ABSTRACT
Radyofarmasötikler, vücutta takip edilmesi amaçlanan mekanizmaya uygun biyoaktif bir molekül ile bir radyoizotoptan oluşur. Doğada bulunan radyoizotoplar Nükleer Tıpta kullanılmaya uygun olmadığı için nükleer reaktörler, siklotronlar ve radyonüklid jeneratörler gibi yapay yollarla elde edilmeleri gerekir. Bu bilgiler doğrultusunda bu makalede; medikal siklotronlarda katı hedeflerin protonla ışınlanmasıyla oluşan pozitron yayıcı radyoizotopların (Zr-89, I-124, Ga-68, Cu-64 ve Sc-44), üretimi ve kullanımıyla ilgili özet bilgilerin derlenmesi amaçlanmıştır.
Keywords:
Pozitron yayıcı, siklotron, radyoizotop, katı hedef, radyofarmasötik
References
1
MEDraysintell report, Cyclotrons used in Nuclear Medicine, World Market Report & Directory, Edition 2020.
2
Talip Z, Favaretto C, Geistlich S, Meulen NPV. A Step-by-Step Guide for the Novel Radiometal Production for Medical Applications: Case Studies with 68Ga, 44Sc, 177Lu and 161Tb. Molecules 2020;25:966.
3
Synowiecki MA, Perk LR, Nijsen JFW. Production of novel diagnostic radionuclides in small medical cyclotrons. EJNMMI Radiopharm Chem 2018;3:3.
4
Standardized high current solid targets for cyclotron production of diagnostic and therapeutic radionuclides. Technical reports series No. 432, Vienna 2004.
5
International Atomic Energy Agency. Alternative radionuclide production with a cyclotron. Radioisotopes and radiopharmaceuticals reports No. 4.
6
Ikotun OF, Lapi SE. The rise of metal radionuclides in medical imaging: copper-64, zirconium-89 and yttrium-86. Future Med Chem 2011;3:599-621.
7
Pandey MK, Bansal A, Ellinghuysen JR, Vail DJ, Berg HM, DeGrado TR. A new solid target design for the production of 89Zr and radiosynthesis of high molar activity [89Zr]Zr-DBN. Am J Nucl Med Mol Imaging 2022;12:15-24.
8
Alfuraih A, Alzimami K, Andy KM, Alghamdi A, Al Jammaz I. Effective dose to immuno-PET patients due to metastable impurities in cyclotron produced zirconium-89. Radiat Phys Chem 2014;104:145-149.
9
Jalilian AR, and Osso JA. Production, applications and status of zirconium-89 immunoPET agents. J Radioanal Nucl Chem 2017;314:7-21.
10
Novel Chelating Agents for Zirconium-89-Positron Emission Tomography (PET) Imaging: Synthesis, DFT Calculation, Radiolabeling, and In Vitro and In Vivo Complex Stability. ACS Omega 2022;7:37229-37236.
11
Holik HA, Ibrahim FM, Elaine AA, Putra BD, Achmad A, Kartamihardja AHS. The Chemical Scaffold of Theranostic Radiopharmaceuticals: Radionuclide, Bifunctional Chelator, and Pharmacokinetics Modifying Linker. Molecules 2022;27:3062.
12
Braghirolli AM, Waissmann W, da Silva JB, dos Santos GR. Production of iodine-124 and its applications in nuclear medicine. Appl Radiat Isot 2014;90:138-148.
13
Bzowski P, Borys D, Gorczewski K, et al. Efficiency of 124I radioisotope production from natural and enriched tellurium dioxide using 124Te(p,xn)124I reaction. EJNMMI Phys 20226;9:41.
14
Fonslet J, and Koziorowski J. Dry distillation of radioiodine from TeO2 targets. Appl Sci 2013;3:675-683.
15
International Atomic Energy Agency. Gallium-68 cyclotron production. Tecdoc-1863, Vienna 2019.
16
Gallium (68Ga) chloride (accelerator-produced) solution for radiolabeling. European Pharmacopoeia 04/2023/3109.
17
Gallium chloride (68Ga) solution for radiolabelling. European Pharmacopoeia 07/2013/2464.
18
Follacchio GA, De Feo MS, De Vincenti G, et al. Radiopharmaceuticals Labelled with Copper Radionuclides: Clinical Results in Human Beings. Curr Radiopharm 2018;11:22-33.
19
Boschi A, Martini P, Janevik-Ivanovska E, Duatti A. The emerging role of copper-64 radiopharmaceuticals as cancer theranostics. Drug Discov Today 2018;23:1489-1501.
20
Zhou Y, Li J, Xu X, et al. 64Cu-based Radiopharmaceuticals in Molecular Imaging. Technol Cancer Res Treat 2019;18:1533033819830758.
21
George JH, Borjian S, Cross MC, et al. Expanding the PET radioisotope universe utilizing solid targets on small medical cyclotrons. RSC Adv 2021;11:31098-31123.
22
Ahmedova A, Todorov B, Burdzhiev N, Goze C. Copper radiopharmaceuticals for theranostic applications. Eur J Med Chem 2018;157:1406-1425.
23
van der Meulen NP, Hasler R, Talip Z, et al. Developments toward the Implementation of 44Sc Production at a Medical Cyclotron Molecules 2020;25:4706.
24
Pruszyński M, Majkowska-Pilip A, Loktionova NS, Eppard E, Roesch F. Radiolabeling of DOTATOC with the long-lived positron emitter 44Sc. Appl Radiat Isot 2012;70:974-979.
25
Müller C, Domnanich KA, Umbricht CA, van der Meulen NP. Scandium and terbium radionuclides for radiotheranostics: current state of development towards clinical application. Br J Radiol 2018;91:20180074.
26
Eppard E. Pre-Therapeutic Dosimetry Employing Scandium-44 for Radiolabeling PSMA-617. Prostatectomy 2018:1-20.
27
Filosofov DV, Loktionova NS, Rösch F. A 44Ti/44Sc radionuclide generator for potential application of 44Sc-based PET-radiopharmaceuticals. Radiochim Acta 2010;98:149-156.
28
Severin GW, Engle JW, Valdovinos HF, Barnhart TE, Nickles RJ. Cyclotron produced ⁴⁴gSc from natural calcium. Appl Radiat Isot 2012;70:1526-1530.
29
Krajewski S, Cydzik I, Abbas K, et al. Cyclotron production of 44Sc for clinical application. Radiochim Acta 2013;101:333-338.
30
Valdovinos HF, Hernandez R, Barnhart TE, Graves S, Cai W, Nickles RJ. Separation of cyclotron-produced 44Sc from a natural calcium target using a dipentyl pentylphosphonate functionalized extraction resin. Appl Radiat Isot 2015;95:23-29.
31
van der Meulen NP, Bunka M, Domnanich KA, et al. Cyclotron production of (44)Sc: From bench to bedside. Nucl Med Biol 2015;42:745-751.
32
Müller C, Bunka M, Reber J, et al. Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β--emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate. J Nucl Med 2013;54:2168-2174.
33
Singh A, van der Meulen NP, Müller C, et al. First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced 44Sc-DOTATOC: A Proof-of-Concept Study. Cancer Biother Radiopharm 2017;32:124-132.
34
Eppard E, de la Fuente A, Benešová M, et al. Clinical Translation and First In-Human Use of [44Sc]Sc-PSMA-617 for PET Imaging of Metastasized Castrate-Resistant Prostate Cancer. Theranostics 2017;7:4359-4369.
