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Molecular Probe: Recent Research and Future Challenges
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Molecular Probe: Recent Research and Future Challenges

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (15 June 2024) | Viewed by 10924

Special Issue Editor

Dr. Beatriz Salinas Rodríguez

E-Mail Website
Guest Editor
1. Unidad de Medicina y Cirugía Experimental, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain
2. Departamento de Bioingeniería, Universidad Carlos III de Madrid, 28911 Leganés, Spain
Interests: molecular probes; biomedical imaging; nanomedicine; radiotracers; infectious diseases; cancer; extracellular vesicles; contrast agent

Special Issue Information

Dear Colleagues,

The design and application of new molecular probes is essential for the development of a more specific and selective diagnosis by molecular imaging. The development of new chemical strategies for the labeling of (bio)molecules with radioactive isotopes, the generation of new molecules with optical properties, and the advance of nanotechnology in the creation of new nanoparticles with beneficial physical properties for different imaging techniques have opened a new avenue in the development of non-invasive tools capable of early and specific detection of pathologies as diverse as cancer, neurodegenerative, cardiovascular, and infectious diseases.

In the Special Issue "Molecular Probe: Recent Research and Future Challenges", we welcome your contributions in the form of original research and review articles on all aspects of molecular probes and their biological application through biomedical imaging, as well as articles examining novel chemical methodologies in radioactive or optical labeling, as well as the synthesis of nanoparticles with fluorescent, magnetic or radioactive properties.

Dr. Beatriz Salinas Rodríguez
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • radiotracer
  • probes
  • nanoparticles
  • diagnosis

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Published Papers (6 papers)

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Research

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22 pages, 6865 KiB  
Article
Generic Reporter Sets for Colorimetric Multiplex dPCR Demonstrated with 6-Plex SNP Quantification Panels
by Maximilian Neugebauer, Silvia Calabrese, Sarah Müller, Truong-Tu Truong, Peter Juelg, Nadine Borst, Tobias Hutzenlaub, Eva Dazert, Nikolas Christian Cornelius von Bubnoff, Felix von Stetten and Michael Lehnert
Int. J. Mol. Sci. 2024, 25(16), 8968; https://doi.org/10.3390/ijms25168968 - 17 Aug 2024
Viewed by 986
Abstract
Digital PCR (dPCR) is a powerful method for highly sensitive and precise quantification of nucleic acids. However, designing and optimizing new multiplex dPCR assays using target sequence specific probes remains cumbersome, since fluorescent signals must be optimized for every new target panel. As [...] Read more.
Digital PCR (dPCR) is a powerful method for highly sensitive and precise quantification of nucleic acids. However, designing and optimizing new multiplex dPCR assays using target sequence specific probes remains cumbersome, since fluorescent signals must be optimized for every new target panel. As a solution, we established a generic fluorogenic 6-plex reporter set, based on mediator probe technology, that decouples target detection from signal generation. This generic reporter set is compatible with different target panels and thus provides already optimized fluorescence signals from the start of new assay development. Generic reporters showed high population separability in a colorimetric 6-plex mediator probe dPCR, due to their tailored fluorophore and quencher selection. These reporters were further tested using different KRAS, NRAS and BRAF single-nucleotide polymorphisms (SNP), which are frequent point mutation targets in liquid biopsy. We specifically quantified SNP targets in our multiplex approach down to 0.4 copies per microliter (cp/µL) reaction mix, equaling 10 copies per reaction, on a wild-type background of 400 cp/µL for each, equaling 0.1% variant allele frequencies. We also demonstrated the design of an alternative generic reporter set from scratch in order to give detailed step-by-step guidance on how to systematically establish and optimize novel generic reporter sets. Those generic reporter sets can be customized for various digital PCR platforms or target panels with different degrees of multiplexing. Full article
(This article belongs to the Special Issue Molecular Probe: Recent Research and Future Challenges)
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24 pages, 8102 KiB  
Article
Preclinical Evaluation of a Novel High-Affinity Radioligand [99mTc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA)
by Ekaterina Bezverkhniaia, Panagiotis Kanellopoulos, Ayman Abouzayed, Mariia Larkina, Maryam Oroujeni, Anzhelika Vorobyeva, Ulrika Rosenström, Vladimir Tolmachev and Anna Orlova
Int. J. Mol. Sci. 2023, 24(24), 17391; https://doi.org/10.3390/ijms242417391 - 12 Dec 2023
Cited by 2 | Viewed by 2033
Abstract
Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate [...] Read more.
Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl–triglutamate chelator for labeling with Tc-99m (designated as BQ0413). The purpose of this study was to evaluate the imaging properties of [99mTc]Tc-BQ0413. PSMA-transfected PC3-pip cells were used to evaluate the specificity and affinity of [99mTc]Tc-BQ0413 binding in vitro. PC3-pip tumor-bearing BALB/C nu/nu mice were used as an in vivo model. [99mTc]Tc-BQ0413 bound specifically to PC3-pip cells with an affinity of 33 ± 15 pM. In tumor-bearing mice, the tumor uptake of [99mTc]Tc-BQ0413 (38 ± 6 %IA/g in PC3-pip 3 h after the injection of 40 pmol) was dependent on PSMA expression (3 ± 2 %IA/g and 0.9 ± 0.3 %IA/g in PSMA-negative PC-3 and SKOV-3 tumors, respectively). We show that both unlabeled BQ0413 and the commonly used binder PSMA-11 enable the blocking of [99mTc]Tc-BQ0413 uptake in normal PSMA-expressing tissues without blocking the uptake in tumors. This resulted in an appreciable increase in tumor-to-organ ratios. At the same injected mass (5 nmol), the use of BQ0413 was more efficient in suppressing renal uptake than the use of PSMA-11. In conclusion, [99mTc]Tc-BQ0413 is a promising probe for the visualization of PSMA-positive lesions using single-photon emission computed tomography (SPECT). Full article
(This article belongs to the Special Issue Molecular Probe: Recent Research and Future Challenges)
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10 pages, 1380 KiB  
Article
Fully Automated Production of [68Ga]GaFAPI-46 with Gallium-68 from Cyclotron Using Liquid Targets
by Alexandra I. Fonseca, Vítor H. Alves, Ivanna Hrynchak, Francisco Alves and Antero J. Abrunhosa
Int. J. Mol. Sci. 2023, 24(20), 15101; https://doi.org/10.3390/ijms242015101 - 12 Oct 2023
Viewed by 1368
Abstract
68Ga-based radiopharmaceuticals are routinely used for PET imaging of multiple types of tumors. Gallium-68 is commonly obtained from 68Ge/68Ga generators, which are limited in the quantity of activity produced. Alternatively, gallium-68 can easily be produced on a cyclotron using [...] Read more.
68Ga-based radiopharmaceuticals are routinely used for PET imaging of multiple types of tumors. Gallium-68 is commonly obtained from 68Ge/68Ga generators, which are limited in the quantity of activity produced. Alternatively, gallium-68 can easily be produced on a cyclotron using liquid targets. In this study, we optimized the GMP production of [68Ga]GaFAPI-46 using gallium-68 produced via a standard medical cyclotron using liquid targets. Starting from the published synthesis and quality control procedures described for other 68Ga-based radiopharmaceuticals, we have validated the synthesis process and the analytical methods to test the quality parameters of the final product to be used for routine clinical studies. [68Ga]GaFAPI-46 was successfully produced with high radiochemical purity and yield using an IBA Synthera® Extension module. Gallium chloride was produced on a medical cyclotron using a liquid target with activity of 4.31 ± 0.36 GBq at the end of purification (EOP). Analytical methods were established and validated, meeting Ph. Eur. standards. Full GMP production was also validated in three consecutive batches, producing 2.50 ± 0.46 GBq of [68Ga]GaFAPI-46 at the end of synthesis (EOS), with 98.94 ± 0.72% radiochemical purity measured via radio-HPLC. Quality was maintained for up to 3 h after the EOS. Production of [68Ga]GaFAPI-46 was performed and validated using a standard medical cyclotron with liquid targets. The quality control parameters (e.g., sterility, purity, and residual solvents) conformed to Ph. Eur. and a shelf life of 3 h was established. The activity of [68Ga]GaFAPI-46 produced was substantially higher than the one obtained with generators, enabling a better response to the clinical need for this radiopharmaceutical. Full article
(This article belongs to the Special Issue Molecular Probe: Recent Research and Future Challenges)
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Review

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12 pages, 2371 KiB  
Review
Applications of SPECT and PET Imaging for the Physiological Evaluation of Lower Extremity Peripheral Artery Disease
by Eleanor T. Rimmerman and Mitchel R. Stacy
Int. J. Mol. Sci. 2024, 25(13), 7474; https://doi.org/10.3390/ijms25137474 - 8 Jul 2024
Viewed by 1238
Abstract
Peripheral artery disease (PAD) is classified as the narrowing or complete occlusion of the lower extremity arteries due to atherosclerosis. The risk of developing PAD increases with increased age and risk factors such as smoking, diabetes, hypertension, and hypercholesterolemia. Current treatment for PAD [...] Read more.
Peripheral artery disease (PAD) is classified as the narrowing or complete occlusion of the lower extremity arteries due to atherosclerosis. The risk of developing PAD increases with increased age and risk factors such as smoking, diabetes, hypertension, and hypercholesterolemia. Current treatment for PAD involves lifestyle and symptom management, statin and antiplatelet therapy, and/or surgical interventions to improve quality of life with varying efficacy. PAD affects approximately 5 to 6 percent of the global population, with this global burden continuing to increase. Despite the increase in disease prevalence, no gold standard functional diagnostic tool has been established for enabling early detection of the disease, appropriate medical management, and prediction of adverse outcomes for PAD patients. The visualization and quantification of the physiological consequences of PAD are possible by way of nuclear imaging: specifically, via scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging. These non-invasive modalities, when combined with targeted radionuclides, possess utility for detecting functional perfusion deficits and provide unique insight into muscle tissue- and vascular-level characteristics of PAD patients. This review discusses the past, present, and emerging applications of hybrid nuclear imaging modalities in the evaluation and monitoring of patients with PAD. Full article
(This article belongs to the Special Issue Molecular Probe: Recent Research and Future Challenges)
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37 pages, 6614 KiB  
Review
Hyperpolarized Xenon-129 Chemical Exchange Saturation Transfer (HyperCEST) Molecular Imaging: Achievements and Future Challenges
by Viktoriia Batarchuk, Yurii Shepelytskyi, Vira Grynko, Antal Halen Kovacs, Aaron Hodgson, Karla Rodriguez, Ruba Aldossary, Tanu Talwar, Carson Hasselbrink, Iulian C. Ruset, Brenton DeBoef and Mitchell S. Albert
Int. J. Mol. Sci. 2024, 25(3), 1939; https://doi.org/10.3390/ijms25031939 - 5 Feb 2024
Cited by 1 | Viewed by 2312
Abstract
Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) 129Xe biosensors have been recently [...] Read more.
Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) 129Xe biosensors have been recently developed, demonstrating their potential applications in molecular settings, and achieving notable success within in vitro studies. The favorable nuclear magnetic resonance properties of 129Xe, coupled with its non-toxic nature, high solubility in biological tissues, and capacity to dissolve in blood and diffuse across membranes, highlight its superior role for applications in molecular MRI settings. The incorporation of reporters that combine signal enhancement from both hyperpolarized 129Xe and chemical exchange saturation transfer holds the potential to address the primary limitation of low sensitivity observed in conventional MRI. This review provides a summary of the various applications of HP 129Xe biosensors developed over the last decade, specifically highlighting their use in MRI. Moreover, this paper addresses the evolution of in vivo applications of HP 129Xe, discussing its potential transition into clinical settings. Full article
(This article belongs to the Special Issue Molecular Probe: Recent Research and Future Challenges)
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26 pages, 10135 KiB  
Review
Bisphosphonates as Radiopharmaceuticals: Spotlight on the Development and Clinical Use of DOTAZOL in Diagnostics and Palliative Radionuclide Therapy
by Céleste Souche, Juliette Fouillet, Léa Rubira, Charlotte Donzé, Emmanuel Deshayes and Cyril Fersing
Int. J. Mol. Sci. 2024, 25(1), 462; https://doi.org/10.3390/ijms25010462 - 29 Dec 2023
Viewed by 1862
Abstract
Bisphosphonates are therapeutic agents that have been used for almost five decades in the treatment of various bone diseases, such as osteoporosis, Paget disease and prevention of osseous complications in cancer patients. In nuclear medicine, simple bisphosphonates such as 99mTc-radiolabelled oxidronate and [...] Read more.
Bisphosphonates are therapeutic agents that have been used for almost five decades in the treatment of various bone diseases, such as osteoporosis, Paget disease and prevention of osseous complications in cancer patients. In nuclear medicine, simple bisphosphonates such as 99mTc-radiolabelled oxidronate and medronate remain first-line bone scintigraphic imaging agents for both oncology and non-oncology indications. In line with the growing interest in theranostic molecules, bifunctional bisphosphonates bearing a chelating moiety capable of complexing a variety of radiometals were designed. Among them, DOTA-conjugated zoledronate (DOTAZOL) emerged as an ideal derivative for both PET imaging (when radiolabeled with 68Ga) and management of bone metastases from various types of cancer (when radiolabeled with 177Lu). In this context, this report provides an overview of the main medicinal chemistry aspects concerning bisphosphonates, discussing their roles in molecular oncology imaging and targeted radionuclide therapy with a particular focus on bifunctional bisphosphonates. Particular attention is also paid to the development of DOTAZOL, with emphasis on the radiochemistry and quality control aspects of its preparation, before outlining the preclinical and clinical data obtained so far with this radiopharmaceutical candidate. Full article
(This article belongs to the Special Issue Molecular Probe: Recent Research and Future Challenges)
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