Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.7
4.6
Journals
Pharmaceuticals
Special Issues
Hybrid Agents for Multimodal Imaging
share announcement

Hybrid Agents for Multimodal Imaging

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Radiopharmaceutical Sciences".

Deadline for manuscript submissions: closed (25 February 2022) | Viewed by 18052

Special Issue Editors

Prof. Dr. Carmen Wängler

E-Mail Website1 Website2
Guest Editor
Biomedical Chemistry, Clinic of Radiology and Nuclear Medicine, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany
Interests: radiotracer development; multimodal imaging; radiolabeling strategies; target-specific imaging
Special Issues, Collections and Topics in MDPI journals
Dr. Ralph Hübner

E-Mail Website
Guest Editor
Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Interests: multimodal imaging; optical imaging; theranostic; radiotracer

Special Issue Information

Dear Colleagues,

The journal Pharmaceuticals is planning to publish a Special Issue, Hybrid Agents for Multimodal Imaging, and I am cordially inviting you to contribute an article to this volume, describing your latest research and, of course, reviews are welcome as well.

The use of imaging to visualize and characterize a wide variety of diseases is deeply embedded in routine clinical practice. In addition to conventional imaging, the combination of imaging modalities is of increasing relevance and an increasing number of complementary combinations are being used to the benefit of patients. For this reason, a growing field of research has been focusing for several years on the development of combined or combinable contrast agents that can be detected using multiple imaging modalities, thus allowing a complementary gain of information.

The goal of this Special Issue is to gather the latest developments in this area of hybrid imaging agent development for multimodal imaging to provide the most complete coverage of this exciting and forward-looking area of research.

Prof. Dr. Carmen Wängler
Dr. Ralph Hübner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hybrid contrast agents
  • molecular imaging
  • hybrid imaging
  • precision medicine
  • computed tomography
  • magnetic resonance imaging
  • optical imaging
  • photoacoustic imaging
  • positron emission tomography
  • single-photon emission computed tomography

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 9862 KiB  
Article
A New Class of PSMA-617-Based Hybrid Molecules for Preoperative Imaging and Intraoperative Fluorescence Navigation of Prostate Cancer
by Ann-Christin Eder, Jessica Matthias, Martin Schäfer, Jana Schmidt, Nils Steinacker, Ulrike Bauder-Wüst, Lisa-Charlotte Domogalla, Mareike Roscher, Uwe Haberkorn, Matthias Eder and Klaus Kopka
Pharmaceuticals 2022, 15(3), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15030267 - 22 Feb 2022
Cited by 1 | Viewed by 2967
Abstract
The development of PSMA-targeting low-molecular-weight hybrid molecules aims at advancing preoperative imaging and accurate intraoperative fluorescence guidance for improved diagnosis and therapy of prostate cancer. In hybrid probe design, the major challenge is the introduction of a bulky dye to peptidomimetic core structures [...] Read more.
The development of PSMA-targeting low-molecular-weight hybrid molecules aims at advancing preoperative imaging and accurate intraoperative fluorescence guidance for improved diagnosis and therapy of prostate cancer. In hybrid probe design, the major challenge is the introduction of a bulky dye to peptidomimetic core structures without affecting tumor-targeting properties and pharmacokinetic profiles. This study developed a novel class of PSMA-targeting hybrid molecules based on the clinically established theranostic agent PSMA-617. The fluorescent dye-bearing candidates of the strategically designed molecule library were evaluated in in vitro assays based on their PSMA-binding affinity and internalization properties to identify the most favorable hybrid molecule composition for the installation of a bulky dye. The library’s best candidate was realized with IRDye800CW providing the lead compound. Glu-urea-Lys-2-Nal-Chx-Lys(IRDye800CW)-DOTA (PSMA-927) was investigated in an in vivo proof-of-concept study, with compelling performance in organ distribution studies, PET/MRI and optical imaging, and with a strong PSMA-specific tumor uptake comparable to that of PSMA-617. This study provides valuable insights about the design of PSMA-targeting low-molecular-weight hybrid molecules, which enable further advances in the field of peptidomimetic hybrid molecule development. Full article
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
►▼ Show Figures

Graphical abstract

19 pages, 4107 KiB  
Article
Radiolabeled Silicon-Rhodamines as Bimodal PET/SPECT-NIR Imaging Agents
by Thines Kanagasundaram, Markus Laube, Johanna Wodtke, Carsten Sven Kramer, Sven Stadlbauer, Jens Pietzsch and Klaus Kopka
Pharmaceuticals 2021, 14(11), 1155; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14111155 - 12 Nov 2021
Cited by 5 | Viewed by 3779
Abstract
Radiolabeled fluorescent dyes are decisive for bimodal imaging as well as highly in demand for nuclear- and optical imaging. Silicon-rhodamines (SiRs) show unique near-infrared (NIR) optical properties, large quantum yields and extinction coefficients as well as high photostability. Here, we describe the synthesis, [...] Read more.
Radiolabeled fluorescent dyes are decisive for bimodal imaging as well as highly in demand for nuclear- and optical imaging. Silicon-rhodamines (SiRs) show unique near-infrared (NIR) optical properties, large quantum yields and extinction coefficients as well as high photostability. Here, we describe the synthesis, characterization and radiolabeling of novel NIR absorbing and emitting fluorophores from the silicon-rhodamine family for use in optical imaging (OI) combined with positron emission tomography (PET) or single photon emission computed tomography (SPECT), respectively. The presented photostable SiRs were characterized using NMR-, UV-Vis-NIR-spectroscopy and mass spectrometry. Moreover, the radiolabeling conditions using fluorine-18 or iodine-123 were extensively explored. After optimization, the radiofluorinated NIR imaging agents were obtained with radiochemical conversions (RCC) up to 70% and isolated radiochemical yields (RCY) up to 54% at molar activities of g.t. 70 GBq/µmol. Radioiodination delivered RCCs over 92% and allowed to isolate the 123I-labeled product in RCY of 54% at a molar activity of g.t. 7.6 TBq/µmol. The radiofluorinated SiRs exhibit in vitro stabilities g.t. 70% after two hours in human serum. The first described radiolabeled SiRs are a promising step toward their further development as multimodal PET/SPECT-NIR imaging agents for planning and subsequent imaging-guided oncological surgery. Full article
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
►▼ Show Figures

Graphical abstract

17 pages, 3367 KiB  
Article
Development and Characterisation of Antibody-Based Optical Imaging Probes for Inflammatory Bowel Disease
by Matthijs David Linssen, Wouter Tjerk Rudolph Hooghiemstra, Annelies Jorritsma-Smit, Derk Pieter Allersma, Gerard Dijkstra and Wouter Bastiaan Nagengast
Pharmaceuticals 2021, 14(9), 922; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090922 - 13 Sep 2021
Cited by 4 | Viewed by 2589
Abstract
Monoclonal antibodies are an important addition to the medicinal treatment paradigm for IBD patients. While effective, these agents show a high degree of primary and secondary non-response, and methods to predict response are highly desired. Information on drug distribution at the target level [...] Read more.
Monoclonal antibodies are an important addition to the medicinal treatment paradigm for IBD patients. While effective, these agents show a high degree of primary and secondary non-response, and methods to predict response are highly desired. Information on drug distribution at the target level is often lacking. Fluorescent endoscopic imaging using labelled antibody drugs may provide insight regarding drug distribution, target engagement and drug response, but these assessments require stable and functional fluorescently-conjugated probes. Infliximab, vedolizumab, adalimumab and ustekinumab were conjugated to IRDye 800CW, IRDye 680LT and ZW800-1. The resulting 12 tracer candidates were analysed and characterised on SE-HPLC, SDS-PAGE, iso-electric focussing (IEF) and ELISA in order to evaluate their feasibility as candidate clinical tracers for cGMP development. Major differences in the conjugation results could be seen for each conjugated drug. For Infliximab, 2 conjugates (800CW and 680LT) showed formation of aggregates, while conjugates of all drugs with ZW800-1 showed reduced fluorescent brightness, reduced purification yield and formation of fragments. All 6 of these candidates were considered unfeasible. From the remaining 6, ustekinumab-680LT showed reduced binding to IL23, and was therefore considered unfeasible. Out of 12 potential tracer candidates, 5 were considered feasible for further development: vedolizumab-800CW, vedolizumab-680LT, adalimumab-800CW, adalimumab-680LT and ustekinumab-800CW. Infliximab-680LT and ustekinumab-680LT failed to meet the standards for this panel, but may be rendered feasible if tracer production methods were further optimized. Full article
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
►▼ Show Figures

Figure 1

14 pages, 2887 KiB  
Article
PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study
by Ralph Hübner, 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
Pharmaceuticals 2021, 14(6), 531; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060531 - 02 Jun 2021
Cited by 3 | Viewed by 2675
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
►▼ Show Figures

Figure 1

Review

Jump to: Research

27 pages, 5779 KiB  
Review
Dual-Labelling Strategies for Nuclear and Fluorescence Molecular Imaging: Current Status and Future Perspectives
by Manja Kubeil, Irma Ivette Santana Martínez, Michael Bachmann, Klaus Kopka, Kellie L. Tuck and Holger Stephan
Pharmaceuticals 2022, 15(4), 432; https://0-doi-org.brum.beds.ac.uk/10.3390/ph15040432 - 31 Mar 2022
Cited by 8 | Viewed by 3305
Abstract
Molecular imaging offers the possibility to investigate biological and biochemical processes non-invasively and to obtain information on both anatomy and dysfunctions. Based on the data obtained, a fundamental understanding of various disease processes can be derived and treatment strategies can be planned. In [...] Read more.
Molecular imaging offers the possibility to investigate biological and biochemical processes non-invasively and to obtain information on both anatomy and dysfunctions. Based on the data obtained, a fundamental understanding of various disease processes can be derived and treatment strategies can be planned. In this context, methods that combine several modalities in one probe are increasingly being used. Due to the comparably high sensitivity and provided complementary information, the combination of nuclear and optical probes has taken on a special significance. In this review article, dual-labelled systems for bimodal nuclear and optical imaging based on both modular ligands and nanomaterials are discussed. Particular attention is paid to radiometal-labelled molecules for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) and metal complexes combined with fluorescent dyes for optical imaging. The clinical potential of such probes, especially for fluorescence-guided surgery, is assessed. Full article
(This article belongs to the Special Issue Hybrid Agents for Multimodal Imaging)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop