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Recent Advances in Techniques with Radionuclide for Theranostic Drugs

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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 (15 December 2021) | Viewed by 15543

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Special Issue Editors

Prof. Dr. Kazuma Ogawa

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Guest Editor

Discovering Molecular Probes Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
Interests: theranostics; radiolabeling; radiopharmaceuticals; molecular imaging; cancer; radionuclide therapy; radiosynthesis

Dr. Shigeki Watanabe

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Guest Editor

Department of Radiation-Applied Biology, Takasaki Advanced Radiation Research Institute, National Institutes for Quantum and Radiological Science and Technology (QST), Watanuki-machi, Takasaki, Gunma 370-1292, Japan
Interests: radionuclide production; radionuclide separation; radiolabeling; radiochemistry; molecular imaging; radionuclide therapy

Dr. Ryuichi Nishii

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Guest Editor

Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), 4-9-1 Anagawa, Inage-ku, Chiba-shi, Chiba 263-8555, Japan
Interests: clinical nuclear medicine; diagnostic imaging; radionuclide therapy; molecular imaging; radiation dosimetry; translational imaging research

Special Issue Information

Dear Colleagues,

In recent years, theranostics (a word coined from “therapeutics” and “diagnostics”) have attracted much attention in oncology. A typical theranostic system has an imaging component for investigating a lesion site before treatment and a corresponding therapeutic one. Because the diagnosis makes the selection of suitable treatment and dose adjustment for each patient possible, theranostics can contribute to the realization of personalized medicine. Theranostics combined with a diagnostic and a therapeutic radionuclide is called “radiotheranostics.” This Special Issue will focus on the synthesis and/or evaluation of radiolabeled compounds containing dosimetry for their clinical application, radionuclide production and separation, and combination of a radionuclide with other modalities for not only radiotheranostics but also imaging as companion diagnosis.

You are cordially invited to contribute to this Special Issue “Recent Advances in Techniques with Radionuclide for Theranostic Drugs” with original articles, as well as reviews and short communications. Areas of interest include, but are not limited to the following Keywords.

Dr. Kazuma Ogawa
Dr. Shigeki Watanabe
Dr. Ryuichi Nishii
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. 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

Synthesis and evaluation of radiolabeled compounds for radiotheranostics
Synthesis and evaluation of radiolabeled compounds for imaging as companion diagnosis
Techniques using radiolabeled compounds for drug development
Production and separation of radionuclides for nuclear medicine
Combination of radionuclides (radiolabeled compounds) with other modalities
Pharmacokinetics, biodistributiion, and dosimetry for development of radiotheranostics

Published Papers (5 papers)

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Research

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11 pages, 827 KiB

Open AccessArticle

Positron Emission Intensity in the Decay of ^86gY for Use in Dosimetry Studies

by M. Shuza Uddin, Syed M. Qaim, Bernhard Scholten, M. Shamsuzzoha Basunia, Lee A. Bernstein, Ingo Spahn and Bernd Neumaier

Molecules 2022, 27(3), 768; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030768 - 25 Jan 2022

Cited by 4 | Viewed by 1996

Abstract

The β⁺-emitting radionuclide ^86gY (t_1/2 = 14.7 h) forms a matched-pair with the β⁻-emitting therapeutic radionuclide ⁹⁰Y (t_1/2 = 2.7 d) for theranostic application in medicine. This approach demands a precise knowledge of the positron emission probability of the PET nuclide which was until recently rather uncertain for ^86gY. In this work, an ^86gY source of high radionuclidic purity was prepared and a direct measurement of the positron emission intensity per 100 decay of the parent (hereafter “positron emission intensity”) was performed using high-resolution HPGe detector γ-ray spectroscopy. The electron capture intensity was also determined as an additional check by measuring the K_α and K_β X-rays of energies 14.1 and 15.8 keV, respectively, using a low energy HPGe detector. From those measurements, normalized values of 27.2 ± 2.0% for β⁺-emission and 72.8 ± 2.0% for EC were obtained. These results are in excellent agreement with values recently reported in the literature based on a detailed decay scheme study. Full article

(This article belongs to the Special Issue Recent Advances in Techniques with Radionuclide for Theranostic Drugs)

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14 pages, 1976 KiB

Open AccessArticle

Re-Evaluations of Zr-DFO Complex Coordination Chemistry for the Estimation of Radiochemical Yields and Chelator-to-Antibody Ratios of ⁸⁹Zr Immune-PET Tracers

by Ryota Imura, Hiroyuki Ida, Ichiro Sasaki, Noriko S. Ishioka and Shigeki Watanabe

Molecules 2021, 26(16), 4977; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26164977 - 17 Aug 2021

Cited by 8 | Viewed by 3464

Abstract

(1) Background: Deferoxamine B (DFO) is the most widely used chelator for labeling of zirconium-89 (⁸⁹Zr) to monoclonal antibody (mAb). Despite the remarkable developments of the clinical ⁸⁹Zr-immuno-PET, chemical species and stability constants of the Zr-DFO complexes remain controversial. The aim of this study was to re-evaluate their stability constants by identifying species of Zr-DFO complexes and demonstrate that the stability constants can estimate radiochemical yield (RCY) and chelator-to-antibody ratio (CAR). (2) Methods: Zr-DFO species were determined by UV and ESI-MS spectroscopy. Stability constants and speciation of the Zr-DFO complex were redetermined by potentiometric titration. Complexation inhibition of Zr-DFO by residual impurities was investigated by competition titration. (3) Results: Unknown species, ZrH_qDFO₂, were successfully detected by nano-ESI-Q-MS analysis. We revealed that a dominant specie under radiolabeling condition (pH 7) was ZrHDFO, and its stability constant (logβ₁₁₁) was 49.1 ± 0.3. Competition titration revealed that residual oxalate inhibits Zr-DFO complex formation. RCYs in different oxalate concentration (0.1 and 0.04 mol/L) were estimated to be 86% and >99%, which was in good agreement with reported results (87%, 97%). (4) Conclusion: This study succeeded in obtaining accurate stability constants of Zr-DFO complexes and estimating RCY and CAR from accurate stability constants established in this study. Full article

(This article belongs to the Special Issue Recent Advances in Techniques with Radionuclide for Theranostic Drugs)

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13 pages, 877 KiB

Open AccessFeature PaperArticle

Development of Radiogallium-Labeled Peptides for Platelet-Derived Growth Factor Receptor β (PDGFRβ) Imaging: Influence of Different Linkers

by Nurmaya Effendi, Kenji Mishiro, Kazuhiro Shiba, Seigo Kinuya and Kazuma Ogawa

Molecules 2021, 26(1), 41; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26010041 - 23 Dec 2020

Cited by 13 | Viewed by 2343

Abstract

The purpose of this study is to develop peptide-based platelet-derived growth factor receptor β (PDGFRβ) imaging probes and examine the effects of several linkers, namely un-natural amino acids (D-alanine and β-alanine) and ethylene-glycol (EG), on the properties of Ga-DOTA-(linker)-IPLPPPRRPFFK peptides. Seven radiotracers, ⁶⁷Ga-DOTA-(linker)-IPLPPPRRPFFK peptides, were designed, synthesized, and evaluated. The stability and cell uptake in PDGFRβ positive peptide cells were evaluated in vitro. The biodistribution of [⁶⁷Ga]Ga-DOTA-EG₂-IPLPPPRRPFFK ([⁶⁷Ga]27) and [⁶⁷Ga]Ga-DOTA-EG₄-IPLPPPRRPFFK ([⁶⁷Ga]28), which were selected based on in vitro stability in murine plasma and cell uptake rates, were determined in BxPC3-luc-bearing nu/nu mice. Seven ⁶⁷Ga-labeled peptides were successfully synthesized with high radiochemical yields (>85%) and purities (>99%). All evaluated radiotracers were stable in PBS (pH 7.4) at 37 °C. However, only [⁶⁷Ga]27 and [⁶⁷Ga]28 remained more than 75% after incubation in murine plasma at 37 °C for 1 h. [⁶⁷Ga]27 exhibited the highest BxPC3-luc cell uptake among the prepared radiolabeled peptides. As regards the results of the biodistribution experiments, the tumor-to-blood ratios of [⁶⁷Ga]27 and [⁶⁷Ga]28 at 1 h post-injection were 2.61 ± 0.75 and 2.05 ± 0.77, respectively. Co-injection of [⁶⁷Ga]27 and an excess amount of IPLPPPRRPFFK peptide as a blocking agent can significantly decrease this ratio. However, tumor accumulation was not considered sufficient. Therefore, further probe modification is required to assess tumor accumulation for in vivo imaging. Full article

(This article belongs to the Special Issue Recent Advances in Techniques with Radionuclide for Theranostic Drugs)

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14 pages, 2391 KiB

Open AccessArticle

PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response

by Aladdin Riad, Sarah B. Gitto, Hwan Lee, Harrison D. Winters, Paul M. Martorano, Chia-Ju Hsieh, Kuiying Xu, Dalia K. Omran, Daniel J. Powell, Jr., Robert H. Mach and Mehran Makvandi

Molecules 2020, 25(24), 6029; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25246029 - 19 Dec 2020

Cited by 20 | Viewed by 3611

Abstract

Theranostics are emerging as a pillar of cancer therapy that enable the use of single molecule constructs for diagnostic and therapeutic application. As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 can be safely targeted with Auger emitters to induce DNA damage in tumors. Here, we investigated a radioiodinated PARP inhibitor, [¹²⁵I]KX1, and show drug target specific DNA damage and subsequent killing of BRCA1 and non-BRCA mutant ovarian cancer cells at sub-pharmacological concentrations several orders of magnitude lower than traditional PARP inhibitors. Furthermore, we demonstrated that viable tumor tissue from ovarian cancer patients can be used to screen tumor radiosensitivity ex-vivo, enabling the direct assessment of therapeutic efficacy. Finally, we showed tumors can be imaged by single-photon computed tomography (SPECT) with PARP theranostic, [¹²³I]KX1, in a human ovarian cancer xenograft mouse model. These data support the utility of PARP-1 targeted radiopharmaceutical therapy as a theranostic option for PARP-1 overexpressing ovarian cancers. Full article

(This article belongs to the Special Issue Recent Advances in Techniques with Radionuclide for Theranostic Drugs)

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Review

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11 pages, 2013 KiB

Open AccessReview

Clinical Perspectives of Theranostics

by Shozo Okamoto, Tohru Shiga and Nagara Tamaki

Molecules 2021, 26(8), 2232; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26082232 - 13 Apr 2021

Cited by 19 | Viewed by 3327

Abstract

Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine. Full article

(This article belongs to the Special Issue Recent Advances in Techniques with Radionuclide for Theranostic Drugs)

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