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Recent Advances and Future Trends in Molecular Imaging

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Photochemistry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 6443

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Special Issue Editor

Dr. David Brasse

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Guest Editor

Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg, Strasbourg, France
Interests: molecular imaging; positron emission tomography; instrumentation; image reconstruction; preclinical studies

Special Issue Information

Dear Colleagues,

“A century ago, the living body, like most of the material world, was opaque. Then Wilhelm Roentgen captured an X-ray image of his wife’s finger – her wedding ring “floating” around a white bone – and our range of vision changed forever”. From the words of Bettyann Holtzmann Kelves up to now, amazing progresses have been made in medical imaging.

From nuclear medicine to molecular imaging, radiotracers were used in conjunction with imaging technologies to observe complex biological processes at the early stage of the disease or for therapeutic follow-ups. Nowadays, this research area integrates a plethora of contrast agents with the utilization of a variety of additional imaging modalities, such as optical bioimaging, magnetic resonance imaging, and ultrasound imaging.

The last twenty years, considerable research efforts have been focused in the synthesis and validation of labeling probes or contrast agents, the development of molecular imaging instrumentation, and the development of algorithm and software tools for the reconstruction, the visualization and the analysis of molecular imaging data. However, many difficult challenges remain. Discussing these challenges in detail and illustrating recent progress and future directions, this Special Issue will collect high-quality, peer-reviewed, original research papers in the area of molecular imaging.

Dr. David Brasse
Guest Editor

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

molecular imaging
translational research
multimodal approach
artificial intelligence
drug development
radiolabeling
new detector design

Published Papers (4 papers)

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Research

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13 pages, 1809 KiB

Open AccessArticle

Antibody and Nanobody Radiolabeling with Copper-64: Solid vs. Liquid Target Approach

by Ivanna Hrynchak, Diana Cocioabă, Alexandra I. Fonseca, Radu Leonte, Sérgio J. C. do Carmo, Roxana Cornoiu, Amílcar Falcão, Dana Niculae and Antero J. Abrunhosa

Molecules 2023, 28(12), 4670; https://doi.org/10.3390/molecules28124670 - 09 Jun 2023

Cited by 2 | Viewed by 1504

Abstract

Antibody and nanobody-based copper-64 radiopharmaceuticals are increasingly being proposed as theranostic tools in multiple human diseases. While the production of copper-64 using solid targets has been established for many years, its use is limited due to the complexity of solid target systems, which are available in only a few cyclotrons worldwide. In contrast, liquid targets, available in virtually in all cyclotrons, constitute a practical and reliable alternative. In this study, we discuss the production, purification, and radiolabeling of antibodies and nanobodies using copper-64 obtained from both solid and liquid targets. Copper-64 production from solid targets was performed on a TR-19 cyclotron with an energy of 11.7 MeV, while liquid target production was obtained by bombarding a nickel-64 solution using an IBA Cyclone Kiube cyclotron with 16.9 MeV on target. Copper-64 was purified from both solid and liquid targets and used to radiolabel NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab conjugates. Stability studies were conducted on all radioimmunoconjugates in mouse serum, PBS, and DTPA. Irradiation of the solid target yielded 13.5 ± 0.5 GBq with a beam current of 25 ± 1.2 μA and an irradiation time of 6 h. On the other hand, irradiation of the liquid target resulted in 2.8 ± 1.3 GBq at the end of bombardment (EOB) with a beam current of 54.5 ± 7.8 μA and an irradiation time of 4.1 ± 1.3 h. Successful radiolabeling of NODAGA-Nb, NOTA-Nb, and DOTA-Trastuzumab with copper-64 from both solid and liquid targets was achieved. Specific activities (SA) obtained with the solid target were 0.11, 0.19, and 0.33 MBq/μg for NODAGA-Nb, NOTA-Nb, and DOTA-trastuzumab, respectively. For the liquid target, the corresponding SA values were 0.15, 0.12, and 0.30 MBq/μg. Furthermore, all three radiopharmaceuticals demonstrated stability under the testing conditions. While solid targets have the potential to produce significantly higher activity in a single run, the liquid process offers advantages such as speed, ease of automation, and the feasibility of back-to-back production using a medical cyclotron. In this study, successful radiolabeling of antibodies and nanobodies was achieved using both solid and liquid targets approaches. The radiolabeled compounds exhibited high radiochemical purity and specific activity, rendering them suitable for subsequent in vivo pre-clinical imaging studies. Full article

(This article belongs to the Special Issue Recent Advances and Future Trends in Molecular Imaging)

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14 pages, 2769 KiB

Open AccessArticle

Synthesis and Evaluation of ⁶⁸Ga-Labeled (2S,4S)-4-Fluoropyrrolidine-2-Carbonitrile and (4R)-Thiazolidine-4-Carbonitrile Derivatives as Novel Fibroblast Activation Protein-Targeted PET Tracers for Cancer Imaging

by Shreya Bendre, Zhengxing Zhang, Nadine Colpo, Jutta Zeisler, Antonio A. W. L. Wong, François Bénard and Kuo-Shyan Lin

Molecules 2023, 28(8), 3481; https://doi.org/10.3390/molecules28083481 - 14 Apr 2023

Cited by 2 | Viewed by 1693

Abstract

Fibroblast activation protein α (FAP-α) is a cell-surface protein overexpressed on cancer-associated fibroblasts that constitute a substantial component of tumor stroma and drive tumorigenesis. FAP is minimally expressed by most healthy tissues, including normal fibroblasts. This makes it a promising pan-cancer diagnostic and therapeutic target. In the present study, we synthesized two novel tracers, [⁶⁸Ga]Ga-SB03045 and [⁶⁸Ga]Ga-SB03058, bearing a (2S,4S)-4-fluoropyrrolidine-2-carbonitrile or a (4R)-thiazolidine-4-carbonitrile pharmacophore, respectively. [⁶⁸Ga]Ga-SB03045 and [⁶⁸Ga]Ga-SB03058 were evaluated for their FAP-targeting capabilities using substrate-based in vitro binding assays, and in PET/CT imaging and ex vivo biodistribution studies in an HEK293T:hFAP tumor xenograft mouse model. The IC₅₀ values of ^natGa-SB03045 (1.59 ± 0.45 nM) and ^natGa-SB03058 (0.68 ± 0.09 nM) were found to be lower than those of the clinically validated ^natGa-FAPI-04 (4.11 ± 1.42 nM). Contrary to the results obtained in the FAP-binding assay, [⁶⁸Ga]Ga-SB03058 demonstrated a ~1.5 fold lower tumor uptake than that of [⁶⁸Ga]Ga-FAPI-04 (7.93 ± 1.33 vs. 11.90 ± 2.17 %ID/g), whereas [⁶⁸Ga]Ga-SB03045 (11.8 ± 2.35 %ID/g) exhibited a tumor uptake comparable to that of [⁶⁸Ga]Ga-FAPI-04. Thus, our data suggest that the (2S,4S)-4-fluoropyrrolidine-2-carbonitrile scaffold holds potential as a promising pharmacophore for the design of FAP-targeted radioligands for cancer diagnosis and therapy. Full article

(This article belongs to the Special Issue Recent Advances and Future Trends in Molecular Imaging)

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Review

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18 pages, 2573 KiB

Open AccessReview

Scandium Radioisotopes—Toward New Targets and Imaging Modalities

by Krzysztof Kilian and Krystyna Pyrzyńska

Molecules 2023, 28(22), 7668; https://doi.org/10.3390/molecules28227668 - 19 Nov 2023

Cited by 3 | Viewed by 992

Abstract

The concept of theranostics uses radioisotopes of the same or chemically similar elements to label biological ligands in a way that allows the use of diagnostic and therapeutic radiation for a combined diagnosis and treatment regimen. For scandium, radioisotopes -43 and -44 can be used as diagnostic markers, while radioisotope scandium-47 can be used in the same configuration for targeted therapy. This work presents the latest achievements in the production and processing of radioisotopes and briefly characterizes solutions aimed at increasing the availability of these radioisotopes for research and clinical practice. Full article

(This article belongs to the Special Issue Recent Advances and Future Trends in Molecular Imaging)

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32 pages, 18243 KiB

Open AccessReview

New Advances in the Exploration of Esterases with PET and Fluorescent Probes

by Alba Gil-Rivas, Beatriz de Pascual-Teresa, Irene Ortín and Ana Ramos

Molecules 2023, 28(17), 6265; https://doi.org/10.3390/molecules28176265 - 27 Aug 2023

Cited by 1 | Viewed by 1599

Abstract

Esterases are hydrolases that catalyze the hydrolysis of esters into the corresponding acids and alcohols. The development of fluorescent probes for detecting esterases is of great importance due to their wide spectrum of biological and industrial applications. These probes can provide a rapid and sensitive method for detecting the presence and activity of esterases in various samples, including biological fluids, food products, and environmental samples. Fluorescent probes can also be used for monitoring the effects of drugs and environmental toxins on esterase activity, as well as to study the functions and mechanisms of these enzymes in several biological systems. Additionally, fluorescent probes can be designed to selectively target specific types of esterases, such as those found in pathogenic bacteria or cancer cells. In this review, we summarize the recent fluorescent probes described for the visualization of cell viability and some applications for in vivo imaging. On the other hand, positron emission tomography (PET) is a nuclear-based molecular imaging modality of great value for studying the activity of enzymes in vivo. We provide some examples of PET probes for imaging acetylcholinesterases and butyrylcholinesterases in the brain, which are valuable tools for diagnosing dementia and monitoring the effects of anticholinergic drugs on the central nervous system. Full article

(This article belongs to the Special Issue Recent Advances and Future Trends in Molecular Imaging)

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