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Article

PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study

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Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
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Institute of Inorganic Chemistry, University Stuttgart, Pfaffenwaldring 55, 70550 Stuttgart, Germany
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Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
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Department of Pharmaceutical Sciences, Medicinal Chemistry Section “Pietro Pratesi”, University of Milan, Via L. Mangiagalli 25, 20133 Milan, Italy
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Department of Oncology, Division of Oncological Imaging, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada
*
Authors to whom correspondence should be addressed.
Dedicated to Professor Wolfgang Kaim on the Occasion of his 70th Birthday.
Academic Editor: Gerald Reischl
Pharmaceuticals 2021, 14(6), 531; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060531
Received: 26 April 2021 / Revised: 27 May 2021 / Accepted: 28 May 2021 / Published: 2 June 2021
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
Recently, anionic charges were found to negatively influence the in vitro gastrin-releasing peptide receptor (GRPR) binding parameters of dually radioisotope and fluorescent dye labeled GRPR-specific peptide dimers. From this, the question arose if this adverse impact on in vitro GRP receptor affinities could be mitigated by a higher valency of peptide multimerization. For this purpose, we designed two different hybrid multimodal imaging units (MIUs), comprising either one or two click chemistry-compatible functional groups and reacted them with PESIN (PEG3-BBN7–14, PEG = polyethylene glycol) dimers to obtain a dually labeled peptide homodimer or homotetramer. Using this approach, other dually labeled peptide monomers, dimers, and tetramers can also be obtained, and the chelator and fluorescent dye can be adapted to specific requirements. The MIUs, as well as their peptidic conjugates, were evaluated in terms of their photophysical properties, radiolabeling efficiency with 68Ga and 64Cu, hydrophilicity, and achievable GRP receptor affinities. Here, the hydrophilicity and the GRP receptor binding affinities were found to be especially strongly influenced by the number of negative charges and peptide copies, showing logD (1-octanol-water-distribution coefficient) and IC50 (half maximal inhibitory concentration) values of −2.2 ± 0.1 and 59.1 ± 1.5 nM for the homodimer, and −1.9 ± 0.1 and 99.8 ± 3.2 nM for the homotetramer, respectively. From the obtained data, it can be concluded that the adverse influence of negatively charged building blocks on the in vitro GRP receptor binding properties of dually labeled PESIN multimers can, at least partly, be compensated for by the number of introduced peptide binding motives and the used molecular design. View Full-Text
Keywords: cell binding; copper-64; gallium-68; GRPR affinity; indocyanine dyes; multimodal imaging; NIR fluorescent dyes; PESIN multimers cell binding; copper-64; gallium-68; GRPR affinity; indocyanine dyes; multimodal imaging; NIR fluorescent dyes; PESIN multimers
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MDPI and ACS Style

Hübner, R.; Paretzki, A.; von Kiedrowski, V.; Maspero, M.; Cheng, X.; Davarci, G.; Braun, D.; Damerow, H.; Judmann, B.; Filippou, V.; Dallanoce, C.; Schirrmacher, R.; Wängler, B.; Wängler, C. PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study. Pharmaceuticals 2021, 14, 531. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060531

AMA Style

Hübner R, Paretzki A, von Kiedrowski V, Maspero M, Cheng X, Davarci G, Braun D, Damerow H, Judmann B, Filippou V, Dallanoce C, Schirrmacher R, Wängler B, Wängler C. PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study. Pharmaceuticals. 2021; 14(6):531. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060531

Chicago/Turabian Style

Hübner, Ralph, Alexa Paretzki, Valeska von Kiedrowski, Marco Maspero, Xia Cheng, Güllü Davarci, Diana Braun, Helen Damerow, Benedikt Judmann, Vasileios Filippou, Clelia Dallanoce, Ralf Schirrmacher, Björn Wängler, and Carmen Wängler. 2021. "PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study" Pharmaceuticals 14, no. 6: 531. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060531

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