This title appears in the Scientific Report :
2014
Please use the identifier:
http://hdl.handle.net/2128/8099 in citations.
Produktion von Bromisotopen und ihre Anwendung zur Entwicklung radiobromierter Adenosin-Rezeptorliganden
Produktion von Bromisotopen und ihre Anwendung zur Entwicklung radiobromierter Adenosin-Rezeptorliganden
For a re-evaluation of production routes of the medically interesting radioisotopes $^{75}$Br, ${76}$Br,$^{77}$Br and $^{82}$Br, cross sections of deuteron induced reactions on natural selenium weremeasured in the energy range up to 41 MeV. Here, measurements of nuclear reactions on$^{nat}$Se leadin...
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Personal Name(s): | Breunig, Katharina (Corresponding Author) |
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Contributing Institute: |
Nuklearchemie; INM-5 |
Published in: | 2014 |
Imprint: |
Jülich
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
2014
|
Physical Description: |
161 p |
Dissertation Note: |
Dissertation, Universität zu Köln, 2014 |
Document Type: |
Report Book Dissertation / PhD Thesis |
Research Program: |
Neuroimaging Pathophysiological Mechanisms of Neurological and Psychiatric Diseases |
Series Title: |
Berichte des Forschungszentrums Jülich
4378 |
Subject (ZB): | |
Link: |
OpenAccess |
Publikationsportal JuSER |
For a re-evaluation of production routes of the medically interesting radioisotopes $^{75}$Br, ${76}$Br,$^{77}$Br and $^{82}$Br, cross sections of deuteron induced reactions on natural selenium weremeasured in the energy range up to 41 MeV. Here, measurements of nuclear reactions on$^{nat}$Se leading to the formation of the neutron deficient isotopes were done for the first time.The new data of the $^{nat}$Se(d,xn)$^{75}$Br process indicate that the promising PET nuclide $^{75}$Br can be produced via the $^{74}$Se(d,n)-reaction in isotopically pure form using deuterons from 10 MeVupwards. Assuming an enrichment of 100 % $^{74}$Se, a sufficient production yield of ca.1 GBq/$\mu$Ah $^{75}$Br is to be expected by covering the energy range 15 $\rightarrow$ 2 MeV. In comparison to the commonly used $^{76}$Se(p,2n)-route, the (d,n)-reaction proceeds at markedly lowerprojectile energies and the isotopic contamination of longer-lived $^{76}$Br could be avoided. For removing discrepancies in the literature data of$\alpha$-particle induced reactions on arsenic, reaction cross section measurements concerning the nuclear processes $^{75}$As($\alpha$,xn)$^{76,77,78}$Br and $^{75}$As($\alpha$,x)$^{74}$As were performed in the energy range of 8 to 38 MeV and integral productionyields were calculated. Here, the ratio of monitor nuclides $^{67}$Ga/$^{66}$Ga permitted an improveddetermination of the $\alpha$-particle energies as well as the resulting beam current, and thus of theexperimental data. Aiming at routine production of radiobromine, a new high-current selenium based target wasdesigned and the already known dry distillation procedure for the isolation of n.c.a. [*Br]bromine from the target material was optimized. Compared to the conventionally used Cu$_{2}$Se, the new target material NiSe contains a 1.5 times higher amount of selenium, hence resulting in significantly higher production yields. The optimized dry distillation method enables high, reproducible yields of 76 - 86 %. By using a quartz capillary for trapping the radiobromine, the handling of this method was improved and the possibility for (semi-)automation was given. Moreover the volume of the radioactivity solution was significantlyreduced to less than 100 $\mu$l compared to previous approaches. The obtained n.c.a. [*Br]bromide of high radiochemical purity is immediately available for subsequent radiosyntheses. Using this n.c.a. [*Br]bromide solution the radiosynthesis of the first radiobrominated A$_{1}$-adenosine receptor ligand [*Br]CPBPX (8-cyclopentyl-3-[(E)-3-[*Br]bromoprop-2-en-1-yl]-1-propylxanthine) was optimized with respect to the most important reaction parameters. Since the $^{131}$l-analogue [$^{131}$l]CPIPX as well as the $^{18}$F-labelled [$^{18}$F]CPFPX already exist, [*Br]CPBPX closes the gap of lipophilicity in this cyclopentylxanthine series. Under optimum reaction conditions [*Br]CPBPX was obtained in radiochemical yields of 43 ± 7 % with aspecific activity of 8.6 GBq/$\mu$mol. By $\textit{in vitro}$ competition experiments for CPBPX a K$_{l}$-value of 26 nM was determined that indicates a quite good affinity to the target receptor. In autoradiographic binding studies on rat brain slices the radioligand [*Br]CPBPX showed an increased accumulation in brain areas of high A$_{1}$AR density with a specific binding of ca. 20 %. So, with [*Br]CPBPX a new radioligand is available for sytematic pre-clinical evaluation. |