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001027702 1001_ $$0P:(DE-Juel1)186668$$aStrecker, Jonas$$b0$$ufzj
001027702 1112_ $$a24th International Symposium on Radiopharmaceutical Sciences$$cNantes$$d2022-05-29 - 2022-06-03$$gISRS2022$$wFrance
001027702 245__ $$a52gMn(II)-Labelled PSMA-ligands as bimodal PET/MR imaging probes
001027702 260__ $$c2022
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001027702 520__ $$aIntroduction: By combining the advantages of two or more complementaryimaging modalities, hybrid techniques like PET/MR allowfor sequential or simultaneous acquisition of anatomical and molecularinformation. Although the alignment of hybrid datasets acquiredin simultaneous PET/MR has been shown to be more accurate, thereis still a lack of probes for bimodal PET/MR imaging. Radiolabellingwith isotopic mixtures of 52gMn/55Mn provides direct access to suchprobes1,2, as the paramagnetic 55Mn acts as an MRI contrast agent3,while 52gMn is a promising +-emitter for PET imaging (t½ = 5.6 d, E+,end = 0,58 MeV). In the present work, the PSMA-selective moiety Glu-C(O)-Lys was functionalized by CuAAC click reaction with the chelatortrans-1,2-diaminocyclohexane-N,N,N`,N`-tetraacetic acid (CDTA)for Mn complexation and radiolabeling with 52gMn. In addition, thestability of the novel PET/MR probe was evaluated by preliminary invitro studies.Materials and Methods: Following its production by the52Cr(p,n)52gMn nuclear reaction, 52gMn was separated from the Crtarget using anion exchange chromatography. To this end, the Crtarget was dissolved in 2 m HCl, which was then evaporated todryness. The residue was dissolved in MeOH/conc. HAc (1:1) andtrapped on an AG-MP1 anion exchange column. The column waswashed with 30 mL MeOH/conc. HAc. (1:1) at 44°C and [52gMn]MnCl2was eluted with 3 m HCl.The CDTA ligand was synthesized using a modification of a previouslypublished method4 and coupled to the PSMA-selective Glu-C(O)-Lys pharmacophore by the copper(I)-catalyzed alkyne-azidecycloaddition (CuAAC) click reaction.The functionalized CDTA-ligand (2.5 mg) was dissolved in 0.1 mNaOAc buffer (pH 6) and treated with no-carrier added [52gMn]MnCl2for 30 min at ambient temperature, and the radiolabelled productwas subsequently isolated by HPLC.The stability of the PET/MR probe in the presence of human serumwas measured in HBS buffer at 37°C and analysed by HPLC.Results and Conclusion: No-carrier added 52gMn was isolatedfrom the Cr target with a separation yield of 93%. An improved labellingprotocol for the CDTA functionalized PSMA-selective ligand wasestablished, yielding a radiochemical yield of 50 % (based on HPLCanalysis of the crude product). After 24 h, 28.2% of the complex wasstill intact justifying further evaluation by in vivo animal studies.References:[1] Thomas G. et al. Innovative Magnetic Nanoparticles for PET/MRIBimodal Imaging. ACS Omega. 2019, 4, 2637-2648[2] de Rosales R.T.M. Potential clinical applications of bimodalPET-MRI or SPECT-MRI agents J. Label Compd. Radiopharm. 2014,57, 298–303[3] Glover, P., Mansfield, S. P. Limits to magnetic resonance microscopy.Reports Prog. Phys. 2002, 65, 1489.[4] Vanasschen, C., Brandt, M., Ermert, J., Coenen, H. H. Radiolabellingwith isotopic mixtures of 52g/55Mn(II) as a straight route to stablemanganese complexes for bimodal PET/MR imaging. Dalt. Trans.2016, 45, 1315–1321.
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001027702 7001_ $$0P:(DE-Juel1)131849$$aSpahn, Ingo$$b1$$ufzj
001027702 7001_ $$0P:(DE-Juel1)166419$$aNeumaier, Bernd$$b2$$eCorresponding author$$ufzj
001027702 7001_ $$0P:(DE-Juel1)171718$$aGiesen, Kai$$b3
001027702 7001_ $$0P:(DE-HGF)0$$aGülez, Salim$$b4
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