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Self-assembling peptide based system for detection of enzymatic activity by means of MRI

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Keliris,  A
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Engelmann,  J
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Hagberg,  GE
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Scheffler,  K
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Keliris, A., Engelmann, J., Hagberg, G., & Scheffler, K. (2015). Self-assembling peptide based system for detection of enzymatic activity by means of MRI. Poster presented at 10th Annual Meeting of the European Society for Molecular Imaging (EMIM 2015), Tübingen, Germany.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-4724-4
Abstract
Introduction Noninvasive mapping of enzyme activity by means of MRI holds a great potential for improved diagnostics of diseases and evaluation of cell therapies [1]. Controlled self-assembly of low molecular weight Gd(III) complexes into large aggregates is an efficient approach for delivering enzyme activatable MRI contrast agents. Herein, we report on peptide based self-assembling conjugates for the detection of carboxypeptidase B (CPB) activity by means of 1H MRI. Methods Gd(III)-peptide conjugate (Gd-PE) and unlabelled peptides (PEs) were obtained by utilizing Fmoc/Boc solid-phase synthetic scheme. Relaxation rates R1 and R2 of these conjugates in TRIS buffer (pH=7.6) were measured at a 3T MR system (~25°C) in the presence and absence of carboxypeptidase B. Corresponding T1-and T2-weighted MR images were acquired as well. In addition enzyme kinetics were assessed by ESI-MS. Results Gd-PE and PEs with a CPB cleavable sequence masking the self-assembling moiety were synthesized in a high yield. Their structure was verified by ESI-MS. Longitudinal and transverse relaxivity of Gd-PE were found to be 12.8±0.1 mM−1 s−1 and 27.7 ±0.1 mM−1 s−1, respectively, and thus were much higher compared to commercial agents (r1~ 4 mM−1 s−1). Upon enzymatic conversion of Gd-PE, the released molecules assembled into Gd-aggregates to result in marked changes of proton relaxation rates of ~17 for R1 and ~32 for R2. The observed changes were even larger when Gd-PE was mixed with PEs reaching ~36 in R1 and up to ~150 in R2. A strong contrast enhancement was observed for these samples in T1- and T2-weighted MR images. The conversion of Gd-PE by CPB in a time dependent manner was confirmed by ESI-MS.