Abstract
Because of the importance of epidermal growth factor receptor (EGFR) signaling pathway in oncogenesis, maintenance, and progression of different types of tumors, there has been an intense effort to develop non-invasive imaging approaches for selection and monitoring of EGFR-targeted therapies. During the past decade, EGFR-tyrosine kinase inhibitors have been explored as potential radiotracers for positron emission tomography (PET) imaging of EGFR over-expressing tumors. The development of agents for PET imaging of EGFR at the tyrosine kinase level has been so far based exclusively on anilinoquinazoline core structure, which has been “borrowed” as the key pharmacophore from the leading EGFR-inhibitory pharmaceuticals. The I-124, F-18, and C-11 radiolabeled irreversible inhibitors of EGFR demonstrate the greatest potential for derivatization into effective EGFR kinase imaging agents. PET imaging with radiolabeled agents specific for activated forms of EGFR kinase will facilitate the selection (stratification) of patients which will have more favorable responses to therapy with EGFR signaling inhibitors.
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Baselga, J. (2001). Targeting the epidermal growth factor receptor: a clinical reality. Journal of Clinical Oncology, 19(Suppl. 18), 41S–44S.
Arteaga, C. L. (2001). The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. Journal of Clinical Oncology, 19, 32S–40S.
Mendelsohn, J. (2002). Targeting the epidermal growth factor receptor for cancer therapy. Journal of Clinical Oncology, 20, 1S–13S.
Grünwald, V., & Hidalgo, M. (2003). Developing inhibitors of the epidermal growth factor receptor for cancer therapy. Journal of the National Cancer Institute, 95, 851–867.
Mendelson, J., & Baselga, J. (2003). Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. Journal of Clinical Oncology, 21, 2787–2799.
Lynch, T. J., Bell, D. W., Sordella, R., et al. (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. New England Journal of Medicine, 20, 2129–2139.
Sordella, R., Bell, D. W., Haber, D. A., et al. (2004). Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science, 20, 1163–1167.
Pao, W., Miller, V., Zakowski, M., et al. (2004). EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proceedings of the National Academy of Sciences of the United States of America, 101, 13306–13311.
Huang, S. F., Liu, H. P., Li, L., et al. (2005). High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan. Clinical Cancer Research, 10, 8195–8203.
Rich, J. N., Reardon, D. A., Peery, T., et al. (2004). Phase II trial of gefitinib in recurrent glioblastoma. Journal of Clinical Oncology, 22, 133–142.
Learn, C. A., Hartzell, T. L., Wikstrand, C. J., et al. (2004). Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme. Clinical Cancer Research, 10, 3216–3124.
Wang, J.-Q., Gao, M., Miller, K. D., Sledge, G. W., & Zheng, Q.-H. (2006). Synthesis of [11C]Iressa as a new potential PET cancer imaging agent for epidermal growth factor receptor tyrosine kinase. Bioorganic & Medicinal Chemistry, 16, 4102–4106.
Pal, A., Glekas, A., Doubrovin, M., Balatoni, J., Beresten, T., Maxwell, D., et al. (2006). Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small molecular tracer and positron emission tomography. Molecular Imaging and Biology, 8, 262–277.
Mishani, E., Abourbeh, G., Jacobson, O., Dissoki, S., Ben-Daniel, R., & Levitzki, A. (2005). High affinity EGFR irreversible inhibitors with diminished chemical reactivities as PET imaging agent candidates of EGFR irreversible over-expressing tumors. Journal of Medicinal Chemistry, 48(16), 5337–5348.
Bonasera, T. A., Ortu, G., Rozen, Y., et al. (2001). Potential (18)F-labeled biomarkers for epidermal growth factor receptor tyrosine kinase. Nuclear Medicine and Biology, 28, 359–374.
Fredriksson, A., Johnstrom, P., Thorell, J. O., et al. (1999). In vivo evaluation of the biodistribution of 11C-labeled PD153035 in rats without and with neuroblastoma implants. Life Sciences, 65, 165–174.
Ortu, G., Ben-David, I., Rozen, Y., et al. (2002). Labeled EGFr-TK irreversible inhibitor (ML03): in vitro and in vivo properties, potential as PET biomarker for cancer and feasibility as anticancer drug. International Journal of Cancer, 101, 360–370.
Mishani, E., Abourbeh, G., Rozen, Y., et al. (2004). Novel carbon-11 labeled 4-dimethylamino-but-2-enoic acid [4-(phenylamino)-quinazoline-6-yl]-amides: potential PET bioprobes for molecular imaging of EGFR-positive tumors. Nuclear Medicine and Biology, 31, 469–476.
Gazdar, A. F., & Minna, J. D. (2005). Inhibition of EGFR signaling: all mutations are not created equal. PLoS Medicine, 2, e377.
Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., et al. (2005). EGFR mutation and resistance of non-small-cell lung cancer to Gefitinib. New England Journal of Medicine, 352, 786–792.
Kwak, E. L., Sordella, R., Bell, D. W., Godin-Heymann, N., Okimoto, R. A., Brannigan, B. W., et al. (2005). Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proceedings of the National Academy of Sciences of the United States of America, 102, 7665–7670.
Tsou, H.-R., Mamuya, N., Johnson, B. D., Reich, M. F., Gruber, B. C., Ye, F., et al. (2001). 6-substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity. Journal of Medicinal Chemistry, 44, 2719–2734.
Yoshimura, N., Kudoh, S., Kimura, T., Mitsuoka, S., Matsuura, K., Hirata, K., et al. (2006). EKB-569, a new irreversible epidermal growth factor receptor tyrosine kinase inhibitor, with clinical activity in patients with nonsmall cell lung cancer with acquired resistance to gefitinib. Lung Cancer, 51, 363–368.
Vasdev, N., Dorff, P. N., Gibbs, A. R., Nandanan, E., Reid, L. M., O’Neil, J. P., et al. (2005). Synthesis of 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline: a prospective irreversible EGFR binding probe. Journal of Labelled Compounds & Radiopharmaceuticals, 48, 109–115.
Dissoki, S., Laky, D., & Mishani, E. (2006). Fluorine-18 labeling of ML04—presently the most promising irreversible inhibitor candidate for visualization of EGFR in cancer. Journal of Labelled Compounds & Radiopharmaceuticals, 49, 533–543.
Abourbeh, G., Dissoki, S., Jacobson, O., Litchi, A., Ben-Daniel, R., Laki, D., et al. (2007). Evaluation of radiolabeled ML04, a putative irreversible inhibitor of the epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR overexpressing tumors. Nuclear Medicine and Biology, 34, 55–70.
Shaul, M., Abourbeh, G., Jacobson, O., et al. (2004). Novel iodine-124 labeled EGFR inhibitors as potential PET agents for molecular imaging in cancer. Bioorganic & Medicinal Chemistry, 12, 3421–3429.
Matar, P., Rojo, F., Cassia, R., et al. (2004). Combined epidermal growth factor receptor targeting with the tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody Cetuximab (IMC-C225): superiority over single-agent receptor targeting. Clinical Cancer Research, 10, 6487–6501.
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Gelovani, J.G. Molecular imaging of epidermal growth factor receptor expression–activity at the kinase level in tumors with positron emission tomography. Cancer Metastasis Rev 27, 645–653 (2008). https://doi.org/10.1007/s10555-008-9156-5
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DOI: https://doi.org/10.1007/s10555-008-9156-5