Journal of Literature Pharmacy Sciences

Radyofarmasötikler ve Teranostikler
Radiopharmaceuticals and Theranostics
Meliha EKİNCİa, Derya İLEM ÖZDEMİRa
aEge Üniversitesi, Eczacılık Fakültesi, Radyofarmasi ABD, İzmir, TÜRKİYE
J Lit Pharm Sci. 2021;10(1):119-32
doi: 10.5336/pharmsci.2020-78220
Article Language: TR
ÖZET
Nükleer tıp, hastalıkların görüntülenmesi ve tedavisi amacıyla radyoaktif ilaçların (radyofarmasötiklerin) hasta vücuduna verildiği bir tıp dalıdır. Bir radyofarmasötik, farmasötik ve radyoaktif kısımlardan oluşan ve in vivo kullanım için tasarlanmış bir ilaç formülasyonudur. Radyofarmasötikler, spesifik fizikokimyasal ve radyasyon özelliklerine bağlı olarak teşhis veya terapötik amaçlar için kullanılabilirler. Görüntüleme amacıyla gama (γ) veya pozitron (β+) yayan radyonüklidler ile hazırlanan radyofarmasötikler kullanılırken, tedavi amacıyla çoğunlukla beta (β-) veya alfa (α) partiküler radyasyon yayan radyonüklidler ile hazırlanan radyofarmasötikler kullanılmaktadır. Son yıllarda aynı hastalığın radyonüklid görüntülenmesinde ve tedavisinde aynı veya benzer bir ligandın kullanılması 'teranostik' kavramı ile karşımıza çıkmaktadır. Nükleer tıpta teranostik yaklaşım hem teşhis hem de tedavi amacıyla spesifik moleküler hedefleme için oluşturulmuş bir araçtır. Radyofarmasötiklerin ve teşhis tekniklerinin hızlı gelişimi sayesinde teranostik ajanların geliştirilmesi ve kullanımı sürekli artmaktadır. Bu derlemede; nükleer tıbbın gelişimi, tanı ve tedavi amacıyla kullanılan radyofarmasötikler, nükleer tıptaki güncel gelişmeler ile teranostikler anlatılmış ve güncel çalışmalardan örnekler sunulmuştur.

Anahtar Kelimeler: Nükleer tıp; tanı; tedavi; radyofarmasötik; teranostik
ABSTRACT
Nuclear Medicine is a medical branch in which radioactive drugs (radiopharmaceuticals) are administered to the patient's body for the purpose of imaging and treating diseases. A radiopharmaceutical is a drug formulation consisting of pharmaceutical and radioactive parts and designed for in vivo use. Radiopharmaceuticals can be used for diagnostic or therapeutic purposes depending on their specific physicochemical and radiation properties. While radiopharmaceuticals prepared with radionuclides emitting gamma (γ) or positron (β+) are used for imaging, radiopharmaceuticals prepared with beta (β-) or alpha (α) particle radiation emitting radionuclides are mostly used for treatment. In recent years, the use of the same or similar ligand appears in the concept of 'theranostic' in the radionuclide imaging and treatment of the same disease. In nuclear medicine, the teranostic approach is a tool created for specific molecular targeting for both diagnostic and therapeutic purposes. Thanks to the rapid development of radiopharmaceuticals and diagnostic techniques, the development and use of teranostic agents is constantly increasing. In this review, the development of nuclear medicine, radiopharmaceuticals used for diagnosis and treatment, current developments in nuclear medicine and teranostics are explained and examples from current studies are presented.

Keywords: Nuclear medicine; diagnosis; treatment; radiopharmaceuticals; theranostics
REFERENCES:
  1. Mould RF. A Century of X-rays and Radioactivity in Medicine. 1st ed. London, UK: CRC Press; 1993.
  2. Thomas AM. The first 50 years of military radiology 1895-1945. Eur J Radiol. 2007;63(2):214-9. [Crossref] [PubMed] 
  3. Cassen B, Curtis L, Reed C, Libby R. Instrumentation for 131I use in medical studies. Nucleonics. 1951;9(2):46-50. [Link] 
  4. Wrenn Fr Jr, Good Ml, Handler P. The use of positron-emitting radioisotopes for the localization of brain tumors. Science. 1951;113(2940):525-7. [Crossref] [PubMed] 
  5. Anger HO. Scintillation camera. Review of Scientific Instruments. 1958;29(1):27-33. [Crossref] 
  6. Harper PV, Beck RN, Charleston DB, Lathrop KA. Optimization of a scanning method using Technetium-99m. Nucleonics. 1964;22(1):50-4. [Link] 
  7. Papagiannopoulou D. Technetium-99m radiochemistry for pharmaceutical applications. J Labelled Comp Radiopharm. 2017;60(11):502-20. [Crossref] [PubMed] 
  8. Phelps ME, Hoffman EJ, Mullani NA, Ter-Pogossian MM. Application of annihilation coincidence detection to transaxial reconstruction tomography. J Nucl Med. 1975;16(3):210-24. [PubMed] 
  9. Kuhl DE, Edwards RQ, Ricci AR, Yacob RJ, Mich TJ, Alavi A. The Mark IV system for radionuclide computed tomography of the brain. Radiology. 1976;121(2):405-13. [Crossref]  [PubMed] 
  10. Blankespoor SC, Xu X, Kalki K, Brown JK, Tang HR, Cann CE, et al. Attenuation correction of SPECT using X-ray CT on an emission-transmission CT system: Myocardial perfusion assessment. IEEE Nucl Sci Symp Med Imaging Conf. 1995;43(4):2263-74. [Link] 
  11. Carlsson S. A glance at the history of nuclear medicine. Acta Oncol. 1995;34(8):1095-102. [Crossref] [PubMed] 
  12. Akul M, Nishant G. Radiopharmaceuticals. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020. Erişim linki: [Link]  Erişim tarihi: 20 Haziran 2020.
  13. Cherry SR, Sorenson JA, Phelps ME. Physics in Nuclear Medicine. 4th ed. California: Elsevier Inc; 2012. [Crossref] 
  14. Angelidis G, Giamouzis G, Karagiannis G, Butler J, Tsougos I, Valotassiou V, et al. SPECT and PET in ischemic heart failure. Heart Fail Rev. 2017;22(2):243-61. [Crossref] [PubMed] 
  15. Okudan B, Özbek FM. Günümüzden geleceğe nükleer kardiyoloji. [Nuclear cardýology ýn future and today]. S.D.Ü Tıp Fakültesi Derg. 2009;12(3):57-61. [Link] 
  16. Kiani Nasab M, Rafat Motavalli L, Miri Hakimabad H. Internal dosimetry of inhaled iodine-131. J Environ Radioact. 2018;181:62-9. [Crossref] [PubMed] 
  17. Salmanoglu E, Kim S, Thakur ML. Currently available radiopharmaceuticals for imaging infection and the holy grail. Semin Nucl Med. 2018;48(2):86-99. [Crossref] [PubMed] [PMC] 
  18. Payolla FB, Massabni AC, Orvig C. Radiopharmaceuticals for diagnosis in nuclear medicine: A short review. Eclet Quim. 2019;44(3):11-9. [Crossref] 
  19. Boellaard R, O'Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181-200. [Crossref] [PubMed] [PMC] 
  20. Reves JG. Toward Understanding cerebral blood flow during cardiopulmonary bypass: implications for the central nervous system. Anesthesiology. 2019;130(4):609-13. [Crossref] [PubMed] 
  21. Hong AS, Levin D, Parker L, Rao VM, Ross-Degnan D, Wharam JF. Trends in diagnostic imaging utilization among medicare and commercially insured adults from 2003 through 2016. Radiology. 2020;294(2):342-50. [Crossref] [PubMed] [PMC] 
  22. Knapp FFR, Dash A. Radiopharmaceuticals for therapy. J Nucl Med. 2017;58(9):1526. [Link] 
  23. Zhou SF, Zhong WZ. Drug design and discovery: principles and applications. Molecules. 2017;22(2):279. [Crossref]  [PubMed]  [PMC] 
  24. Baig MH, Ahmad K, Roy S, Ashraf JM, Adil M, Siddiqui MH, Khan et al. Computer aided drug design: success and limitations. Curr Pharm Des. 2016;22(5):572-81. [Crossref] [PubMed] 
  25. Bozkurt MF. Nuclear theranostics in Turkey. Nucl Med Mol Imaging. 2019;53(1):11-13. [Crossref] [PubMed] [PMC] 
  26. Bartholomä MD. Radioimmunotherapy of solid tumors: Approaches on the verge of clinical application. J Labelled Comp Radiopharm. 2018;61(9):715-26. [Crossref] [PubMed] 
  27. Yalım HA, Balçın N, Sarpün İH. Nükleer tıpta kullanılan bakır radyoizotoplarının uyarma fonksiyonlarının talys kodu ile incelenmesi [Investigation of excitation functions of copper radioisotopes used in nuclear medicine with TALYS code]. Süleyman Demirel University Faculty of Arts and Sciences Journal of Science. 2017;12(2):12-8. [Link] 
  28. Baidoo KE, Yong K, Brechbiel MW. Molecular pathways: targeted α-particle radiation therapy. Clin Cancer Res. 2013;19(3):530-7. [Crossref] [PubMed] [PMC] 
  29. Gupta N, Devgan A, Bansal I, Olsavsky TD, Li S, Abdelbaki A, Kumar Y. Usefulness of radium-223 in patients with bone metastases. Proc (Bayl Univ Med Cent). 2017;30(4):424-6. [Crossref] [PubMed] [PMC] 
  30. Keresztes A, Borics A, Tömböly C. Therapeutic and diagnostic radiopharmaceuticals. Sel Top from Contemp Exp Biol. 2015;2:225-47. [Link] 
  31. Niccoli Asabella A, Cascini GL, Altini C, Paparella D, Notaristefano A, Rubini G. The copper radioisotopes: a systematic review with special interest to 64Cu. Biomed Res Int. 2014;2014:786463. Retraction in: Biomed Res Int. 2018;2018:3860745. [Crossref] [PubMed] [PMC] 
  32. Dar MA, Masoodi H, Farooq S. Medical uses of radiopharmaceuticals. PharmaTutor. 2015;3(8):24-9. [Link] 
  33. Kam BL, Teunissen JJ, Krenning EP, de Herder WW, Khan S, van Vliet EI, et al. Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39 Suppl 1(Suppl 1):S103-12. [Crossref] [PubMed] [PMC] 
  34. de Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu-and 90Y-labeled somatostatin analogs. J Nucl Med. 2005;46 Suppl 1:13S-7S. [PubMed] 
  35. Ogawa K, Mukai T, Asano D, Kawashima H, Kinuya S, Shiba K, et al. Therapeutic effects of a 186Re-complex-conjugated bisphosphonate for the palliation of metastatic bone pain in an animal model. J Nucl Med. 2007;48(1):122-7. [PubMed] 
  36. Rebischung C, Hoffmann D, Stefani L, Desruet MD, Wang K, Adelstein SJ, et al. First human treatment of resistant neoplastic meningitis by intrathecal administration of MTX plus (125)IUdR. Int J Radiat Biol. 2008;84(12):1123-9. [Crossref] [PubMed] 
  37. Dave F. Recent advances in cardiac nuclear imaging technology. Diagnostic and interventional cardiology. 19.09.2017 [Link] 
  38. Varasteh Z, Mohanta S, Robu S, Braeuer M, Li Y, Omidvari N, et al. Molecular Imaging of Fibroblast Activity After Myocardial Infarction Using a68Ga-Labeled Fibroblast Activation Protein Inhibitor, FAPI-04. J Nucl Med. 2019;60(12):1743-9. [Crossref] [PubMed] [PMC] 
  39. Sun X, Xiao Z, Chen G, Han Z, Liu Y, Zhang C, et al. A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management. Sci Transl Med. 2018;10(431):eaan8840. [Crossref] [PubMed] 
  40. James ML, Hoehne A, Mayer AT, Lechtenberg K, Moreno M, Gowrishankar G, et al. Imaging B cells in a mouse model of multiple sclerosis using 64Cu-Rituximab PET. J Nucl Med. 2017;58(11):1845-51. [Crossref] [PubMed] [PMC] 
  41. Kuten J, Fahoum I, Savin Z, Shamni O, Gitstein G, Hershkovitz D, et al. Head-to-head comparison of 68Ga-PSMA-11 with 18F-PSMA-1007 PET/CT in staging prostate cancer using histopathology and immunohistochemical analysis as a reference standard. J Nucl Med. 2020;61(4):527-32. [Crossref] [PubMed] 
  42. Andersen TL, Baun C, Olsen BB, Dam JH, Thisgaard H. Improving contrast and detectability: imaging with [55Co]Co-DOTATATE in comparison with [64Cu]Cu-DOTATATE and [68Ga]Ga-DOTATATE. J Nucl Med. 2020;61(2):228-33. [Crossref]  [PubMed] 
  43. Speck I, Arndt S, Thurow J, Blazhenets G, Aschendorff A, Meyer PT, et al. 18F-FDG PET imaging of the inferior colliculus in asymmetric hearing loss. J Nucl Med. 2020;61(3):418-22. [Crossref] [PubMed] 
  44. Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: current advances and future directions. Int J Med Sci. 2012;9(3):193-9. [PubMed] [PMC] 
  45. Kalash RS, Lakshmanan VK, Cho C-S, Park I-K. Theranostics. In: Ebara M, editor. Biomaterials Nanoarchitectonics. 1st ed. Cambridge: Elsevier Inc; 2016. p. 197-215. [Crossref] 
  46. Kelkar SS, Reineke TM. Theranostics: combining imaging and therapy. Bioconjug Chem. 2011 Oct 19;22(10):1879-903. [Crossref]  [PubMed] 
  47. Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliv Rev. 2010;62(11):1052-63. [Crossref] [PubMed] [PMC] 
  48. Langbein T, Weber WA, Eiber M. Future of theranostics: an outlook on precision oncology in nuclear medicine. J Nucl Med. 2019;60(Suppl 2):13S-19S. [Crossref] [PubMed] 
  49. Ma X, Zhao Y, Liang XJ. Theranostic nanoparticles engineered for clinic and pharmaceutics. Acc Chem Res. 2011;44(10):1114-22. [Crossref] [PubMed] 
  50. Vogenberg FR, Isaacson Barash C, Pursel M. Personalized medicine: part 1: evolution and development into theranostics. P T. 2010;35(10):560-76. [PubMed] [PMC] 
  51. Yordanova A, Eppard E, Kürpig S, Bundschuh RA, Schönberger S, Gonzalez-Carmona M, et al. Theranostics in nuclear medicine practice. Onco Targets Ther. 2017;10:4821-8. [Crossref] [PubMed] [PMC] 
  52. Gerard SK, Cavalieri RR. I-123 diagnostic thyroid tumor whole-body scanning with imaging at 6, 24, and 48 hours. Clin Nucl Med. 2002;27(1):1-8. [Crossref] [PubMed] 
  53. Alzahrani AS, AlShaikh O, Tuli M, Al-Sugair A, Alamawi R, Al-Rasheed MM. Diagnostic value of recombinant human thyrotropin-stimulated ¹²³I whole-body scintigraphy in the follow-up of patients with differentiated thyroid cancer. Clin Nucl Med. 2012;37(3):229-34. [Crossref] [PubMed] 
  54. Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: Safety and efficacy. Journal of Nuclear Medicine. 2016;57(7):1006-13. [Crossref]  [PubMed] 
  55. Ahmadzadehfar H, Biersack HJ, Ezziddin S. Radioembolization of liver tumors with yttrium-90 microspheres. Semin Nucl Med. 2010;40(2):105-21. [Crossref] [PubMed] 
  56. Silberstein EB. Radioiodine: the classic theranostic agent. Semin Nucl Med. 2012;42(3):164-70. [Crossref] [PubMed] 
  57. Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014;15(12):1397-406. [Crossref] [PubMed] 
  58. Al-Mayouf SM, Almutairi N, Alismail K. The efficacy of yttrium-90 radiosynovectomy in patients with camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Mol Imaging Radionucl Ther. 2017;26(1):33-7. [Crossref] [PubMed] [PMC] 
  59. Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR. 123I-meta-iodobenzylguanidine scintigraphy for the detection of neuroblastoma and pheochromocytoma: results of a meta-analysis. J Clin Endocrinol Metab. 2010;95(6):2596-606. [Crossref] [PubMed] 
  60. Romer A, Seiler D, Marincek N, Brunner P, Koller MT, Ng QK, et al. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2014;41(2):214-22. [Crossref] [PubMed] 
  61. Palmedo H, Manka-Waluch A, Albers P, Schmidt-Wolf IG, Reinhardt M, Ezziddin S, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol. 2003;21(15):2869-75. [Crossref] [PubMed] 
  62. Aerts A, Impens NR, Gijs M, D'Huyvetter M, Vanmarcke H, Ponsard B, et al. Biological carrier molecules of radiopharmaceuticals for molecular cancer imaging and targeted cancer therapy. Curr Pharm Des. 2014;20(32):5218-44. [Crossref] [PubMed] 
  63. Witzig TE. Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin's lymphoma. Drugs Today (Barc). 2004;40(2):111-9. [Crossref] [PubMed] 
  64. Mier W, Kratochwil C, Hassel JC, Giesel FL, Beijer B, Babich JW, et al. Radiopharmaceutical therapy of patients with metastasized melanoma with the melanin-binding benzamide 131I-BA52. J Nucl Med. 2014;55(1):9-14. [Crossref] [PubMed] 
  65. Ferreira CA, Ehlerding EB, Rosenkrans ZT, Jiang D, Sun T, Aluicio-Sarduy E, et al. 86/90Y-labeled monoclonal antibody targeting tissue factor for pancreatic cancer theranostics. Mol Pharm. 2020;17(5):1697-705. [Crossref]  [PubMed]  [PMC] 
  66. Jing H, Weidensteiner C, Reichardt W, Gaedicke S, Zhu X, Grosu AL, et al. Imaging and selective elimination of glioblastoma stem cells with theranostic near-infrared-labeled CD133-Specific antibodies. Theranostics. 2016;6(6):862-74. [Crossref] [PubMed] [PMC] 
  67. Lim EK, Huh YM, Yang J, Lee K, Suh JS, Haam S. pH-triggered drug-releasing magnetic nanoparticles for cancer therapy guided by molecular imaging by MRI. Adv Mater. 2011;23(21):2436-42. [Crossref] [PubMed] 
  68. Wang LS, Chuang MC, Ho JA. Nanotheranostics--a review of recent publications. Int J Nanomedicine. 2012;7:4679-95. [Crossref] [PubMed] [PMC] 
  69. Moghimi SM, Hunter AC, Murray JC. Nanomedicine: current status and future prospects. FASEB J. 2005;19(3):311-30. [Crossref] [PubMed] 
  70. Kim D, Jeong YY, Jon S. A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. ACS Nano. 2010;4(7):3689-96. [PubMed] 
  71. Moon GD, Choi SW, Cai X, Li W, Cho EC, Jeong U, et al. A new theranostic system based on gold nanocages and phase-change materials with unique features for photoacoustic imaging and controlled release. J Am Chem Soc. 2011;133(13):4762-5. [Crossref] [PubMed] [PMC] 
  72. Heo DN, Yang DH, Moon HJ, Lee JB, Bae MS, Lee SC, et al. Gold nanoparticles surface-functionalized with paclitaxel drug and biotin receptor as theranostic agents for cancer therapy. Biomaterials. 2012;33(3):856-66. [Crossref]  [PubMed] 
  73. Huang P, Bao L, Zhang C, Lin J, Luo T, Yang D, et al. Folic acid-conjugated silica-modified gold nanorods for X-ray/CT imaging-guided dual-mode radiation and photo-thermal therapy. Biomaterials. 2011;32(36):9796-809. [Crossref] [PubMed] 
  74. Park JK, Jung J, Subramaniam P, Shah BP, Kim C, Lee JK, et al. Graphite-coated magnetic nanoparticles as multimodal imaging probes and cooperative therapeutic agents for tumor cells. Small. 2011;7(12):1647-52. [Crossref] [PubMed] [PMC] 
  75. Karpuz M, Silindir-Gunay M, Kursunel MA, Esendagli G, Dogan A, Ozer AY. Design and in vitro evaluation of folate-targeted, co-drug encapsulated theranostic liposomes for non-small cell lung cancer. J Drug Deliv Sci Technol. 2020;57:101707. [Crossref] 

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4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com