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Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design
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Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 8308

Special Issue Editors

Dr. Carlo Aprile

E-Mail Website
Guest Editor
IRCCS Fondazione Policlinico San Matteo, Nuclear Medicine Unit, I-27100 Pavia, Italy
Interests: radiopharmacology; oncology imaging; amyloidosis
Special Issues, Collections and Topics in MDPI journals
Dr. Onelio Geatti

E-Mail Website
Guest Editor
Studio di Radiologia Bazzocchi, 34135 Trieste, Italy
Interests: thyroid; PET imaging; oncology diagnosis and therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Lorenzo Lodola

E-Mail Website
Guest Editor
IRCCS Fondazione Policlinico San Matteo, Nuclear Medicine Unit, I-27100 Pavia, Italy
Interests: radiopharmaceuticals; radioactive tracers; nuclear medicine radiolabeling; new PET imaging radionuclides
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Targeted radionuclide therapy (TRT) can be defined by the delivery of radionuclides to a tumor-associated target, which may be present in the tumor cell itself or in the microenvironment. Apart from some exceptions, as in the case of 131I in differentiated thyroid cancer, radiation is delivered by a vector which recognizes a receptor or an antigen or is an element of a metabolic pathway.

The design of a radiopharmaceutical for TRT requires a multidisciplinary team involving biologist, radio chemist, radio pharmacologist, medical, and physical staff.  After conjugation, usually by means of a bifunctional chelator, the compound may lose some affinity for the target. Great efforts have been made to select the more specific ligand and optimal labelling method in order to increase the specificity for the tumor tissue and the residence time to decrease the dose to normal tissues and critical organ subregions.

Molecular biology plays a fundamental role also in the field of nanosized particles loaded with radionuclides; specific coating may drive these particles towards the tumor, reducing the RES uptake.

Contributing papers to this Special Issue will present recent progress in the molecular approach to TRT of cancer, with emphasis on how to better design a radiopharmaceutical.

Dr. Carlo Aprile
Dr. Onelio Geatti
Dr. Lorenzo Lodola
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. Current Issues in Molecular Biology 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 2200 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 mechanisms
  • radiopharmaceutical
  • radionuclide therapy
  • alpha emitters
  • beta emitters
  • radiobiology
  • nuclear medicine

Published Papers (5 papers)

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Editorial

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4 pages, 188 KiB  
Editorial
Editorial for the Special Issue “Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design”
by Carlo Aprile, Onelio Geatti, Letizia Canziani and Lorenzo Lodola
Curr. Issues Mol. Biol. 2024, 46(3), 2398-2401; https://doi.org/10.3390/cimb46030152 - 13 Mar 2024
Viewed by 583
Abstract
Targeted radionuclide therapy (TRT) is gaining wide and rapid acceptance in clinical practice as it can deliver alpha or beta irradiation to a tumor-associated target which may be present in the tumor cell itself or in the microenvironment [...] Full article
(This article belongs to the Special Issue Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design)

Research

Jump to: Editorial, Review

24 pages, 2395 KiB  
Article
Transcriptomes of Wet Skin Biopsies Predict Outcomes after Ionizing Radiation Exposure with Potential Dosimetric Applications in a Mouse Model
by Abdulnaser Alkhalil, John Clifford, Stacyann M. Miller, Aarti Gautam, Marti Jett, Rasha Hammamieh, Lauren T. Moffatt and Jeffrey W. Shupp
Curr. Issues Mol. Biol. 2022, 44(8), 3711-3734; https://doi.org/10.3390/cimb44080254 - 18 Aug 2022
Viewed by 1462
Abstract
Countermeasures for radiation diagnosis, prognosis, and treatment are trailing behind the proliferation of nuclear energy and weaponry. Radiation injury mechanisms at the systems biology level are not fully understood. Here, mice skin biopsies at h2, d4, d7, d21, and d28 after exposure to [...] Read more.
Countermeasures for radiation diagnosis, prognosis, and treatment are trailing behind the proliferation of nuclear energy and weaponry. Radiation injury mechanisms at the systems biology level are not fully understood. Here, mice skin biopsies at h2, d4, d7, d21, and d28 after exposure to 1, 3, 6, or 20 Gy whole-body ionizing radiation were evaluated for the potential application of transcriptional alterations in radiation diagnosis and prognosis. Exposure to 20 Gy was lethal by d7, while mice who received 1, 3, or 6 Gy survived the 28-day time course. A Sammon plot separated samples based on survival and time points (TPs) within lethal (20 Gy) and sublethal doses. The differences in the numbers, regulation mode, and fold change of significantly differentially transcribed genes (SDTGs, p < 0.05 and FC > 2) were identified between lethal and sublethal doses, and down and upregulation dominated transcriptomes during the first post-exposure week, respectively. The numbers of SDTGs and the percentages of upregulated ones revealed stationary downregulation post-lethal dose in contrast to responses to sublethal doses which were dynamic and largely upregulated. Longitudinal up/downregulated SDTGs ratios suggested delayed and extended responses with increasing IR doses in the sublethal range and lethal-like responses in late TPs. This was supported by the distributions of common and unique genes across TPs within each dose. Several genes with potential dosimetric marker applications were identified. Immune, fibrosis, detoxification, hematological, neurological, gastric, cell survival, migration, and proliferation radiation response pathways were identified, with the majority predicted to be activated after sublethal and inactivated after lethal exposures, particularly during the first post-exposure week. Full article
(This article belongs to the Special Issue Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design)
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9 pages, 1233 KiB  
Article
Propensity Score-Matched Analysis to Identify Pathways Associated with Loss of Sodium Iodide Symporter in Papillary Thyroid Cancer
by Fang Lee, Chi-Yu Kuo, Chung-Hsin Tsai and Shih-Ping Cheng
Curr. Issues Mol. Biol. 2022, 44(4), 1488-1496; https://doi.org/10.3390/cimb44040101 - 26 Mar 2022
Cited by 2 | Viewed by 1852
Abstract
Sodium iodide symporter (NIS) expression in thyroid follicular cells plays an important role in normal physiology and radioactive iodine therapy for thyroid cancer. Loss of NIS expression is often seen in thyroid cancers and may lead to radioiodine refractoriness. To explore novel mechanisms [...] Read more.
Sodium iodide symporter (NIS) expression in thyroid follicular cells plays an important role in normal physiology and radioactive iodine therapy for thyroid cancer. Loss of NIS expression is often seen in thyroid cancers and may lead to radioiodine refractoriness. To explore novel mechanisms of NIS repression beyond oncogenic drivers, clinical and RNA-seq data from the thyroid cancer dataset of The Cancer Genome Atlas were analyzed. Propensity score matching was used to control for various genetic background factors. We found that tumoral NIS expression was negatively correlated with tumor size. Additionally, low NIS expression was the only factor associated with recurrence-free survival in a Cox multivariate regression analysis. After matching for clinicopathologic profiles and driver mutations, the principal component analysis revealed distinct gene expressions between the high and low NIS groups. Gene set enrichment analysis suggested the downregulation of hedgehog signaling, immune networks, and cell adhesions. Positively enriched pathways included DNA replication, nucleotide excision repair, MYC, and Wnt/β-catenin pathways. In summary, we identified several potential targets which could be exploited to rescue the loss of NIS expression and develop redifferentiation strategies to facilitate radioactive iodine therapy for thyroid cancer. Full article
(This article belongs to the Special Issue Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design)
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Review

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15 pages, 613 KiB  
Review
Head-to-Head Comparison between Peptide-Based Radiopharmaceutical for PET and SPECT in the Evaluation of Neuroendocrine Tumors: A Systematic Review
by Giulia Poletto, Diego Cecchin, Stefania Sperti, Luca Filippi, Nicola Realdon and Laura Evangelista
Curr. Issues Mol. Biol. 2022, 44(11), 5516-5530; https://doi.org/10.3390/cimb44110373 - 07 Nov 2022
Cited by 8 | Viewed by 1521
Abstract
We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled [...] Read more.
We compared head-to-head the most used radiolabeled peptides for single photon computed emission tomography (SPECT) and positron emission tomography (PET) imaging of neuroendocrine tumors (NETs). A comprehensive literature search was performed in PubMed, Web of Science, and Scopus databases. The following words, coupled two by two, were used: 68Ga-DOTATOC; 68Ga-DOTATATE; 68Ga-DOTANOC; 99mTc-EDDA/HYNIC-TOC; 64Cu-DOTATATE; and 111In-DTPA-octreotide. Moreover, a second-step search strategy was adopted by using the following combined terms: “Somatostatin receptor imaging,”; “Somatostatin receptor imaging” and “Functional,”; “Somatostatin receptor imaging” and “SPECT,”; and “Somatostatin receptor imaging” and “PET”. Eligible criteria were: (1) original articles focusing on the clinical application of the radiopharmaceutical agents in NETs; (2) original articles in the English language; (3) comparative studies (head-to-head comparative or matched-paired studies). Editorials, letters to the editor, reviews, pictorial essays, clinical cases, or opinions were excluded. A total of 1077 articles were found in the three electronic databases. The full texts of 104 articles were assessed for eligibility. Nineteen articles were finally included. Most articles focused on the comparison between 111In-DTPA-Octreotide and 68Ga-DOTATOC/TATE. Few papers compared 64Cu-DOTATATE and 68Ga-DOTATOC/TATE, or SPECT tracers. The rates of true positivity were 63.7%, 58.5%, 78.4% and 82.4%, respectively, for 111In-DTPA-Octreotide, 99mTc-EDDA/HYNIC-TOC, 68Ga-DOTATATE/TOC and 64Cu-DOTATATE. In conclusion, as highly expected, PET tracers are more suitable for the in vivo identification of NETs. Indeed, in comparative studies, they demonstrated a higher true positive rate than SPECT agents. Full article
(This article belongs to the Special Issue Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design)
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16 pages, 1502 KiB  
Review
Radionuclide Delivery Strategies in Tumor Treatment: A Systematic Review
by Giulia Poletto, Diego Cecchin, Paola Bartoletti, Francesca Venturini, Nicola Realdon and Laura Evangelista
Curr. Issues Mol. Biol. 2022, 44(8), 3267-3282; https://doi.org/10.3390/cimb44080225 - 22 Jul 2022
Cited by 3 | Viewed by 2000
Abstract
The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms “radionuclides”, “liposomes”, “avidin–biotin interaction”, “theranostic”, and “molecular [...] Read more.
The aim of this review was to assess recent progress in targeted radionuclide tumor therapy, focusing on the best delivery strategies. A literature search was conducted in PubMed, Web of Science, and Scopus using the terms “radionuclides”, “liposomes”, “avidin–biotin interaction”, “theranostic”, and “molecular docking”. The 10 year filter was applied, except for the avidin–biotin interaction. Data were retrieved from both preclinical and clinical settings. Three targeting strategies were considered: pretargeting, liposomes, and ligands. Pretargeting can be achieved by exploiting the avidin–biotin interaction. This strategy seems very promising, although it has been investigated mainly in resectable tumors. Radiolabeled liposomes have attracted new interest as probes to identify the most suitable patients for treatment with liposomal formulations of common chemotherapeutics. The use of ligands for the delivery of radiotherapeutics to a specific target is still the most appealing strategy for treating tumors. The most appropriate ligand can be identified by virtually simulating its interaction with the receptor. All strategies showed great potential for use in targeted radionuclide therapy, but they also have numerous drawbacks. The most promising option is probably the one based on the use of new ligands. Full article
(This article belongs to the Special Issue Molecular Biology in Targeted Radionuclide Therapy Radiopharmaceutical Design)
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