001026489 001__ 1026489
001026489 005__ 20250203103354.0
001026489 037__ $$aFZJ-2024-03433
001026489 041__ $$aEnglish
001026489 1001_ $$0P:(DE-Juel1)180770$$aHoffmann, Chris$$b0$$eCorresponding author
001026489 1112_ $$a25th International Symposium on Radiopharmaceutical Sciences$$cHonolulu, USA$$d2023-05-22 - 2023-05-26$$gISRS2023$$wUSA
001026489 245__ $$aPreparation and preclinical evaluation of novel 18F-labeled FAP ligands
001026489 260__ $$c2023
001026489 3367_ $$033$$2EndNote$$aConference Paper
001026489 3367_ $$2DataCite$$aOther
001026489 3367_ $$2BibTeX$$aINPROCEEDINGS
001026489 3367_ $$2DRIVER$$aconferenceObject
001026489 3367_ $$2ORCID$$aLECTURE_SPEECH
001026489 3367_ $$0PUB:(DE-HGF)6$$2PUB:(DE-HGF)$$aConference Presentation$$bconf$$mconf$$s1716783555_27576$$xAfter Call
001026489 520__ $$aObjectives: Fibroblast activation protein (FAP) is a membraneboundprolyl endopeptidase that is almost exclusively expressed bycancer-associated fibroblasts (CAFs), making it a promising target forpositron emission tomography (PET) imaging of different solid tumors.The aim of this study was the preparation and preclinical evaluation ofthree novel radiofluorinated candidate probes for FAP imaging usingradiolabeling protocols developed in our institute.Methods: [18F]AlF-FAPI-42 ([18F]1) was prepared by chelation of[18F]F– using FAPI-42 precursor (62 nmol) and AlCl3 (30 nmol) inDMSO/50 mM NaOAc buffer (pH 4) mixture (1.4 mL/0.4 mL) at 110 °Cfor 10 min. 7-[18F]F-1-Me-2-aza-IA-FAPI ([18F]2) was obtained byconjugation of appropriately modified AMC1110 with 7-[18F]F-1-Me-2-aza-IA. The latter was prepared from the respective N,N,N-trimethylammoniumtriflate precursor using (on-cartridge) radiofluorination.6-[18F]F-UAMC1110 ([18F]4) was produced from the respective Me3Snsubstrate (10 μmol) using an optimized protocol for Cu-mediatedradiofluorination, while 6-[18F]FSO2-AMC1110 ([18F]3) was preparedby using of an improved procedure for 18F/19F SuFEx isotopic exchangefrom 3 (45 nmol). All tracers were purified by HPLC or SPE. The tracercandidates were evaluated by in vivo μPET (120 min emission scanswith a Siemens Focus 220 small animal PET scanner) in immunodeficientSCID mice subcutaneously inoculated with wild type and FAP+transfected HT-1080 cells. The most promising candidate wasadditionally evaluated in a subcutaneous rat model based on the ratpancreatic tumor cell line DSL-6A/C1, which is characterized by apronounced tumor stroma with a high density of cancer-associatedfibroblasts (CAFs). [18F]AlF-FAPI-42 was applied as the reference FAPspecificPET-tracer in all biological experiments.Results: PET probes were prepared as injectable solutions inactivity yields of 25–57% and with molar activities of 28–170 GBq/μmol. The in vivo PET measurements demonstrated no accumulation inFAP+-HT-1080 tissue for both [18F]2 and [18F]3, reflecting insufficient ofin vivo stability of [18F]3, and the missing FAP selectivity for [18F]2. Incontrast, [18F]4 demonstrated high accumulation in FAP+ tissue andhigh stability in tumor. Uptake of the latter tracer and [18F]1 in FAP+-HT-1080 tumors were comparable and at least twice as high as in wildtype tumors. [18F]4 also enabled a clean delineation of DSL-6A/C1tumors with a target-to-background ratio of about 5, which remainedstable for at least 120 min. In the same model, [18F]1-PET allowedvisualization of tumors with a target-to-background ratio of 10 at40 min p.i., which increased to 15 at 120 min p.i. The higher tumor-tobackgroundratio of [18F]1 was due to lower background activity ratherthan higher tumor uptake. Both [18F]4 and [18F]1 accumulated in galland urinary bladder. [18F]4 showed a particularly strong hepatobiliaryexcretion, resulting in high amounts of radioactivity in the intestinaltract.Conclusions Three novel PET-probes were successfully producedusing emerging radiofluorination methods. Among them [18F]4represents a promising candidate for visualization of FAP-positivetumors. However, it is not superior to [18F]1 because of its higherbackground activity and stronger hepatobiliary excretion.
001026489 536__ $$0G:(DE-HGF)POF4-5253$$a5253 - Neuroimaging (POF4-525)$$cPOF4-525$$fPOF IV$$x0
001026489 7001_ $$0P:(DE-Juel1)180812$$aGröner, Benedikt$$b1
001026489 7001_ $$0P:(DE-Juel1)180982$$aWalter, Nils$$b2
001026489 7001_ $$0P:(DE-Juel1)180330$$aEndepols, Heike$$b3
001026489 7001_ $$0P:(DE-HGF)0$$aGrüll, Holger$$b4
001026489 7001_ $$0P:(DE-Juel1)175142$$aNeumaier, Felix$$b5
001026489 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b6
001026489 7001_ $$0P:(DE-Juel1)185610$$aZlatopolskiy, Boris$$b7
001026489 8564_ $$uhttps://juser.fz-juelich.de/record/1026489/files/1-s2.0-S0969805123003426-main.pdf$$yRestricted
001026489 8564_ $$uhttps://juser.fz-juelich.de/record/1026489/files/1-s2.0-S0969805123003426-main.gif?subformat=icon$$xicon$$yRestricted
001026489 8564_ $$uhttps://juser.fz-juelich.de/record/1026489/files/1-s2.0-S0969805123003426-main.jpg?subformat=icon-1440$$xicon-1440$$yRestricted
001026489 8564_ $$uhttps://juser.fz-juelich.de/record/1026489/files/1-s2.0-S0969805123003426-main.jpg?subformat=icon-180$$xicon-180$$yRestricted
001026489 8564_ $$uhttps://juser.fz-juelich.de/record/1026489/files/1-s2.0-S0969805123003426-main.jpg?subformat=icon-640$$xicon-640$$yRestricted
001026489 909CO $$ooai:juser.fz-juelich.de:1026489$$pVDB
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)180770$$aForschungszentrum Jülich$$b0$$kFZJ
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)180812$$aForschungszentrum Jülich$$b1$$kFZJ
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)180982$$aForschungszentrum Jülich$$b2$$kFZJ
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)180330$$aForschungszentrum Jülich$$b3$$kFZJ
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)175142$$aForschungszentrum Jülich$$b5$$kFZJ
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)166419$$aForschungszentrum Jülich$$b6$$kFZJ
001026489 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)185610$$aForschungszentrum Jülich$$b7$$kFZJ
001026489 9131_ $$0G:(DE-HGF)POF4-525$$1G:(DE-HGF)POF4-520$$2G:(DE-HGF)POF4-500$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$9G:(DE-HGF)POF4-5253$$aDE-HGF$$bKey Technologies$$lNatural, Artificial and Cognitive Information Processing$$vDecoding Brain Organization and Dysfunction$$x0
001026489 9141_ $$y2024
001026489 920__ $$lyes
001026489 9201_ $$0I:(DE-Juel1)INM-5-20090406$$kINM-5$$lNuklearchemie$$x0
001026489 980__ $$aconf
001026489 980__ $$aVDB
001026489 980__ $$aI:(DE-Juel1)INM-5-20090406
001026489 980__ $$aUNRESTRICTED