Dataset Open Access
Moldovan, Rares-Petru; Gündel, Daniel; Deuther-Conrad, Winnie; Ueberham, Lea; Kaur, Sarandeep; Otikova, Elina; Teodoro, Rodrigo; Lai, Thu Hang; Clauß, Oliver; Scheunemann, Matthias; Bormans, Guy; Kopka, Klaus; Bachmann, Michael; Brust, Peter
<?xml version='1.0' encoding='UTF-8'?> <record xmlns="http://www.loc.gov/MARC21/slim"> <leader>00000nmm##2200000uu#4500</leader> <controlfield tag="005">20220810123836.0</controlfield> <controlfield tag="001">1381</controlfield> <datafield tag="773" ind1=" " ind2=" "> <subfield code="a">https://www.hzdr.de/publications/Publ-34030</subfield> <subfield code="i">isIdenticalTo</subfield> <subfield code="n">url</subfield> </datafield> <datafield tag="773" ind1=" " ind2=" "> <subfield code="a">https://www.hzdr.de/publications/Publ-33987</subfield> <subfield code="i">isReferencedBy</subfield> <subfield code="n">url</subfield> </datafield> <datafield tag="773" ind1=" " ind2=" "> <subfield code="a">10.14278/rodare.1380</subfield> <subfield code="i">isVersionOf</subfield> <subfield code="n">doi</subfield> </datafield> <datafield tag="540" ind1=" " ind2=" "> <subfield code="u">https://creativecommons.org/licenses/by/4.0/legalcode</subfield> <subfield code="a">Creative Commons Attribution 4.0 International</subfield> </datafield> <datafield tag="260" ind1=" " ind2=" "> <subfield code="c">2022-08-09</subfield> </datafield> <datafield tag="100" ind1=" " ind2=" "> <subfield code="a">Moldovan, Rares-Petru</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0003-3119-7945</subfield> </datafield> <datafield tag="245" ind1=" " ind2=" "> <subfield code="a">Data Publication: Structure-Based Design, Optimization and Development of [18F]LU13, a novel radioligand for CB2R Imaging in the Brain with PET</subfield> </datafield> <datafield tag="909" ind1="C" ind2="O"> <subfield code="o">oai:rodare.hzdr.de:1381</subfield> <subfield code="p">openaire_data</subfield> <subfield code="p">user-health</subfield> <subfield code="p">user-rodare</subfield> </datafield> <datafield tag="650" ind1="1" ind2="7"> <subfield code="a">cc-by</subfield> <subfield code="2">opendefinition.org</subfield> </datafield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="a">dataset</subfield> </datafield> <datafield tag="520" ind1=" " ind2=" "> <subfield code="a"><p>The cannabinoid receptor type 2 (CB2R) is an attractive target for diagnosis and therapy of neurodegenerative diseases and cancer. Recently, we reported a novel naphthyrid-2-one based positron-emission tomography (PET) radioligand for imaging of the CB2R in the brain (<strong>[<sup>18</sup>F]5</strong>). In this study we aimed at the development of a novel <sup>18</sup>F-labeled CB2R radioligand with improved binding properties and metabolic stability. Starting from the structure of <strong>5</strong>, we developed a novel series of fluorinated derivatives by modifying the substituents at the naphthyrid-2-one subunit. Compound <strong>28</strong> (<strong>LU13</strong>) was identified with the highest binding affinity and selectivity versus CB1R (CB2R<em>K</em><sub>i</sub> = 0.6 nM; CB1R<em>K</em><sub>i</sub>/CB2R<em>K</em><sub>i</sub> &gt; 1000) and was selected for radiolabeling with <sup>18</sup>F and biological characterization. The radiofluorination was performed starting from the corresponding bromo-precursor (<strong>31</strong>) bearing a fully deuterated <em>N</em>-alkyl chain to protect against defluorination. The in vitro evaluation of <strong>[<sup>18</sup>F]LU13 </strong>proved the high binding affinity of the radioligand towards rat (rCB2R<em>K</em><sub>D</sub> = 0.2 nM) and human (hCB2R<em>K</em><sub>D</sub> = 1.1 nM) CB2R. Metabolism studies in mice revealed a metabolic stability at 30 min p.i. with fractions of parent compound of &gt;80% in the brain and 90% in the spleen with only trace of defluorination products detected in plasma. PET imaging in a rat model of vector-based/related overexpression in the striatum revealed a high signal to background ratio, demonstrating the ability of <strong>[<sup>18</sup>F]LU13</strong> to reach and selectively label the hCB2R in the brain. Thus, <strong>[<sup>18</sup>F]LU13 </strong>is a novel and highly promising PET radioligand for the imaging of up regulated CB2R expression under pathological conditions in the brain.</p></subfield> </datafield> <datafield tag="542" ind1=" " ind2=" "> <subfield code="l">open</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">cannabinoid receptor type 2</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">naphthyrid-2-one</subfield> </datafield> <datafield tag="653" ind1=" " ind2=" "> <subfield code="a">binding affinity</subfield> </datafield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="a">user-health</subfield> </datafield> <datafield tag="980" ind1=" " ind2=" "> <subfield code="a">user-rodare</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Gündel, Daniel</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0001-9743-2325</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Deuther-Conrad, Winnie</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0003-3168-3062</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Ueberham, Lea</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Kaur, Sarandeep</subfield> <subfield code="u">HZDR</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Otikova, Elina</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Teodoro, Rodrigo</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0002-1425-0567</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Lai, Thu Hang</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0001-8157-8979</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Clauß, Oliver</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0001-5067-4845</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Scheunemann, Matthias</subfield> <subfield code="u">HZDR</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Bormans, Guy</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Kopka, Klaus</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0003-4846-1271</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Bachmann, Michael</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0002-8029-5755</subfield> </datafield> <datafield tag="700" ind1=" " ind2=" "> <subfield code="a">Brust, Peter</subfield> <subfield code="u">HZDR</subfield> <subfield code="0">(orcid)0000-0001-5555-7058</subfield> </datafield> <datafield tag="856" ind1="4" ind2=" "> <subfield code="s">159811</subfield> <subfield code="u">https://rodare.hzdr.de/record/1381/files/PPT_LU13_HPLC.7z</subfield> <subfield code="z">md5:b5d90aab3caacfc3d8e5e32361b9fa5d</subfield> </datafield> <datafield tag="024" ind1=" " ind2=" "> <subfield code="a">10.14278/rodare.1381</subfield> <subfield code="2">doi</subfield> </datafield> </record>
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