alison M, Steel C, Golding M, Ranicar AS, et al. Assessment of proliferation in vivo using 2-[11C]thymidine positron emission tomography in advanced intra-abdominal malignancies. Cancer Res. 2002;62:5698–702.
Mankoff DA, Shields AF, Krohn KA. PET imaging of cellular proliferation. Radiol Clin North Am. 2005;43:153–67.
Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med. 1998;4:1334–6.
Schiepers C, Chen W, Dahlbom M, Cloughesy T, Hoh CK, Huang SC. 18F-fluorothymidine kinetics of malignant brain tumors. Eur J Nucl Med Mol Imaging. 2007;34:1003–11.
Yamamoto Y, Kameyama R, Izuishi K, Takebayashi R, Hagiike M, Asakura M, et al. Detection of colorectal cancer using 18F-FLT PET: comparison with 18F-FDG PET. Nucl Med Commun. 2009;30:841–5.
Yamamoto Y, Nishiyama Y, Kimura N, Ishikawa S, Okuda M, Bandoh S, et al. Comparison of 18F-FLT PET and 18F-FDG PET for preoperative staging in non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2008;35:236–45.
Van Westreenen HL, Cobben DC, Jager PL, Van Dullemen HM, Wesseling J, Elsinga PH, et al. Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer. J Nucl Med. 2005;46:400–4.
Direcks WG, Berndsen SC, Proost N, Peters GJ, Balzarini J, Spreeuwenberg MD, et al. [18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study. Br J Cancer. 2008;99:481–7.
Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3'-[F-18]fluoro-3'-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol. 2006;8:36–42.
Buck AK, Bommer M, Stilgenbauer S, Juweid M, Glatting G, Schirrmeister H, et al. Molecular imaging of proliferation in malignant lymphoma. Cancer Res. 2006;66:11055–61.
Tehrani OS, Douglas KA, Lawhorn-Crews JM, Shields AF. Tracking cellular stress with labeled FMAU reflects changes in mitochondrial TK2. Eur J Nucl Med Mol Imaging. 2008;35:1480–8.
Sun H, Mangner TJ, Collins JM, Muzik O, Douglas K, Shields AF. Imaging DNA synthesis in vivo with 18F-FMAU and PET. J Nucl Med. 2005;46:292–6.
Sun H, Sloan A, Mangner TJ, Vaishampayan U, Muzik O, Collins JM, et al. Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer. Eur J Nucl Med Mol Imaging. 2005;32:15–22.
Laking GR, Price PM. Positron emission tomographic imaging of angiogenesis and vascular function. Br J Radiol 76 Spec No. 2003;1:S50–9.
Niu G, Chen X. PET imaging of angiogenesis. PET Clin. 2009;4:17–38.
Jin H, Varner J. Integrins: roles in cancer development and as treatment targets. Br J Cancer. 2004;90:561–5.
Liu S. Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem. 2009;20:2199–213.
Chen X, Tohme M, Park R, Hou Y, Bading JR, Conti PS. Micro-PET imaging of alphavbeta3-integrin expression with 18F-labeled dimeric RGD peptide. Mol Imaging. 2004;3:96–104.
Wu Z, Li ZB, Chen K, Cai W, He L, Chin FT, et al. microPET of tumor integrin alphavbeta3 expression using 18F-labeled PEGylated tetrameric RGD peptide (18F-FPRGD4). J Nucl Med. 2007;48:1536–44.
Li ZB, Cai W, Cao Q, Chen K, Wu Z, He L, et al. 64Cu-labeled tetrameric and octameric RGD peptides for small-animal PET of tumor alpha(v)beta(3) integrin expression. J Nucl Med. 2007;48:1162–71.
Liu Z, Niu G, Shi J, Liu S, Wang F, Chen X. 68Ga-labeled cyclic RGD dimers with Gly3 and PEG4 linkers: promising agents for tumor integrin alphavbeta3 PET imaging. Eur J Nucl Med Mol Imaging. 2009;36:947–57.
Jeong JM, Hong MK, Chang YS, Lee YS, Kim YJ, Cheon GJ, et al. Preparation of a promising angiogenesis PET imaging agent: 68Ga-labeled c(RGDyK)-isothiocyanatobenzyl-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid and feasibility studies in mice. J Nucl Med. 2008;49:830–6.
Liu S, Liu Z, Chen K, Yan Y, Watzlowik P, Wester HJ, et al. 18F-Labeled galacto and PEGylated RGD dimers for PET Imaging of alpha(v)beta 3 integrin expression. Mol Imaging Biol. 2010;12:530–8.
Cai W, Zhang X, Wu Y, Chen X. A thiol-reactive 18F-labeling agent, N-[2-(4-18F-fluorobenzamido)ethyl]maleimide, and synthesis of RGD peptide-based tracer for PET imaging of alpha v beta 3 integrin expression. J Nucl Med. 2006;47:1172–80.
Beer AJ, Haubner R, Wolf I, Goebel M, Luderschmidt S, Niemeyer M, et al. PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha v beta3 expression. J Nucl Med. 2006;47:763–9.
Pichler BJ, Kneilling M, Haubner R, Braumuller H, Schwaiger M, Rocken M, et al. Imaging of delayed-type hypersensitivity reaction by PET and 18F-galacto-RGD. J Nucl Med. 2005;46:184–9.
Beer AJ, Haubner R, Goebel M, Luderschmidt S, Spilker ME, Wester HJ, et al. Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. J Nucl Med. 2005;46:1333–41.
Haubner R, Wester HJ, Weber WA, Mang C, Ziegler SI, Goodman SL, et al. Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res. 2001;61:1781–5.
Willmann JK, Kimura RH, Deshpande N, Lutz AM, Cochran JR, Gambhir SS. Targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with contrast microbubbles conjugated to integrin-binding knottin peptides. J Nucl Med. 2010;51:433–40.
Kimura RH, Miao Z, Cheng Z, Gambhir SS, Cochran JR. A dual-labeled knottin peptide for PET and near-infrared fluorescence imaging of integrin expression in living subjects. Bioconjug Chem. 2010;21:436–44.
Miao Z, Ren G, Liu H, Kimura RH, Jiang L, Cochran JR, et al. An engineered knottin peptide labeled with 18F for PET imaging of integrin expression. Bioconjug Chem. 2009;20:2342–7.
Kimura RH, Cheng Z, Gambhir SS, Cochran JR. Engineered knottin peptides: a new class of agents for imaging integrin expression in living subjects. Cancer Res. 2009;69:2435–42.
Nayak TK, Garmestani K, Baidoo KE, Milenic DE, Brechbiel MW. PET imaging of tumor angiogenesis in mice with VEGF-A targeted 86Y-CHX-A''-DTPA-bevacizumab. Int J Cancer. 2010;128:920–6.
Stollman TH, Scheer MG, Leenders WP, Verrijp KC, Soede AC, Oyen WJ, et al. Specific imaging of VEGF-A expression with radiolabeled anti-VEGF monoclonal antibody. Int J Cancer. 2008;122:2310–4.
Nagengast WB, De Vries EG, Hospers GA, Mulder NH, De Jong JR, Hollema H, et al. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med. 2007;48:1313–9.
Chen K, Cai W, Li ZB, Wang H, Chen X. Quantitative PET imaging of VEGF receptor expression. Mol Imaging Biol. 2009;11:15–22.
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.
Reddy SB, Williamson SK. Tirapazamine: a novel agent targeting hypoxic tumor cells. Expert Opin Investig Drugs. 2009;18:77–87.
Serganova I, Humm J, Ling C, Blasberg R. Tumor hypoxia imaging. Clin Cancer Res. 2006;12:5260–4.
Padhani A. PET imaging of tumour hypoxia. Cancer Imaging. 2006;6:S117–21.
Koch CJ, Evans SM. Non-invasive PET and SPECT imaging of tissue hypoxia using isotopically labeled 2-nitroimidazoles. Adv Exp Med Biol. 2003;510:285–92.
Lewis JS, Welch MJ. PET imaging of hypoxia. Q J Nucl Med. 2001;45:183–8.
Mees G, Dierckx R, Vangestel C, Van de Wiele C. Molecular imaging of hypoxia with radiolabelled agents. Eur J Nucl Med Mol Imaging. 2009;36:1674–86.
Kizaka-Kondoh S, Konse-Nagasawa H. Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia. Cancer Sci. 2009;100:1366–73.
Cherk MH, Foo SS, Poon AM, Knight SR, Murone C, Papenfuss AT, et al. Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-fluoromisonidazole and 18F-FDG PET. J Nucl Med. 2006;47:1921–6.
Rajendran JG, Wilson DC, Conrad EU, Peterson LM, Bruckner JD, Rasey JS, et al. [18F]FMISO and [18F]FDG PET imaging in soft tissue sarcomas: correlation of hypoxia, metabolism and VEGF expression. Eur J Nucl Med Mol Imaging. 2003;30:695–704.
Rasey JS, Koh WJ, Evans ML, Peterson LM, Lewellen TK, Graham MM, et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys. 1996;36:417–28.
Rischin D, Hicks RJ, Fisher R, Binns D, Corry J, Porceddu S, et al. Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of trans-tasman radiation oncology group study 98.02. J Clin Oncol. 2006;24:2098–104.
Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, et al. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med. 2005;46:106–13.
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.
Grosu AL, Souvatzoglou M, Roper B, Dobritz M, Wiedenmann N, Jacob V, et al. Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. Int J Radiat Oncol Biol Phys. 2007;69:541–51.
Lehtio K, Eskola O, Viljanen T, Oikonen V, Gronroos T, Sillanmaki L, et al. Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004;59:971–82.
Komar G, Seppanen M, Eskola O, Lindholm P, Gronroos TJ, Forsback S, et al. 18F-EF5: a new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med. 2008;49:1944–51.
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.
Allemann K, Wyss MT, Wergin M, Ohlerth S, Rohrer-Bley C, Evans SM, et al. Measurements of hypoxia ([18F]-FMISO, [18F]-EF5) with positron emission tomography (PET) and perfusion using PET ([15O]-H2O) and power Doppler ultrasonography in feline fibrosarcomas. Vet Comp Oncol. 2005;3:211–21.
Ziemer LS, Evans SM, Kachur AV, Shuman AL, Cardi CA, Jenkins WT, et al. Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5. Eur J Nucl Med Mol Imaging. 2003;30:259–66.
Dolbier Jr WR, Li AR, Koch CJ, Shiue CY, Kachur AV. [18F]-EF5, a marker for PET detection of hypoxia: synthesis of precursor and a new fluorination procedure. Appl Radiat Isot. 2001;54:73–80.
van Loon J, Janssen MH, Ollers M, Aerts HJ, Dubois L, Hochstenbag M, et al. PET imaging of hypoxia using [18F]HX4: a phase I trial. Eur J Nucl Med Mol Imaging. 2010;37:1663–8.
Doss M, Zhang JJ, Belanger MJ, Stubbs JB, Hostetler ED, Alpaugh K, et al. Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT. Nucl Med Commun. 2010;31:1016–24.
Dehdashti F, Mintun MA, Lewis JS, Bradley J, Govindan R, Laforest R, et al. In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM. Eur J Nucl Med Mol Imaging. 2003;30:844–50.
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.
Lewis JS, Laforest R, Dehdashti F, Grigsby PW, Welch MJ, Siegel BA. An imaging comparison of 64Cu-ATSM and 60Cu-ATSM in cancer of the uterine cervix. J Nucl Med. 2008;49:1177–82.
Grierson JR, Yagle KJ, Eary JF, Tait JF, Gibson DF, Lewellen B, et al. Production of [F-18]fluoroannexin for imaging apoptosis with PET. Bioconjug Chem. 2004;15:373–9.
Murakami Y, Takamatsu H, Taki J, Tatsumi M, Noda A, Ichise R, et al. 18F-labelled annexin V: a PET tracer for apoptosis imaging. Eur J Nucl Med Mol Imaging. 2004;31:469–74.
Yagle KJ, Eary JF, Tait JF, Grierson JR, Link JM, Lewellen B, et al. Evaluation of 18F-annexin V as a PET imaging agent in an animal model of apoptosis. J Nucl Med. 2005;46:658–66.
Keen HG, Dekker BA, Disley L, Hastings D, Lyons S, Reader AJ, et al. Imaging apoptosis in vivo using 124I-annexin V and PET. Nucl Med Biol. 2005;32:395–402.
Cauchon N, Langlois R, Rousseau JA, Tessier G, Cadorette J, Lecomte R, et al. PET imaging of apoptosis with 64Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V. Eur J Nucl Med Mol Imaging. 2007;34:247–58.
Chu W, Zhang J, Zeng C, Rothfuss J, Tu Z, Chu Y, et al. N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis, in vitro activity, and molecular modeling studies. J Med Chem. 2005;48:7637–47.
Kopka K, Faust A, Keul P, Wagner S, Breyholz HJ, Holtke C, et al. 5-pyrrolidinylsulfonyl isatins as a potential tool for the molecular imaging of caspases in apoptosis. J Med Chem. 2006;49:6704–15.
Kemnitzer W, Drewe J, Jiang S, Zhang H, Wang Y, Zhao J, et al. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 1. Structure-activity relationships of the 4-aryl group. J Med Chem. 2004;47:6299–310.
Kemnitzer W, Drewe J, Jiang S, Zhang H, Zhao J, Crogan-Grundy C, et al. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7, 8-positions. J Med Chem. 2007;50:2858–64.
Kemnitzer W, Drewe J, Jiang S, Zhang H, Crogan-Grundy C, Labreque D, et al. Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. 4. Structure-activity relationships of N-alkyl substituted pyrrole fused at the 7,8-positions. J Med Chem. 2008;51:417–23.
Nguyen QD, Smith G, Glaser M, Perumal M, Arstad E, Aboagye EO. Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-3/7 specific [18F]-labeled isatin sulfonamide. Proc Natl Acad Sci USA. 2009;106:16375–80.
Chen DL, Zhou D, Chu W, Herrbrich PE, Jones LA, Rothfuss JM, et al. Comparison of radiolabeled isatin analogs for imaging apoptosis with positron emission tomography. Nucl Med Biol. 2009;36:651–8.
Podichetty AK, Wagner S, Schroer S, Faust A, Schafers M, Schober O, et al. Fluorinated isatin derivatives. Part 2. New n-substituted 5-pyrrolidinylsulfonyl isatins as potential tools for molecular imaging of caspases in apoptosis. J Med Chem. 2009;52:3484–95.
Crumeyrolle-Arias M, Buneeva O, Zgoda V, Kopylov A, Cardona A, Tournaire MC, et al. Isatin binding proteins in rat brain: in situ imaging, quantitative characterization of specific [3H]isatin binding, and proteomic profiling. J Neurosci Res. 2009;87:2763–72.
Zhou D, Chu W, Chen DL, Wang Q, Reichert DE, Rothfuss J, et al. [18F]- and [11C]-labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging study of apoptosis in Fas-treated mice using [11C]WC-98. Org Biomol Chem. 2009;7:1337–48.
Faust A, Wagner S, Law MP, Hermann S, Schnockel U, Keul P, et al. The nonpeptidyl caspase binding radioligand (S)-1-(4-(2-[18F]Fluoroethoxy)-benzyl)-5-[1-(2-methoxymethylpyrrolidinyl)s ulfonyl]isatin ([18F]CbR) as potential positron emission tomography-compatible apoptosis imaging agent. Q J Nucl Med Mol Imaging. 2007;51:67–73.
Gao M, Wang M, Miller KD, Hutchins GD, Zheng QH. Synthesis of carbon-11-labeled 4-aryl-4H-chromens as new PET agents for imaging of apoptosis in cancer. Appl Radiat Isot. 2010;68:110–6.
Laskin JJ, Sandler AB. Epidermal growth factor receptor: a promising target in solid tumours. Cancer Treat Rev. 2004;30:1–17.
Mishani E, Abourbeh G, Eiblmaier M, Anderson CJ. Imaging of EGFR and EGFR tyrosine kinase overexpression in tumors by nuclear medicine modalities. Curr Pharm Des. 2008;14:2983–98.
Babaei MH, Almqvist Y, Orlova A, Shafii M, Kairemo K, Tolmachev V. [99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo: preparation and pre-clinical evaluation. Oncol Rep. 2005;13:1169–75.
Frederick L, Wang XY, Eley G, James CD. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer Res. 2000;60:1383–7.
Wen X, Wu QP, Ke S, Ellis L, Charnsangavej C, Delpassand AS, et al. Conjugation with 111In-DTPA-poly(ethylene glycol) improves imaging of anti-EGF receptor antibody C225. J Nucl Med. 2001;42:1530–7.
Cai W, Chen K, He L, Cao Q, Koong A, Chen X. Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. Eur J Nucl Med Mol Imaging. 2007;34:850–8.
Liu N, Li M, Li X, Meng X, Yang G, Zhao S, et al. PET-based biodistribution and radiation dosimetry of epidermal growth factor receptor-selective tracer 11C-PD153035 in humans. J Nucl Med. 2009;50:303–8.
Miao Z, Ren G, Liu H, Jiang L, Cheng Z. Small-animal PET imaging of human epidermal growth factor receptor positive tumor with a 64cu labeled affibody protein. Bioconjug Chem. 2010;21:947–54.
Tran TA, Rosik D, Abrahmsen L, Sandstrom M, Sjoberg A, Wallberg H, et al. Design, synthesis and biological evaluation of a multifunctional HER2-specific Affibody molecule for molecular imaging. Eur J Nucl Med Mol Imaging. 2009;36:1864–73.
Tolmachev V, Friedman M, Sandstrom M, Eriksson TL, Rosik D, Hodik M, et al. Affibody molecules for epidermal growth factor receptor targeting in vivo: aspects of dimerization and labeling chemistry. J Nucl Med. 2009;50:274–83.
Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging. 2003;30:781–93.
Forrer F, Valkema R, Kwekkeboom DJ, De Jong M, Krenning EP. Neuroendocrine tumors. Peptide receptor radionuclide therapy. Best Pract Res Clin Endocrinol Metab. 2007;21:111–29.
Wester HJ, Schottelius M, Poethko T, Bruus-Jensen K, Schwaiger M. Radiolabeled carbohydrated somatostatin analogs: a review of the current status. Cancer Biother Radiopharm. 2004;19:231–44.
Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med. 2007;48:508–18.
Wieder H, Beer AJ, Poethko T, Meisetschlaeger G, Wester HJ, Rummeny E, et al. PET/CT with Gluc-Lys-([18F]FP)-TOCA: correlation between uptake, size and arterial perfusion in somatostatin receptor positive lesions. Eur J Nucl Med Mol Imaging. 2008;35:264–71.
Laverman P, McBride WJ, Sharkey RM, Eek A, Joosten L, Oyen WJ, et al. A novel facile method of labeling octreotide with 18F-fluorine. J Nucl Med. 2010;51:454–61.
Wadas TJ, Eiblmaier M, Zheleznyak A, Sherman CD, Ferdani R, Liang K, et al. Preparation and biological evaluation of 64Cu-CB-TE2A-sst2-ANT, a somatostatin antagonist for PET imaging of somatostatin receptor-positive tumors. J Nucl Med. 2008;49:1819–27.
Wheeler KT, Wang LM, Wallen CA, Childers SR, Cline JM, Keng PC, et al. Sigma-2 receptors as a biomarker of proliferation in solid tumours. Br J Cancer. 2000;82:1223–32.
Hashimoto K, Ishiwata K. Sigma receptor ligands: possible application as therapeutic drugs and as radiopharmaceuticals. Curr Pharm Des. 2006;12:3857–76.
Al-Nabulsi I, Mach RH, Wang LM, Wallen CA, Keng PC, Sten K, et al. Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells. Br J Cancer. 1999;81:925–33.
Tu Z, Xu J, Jones LA, Li S, Dumstorff C, Vangveravong S, et al. Fluorine-18-labeled benzamide analogues for imaging the sigma2 receptor status of solid tumors with positron emission tomography. J Med Chem. 2007;50:3194–204.
Tu Z, Xu J, Jones LA, Li S, Zeng D, Kung MP, et al. Radiosynthesis and biological evaluation of a promising sigma(2)-receptor ligand radiolabeled with fluorine-18 or iodine-125 as a PET/SPECT probe for imaging breast cancer. Appl Radiat Isot. 2010;68:2268–73.
Megalizzi V, Le Mercier M, Decaestecker C. Sigma receptors and their ligands in cancer biology: overview and new perspectives for cancer therapy. Med Res Rev. 2010. doi:10.1002/med.20218.
Balkwill F. The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol. 2004;14:171–9.
Busillo JM, Benovic JL. Regulation of CXCR4 signaling. Biochim Biophys Acta. 2007;1768:952–63.
Shim H, Oishi S, Fujii N. Chemokine receptor CXCR4 as a therapeutic target for neuroectodermal tumors. Semin Cancer Biol. 2009;19:123–34.
Kang H, Watkins G, Douglas-Jones A, Mansel RE, Jiang WG. The elevated level of CXCR4 is correlated with nodal metastasis of human breast cancer. Breast. 2005;14:360–7.
Yoon Y, Liang Z, Zhang X, Choe M, Zhu A, Cho HT, et al. CXC chemokine receptor-4 antagonist blocks both growth of primary tumor and metastasis of head and neck cancer in xenograft mouse models. Cancer Res. 2007;67:7518–24.
Jacobson O, Weiss ID, Kiesewetter DO, Farber JM, Chen X. PET of tumor CXCR4 expression with 4-18F-T140. J Nucl Med. 2010;51:1796–804.
Hanaoka H, Mukai T, Tamamura H, Mori T, Ishino S, Ogawa K, et al. Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors. Nucl Med Biol. 2006;33:489–94.
Misra P, Lebeche D, Ly H, Schwarzkopf M, Diaz G, Hajjar RJ, et al. Quantitation of CXCR4 expression in myocardial infarction using 99mTc-labeled SDF-1alpha. J Nucl Med. 2008;49:963–9.
Jacobson O, Weiss ID, Szajek L, Farber JM, Kiesewetter DO. 64Cu-AMD3100–a novel imaging agent for targeting chemokine receptor CXCR4. Bioorg Med Chem. 2009;17:1486–93.
Nimmagadda S, Pullambhatla M, Stone K, Green G, Bhujwalla ZM, Pomper MG. Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100 positron emission tomography. Cancer Res. 2010;70:3935–44.
Shim H, Zhu A, Yoon Y, Liang Z, Voll R, Goodman MM. Development of novel small molecule F-18 labeled CXCR4 PET tracer for head and neck cancer. RSNA 2010. ID 9012133, Chicago, IL.
Acknowledgements
This study was supported by NIH P50 CA 128301-0002 (Shim, H.). We are grateful to Ms. Jessica Paulishen for careful reading of the manuscript and helpful remarks.
Conflict of Interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, A., Shim, H. Current Molecular Imaging Positron Emitting Radiotracers in Oncology. Nucl Med Mol Imaging 45, 1–14 (2011). https://doi.org/10.1007/s13139-011-0075-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13139-011-0075-y