Special Issue "The Future Direction of Radiopharmaceutical Development for Cancer Theranostics"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editor

Dr. Martina Benešová
E-Mail Website
Guest Editor
Research Group Molecular Biology of Systemic Radiotherapy, Research Program Imaging and Radiooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 223, D-69120 Heidelberg, Germany.
Interests: radiopharmaceutical chemistry; coordination chemistry; theranostic radiopharmaceuticals; molecular biology of systemic therapy; radiobiology

Special Issue Information

Dear Colleagues,

The journal Pharmaceuticals is planning to publish a Special Issue covering the topic “The Future Direction of Radiopharmaceutical Development for Cancer Theranostics”, and I am cordially inviting you to contribute an article to this volume.

With rapid population growth and aging, cancer is expected to rank as the leading cause of death in every country of the world in the 21st century. The development of improved diagnostic and therapeutic strategies for the management of cancer is, therefore, of utmost importance. The term “theranostics” is used for combined diagnosis and therapy, among others, in the field of radiooncology. The application of the same vector molecule with either a diagnostic or therapeutic radionuclide has the potential to overcome undesirable differences in selectivity and biodistribution that usually exist for distinct agents.

In recent years, the field of cancer radiotheranostics has evolved considerably due to the definition of suitable biological targets and targeting strategies (e.g., SSTR- and PSMA-based concepts), development of various pharmaceuticals (e.g., small low- and high-molecular-weight molecules, various antibody-like structures and nanoparticles), and increased availability of prospective diagnostic and therapeutic radionuclides (e.g., α-, β+-, β-, and Auger electron-emitters), as well as improvement of imaging techniques. In addition to optimal treatment choice, an improved staging of primary and recurrent disease, prognostic stratification, therapy follow-up, and guidance of clinical trial enrollment may maximize the likelihood of successful theranostic outcomes.

Targeted radionuclide therapy (TRNT) is an attractive treatment option in the field of cancer radiotheranostics, focusing on particular biological targets and their environments. Currently, targeted alpha therapy (TAT) represents the most rapidly developing field in nuclear medicine. Despite its great potential for cancer treatment, translation of TAT into the clinical setting is rather slow, mainly due to the lack of pre-clinical research directly linked to limited radionuclide availability. For many years, large-field radiation has been used for its immunosuppressive ability. On the contrary, the application of radioimmunotherapy demonstrates a more complex relationship with the immune system while inducing substantial changes in the tumor microenvironment beyond cellular cytotoxicity. Based on the critical role of the immune system in cancer development and dissemination, TRNT may potentially be combined with various strategies triggering immune response in order to achieve enhanced anti-tumor effect.

The purpose of this Special Issue is to host research and review papers on the development of novel radiopharmaceuticals and therapy strategies for cancer theranostics, which hold a great promise for improved patients’ outcomes in the future. Areas of interest include, but are not limited to: 

  • Identification of new targets for cancer theranostics;
  • Design of novel radiopharmaceuticals for cancer theranostics;
  • Evaluation of non-standard radionuclides potentially suitable for cancer theranostics;
  • Experimental targeted radionuclide therapy strategies;
  • Prospective combination therapy with targeted radionuclide therapy involved.

Dr. Martina Benešová
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 papers will be 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 quarterly 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 1000 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

  • novel cancer targets
  • non-standard radionuclides
  • molecular imaging
  • targeted radionuclide therapy
  • theranostic radiopharmaceuticals
  • radioimmunotherapy
  • nuclear medicine
  • personalized medicine
  • precision medicine

Published Papers (2 papers)

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Research

Open AccessArticle
Synergistic Effect of a HER2 Targeted Thorium-227 Conjugate in Combination with Olaparib in a BRCA2 Deficient Xenograft Model
Pharmaceuticals 2019, 12(4), 155; https://doi.org/10.3390/ph12040155 - 15 Oct 2019
Abstract
Targeted thorium-227 conjugates (TTCs) represent a novel class of therapeutic radiopharmaceuticals for the treatment of cancer. TTCs consist of the alpha particle emitter thorium-227 complexed to a 3,2-hydroxypyridinone chelator conjugated to a tumor-targeting monoclonal antibody. The high energy and short range of the [...] Read more.
Targeted thorium-227 conjugates (TTCs) represent a novel class of therapeutic radiopharmaceuticals for the treatment of cancer. TTCs consist of the alpha particle emitter thorium-227 complexed to a 3,2-hydroxypyridinone chelator conjugated to a tumor-targeting monoclonal antibody. The high energy and short range of the alpha particles induce potent and selective anti-tumor activity driven by the induction of DNA damage in the target cell. Methods: The efficacy of human epidermal growth factor receptor 2 (HER2)-TTC was tested in combination in vitro and in vivo with the poly ADP ribose polymerase (PARP) inhibitor (PARPi), olaparib, in the human colorectal adenocarcinoma isogenic cell line pair DLD-1 and the knockout variant DLD-1 BRCA2 -/- Results: The in vitro combination effects were determined to be synergistic in DLD-1 BRCA2 -/- and additive in DLD-1 parental cell lines. Similarly, the in vivo efficacy of the combination was determined to be synergistic only in the DLD-1 BRCA2 -/- xenograft model, with statistically significant tumor growth inhibition at a single TTC dose of 120 kBq/kg body weight (bw) and 50 mg/kg bw olaparib (daily, i.p. for 4 weeks), demonstrating comparable tumor growth inhibition to a single TTC dose of 600 kBq/kg bw. Conclusions: This study supports the further investigation of DNA damage response inhibitors in combination with TTCs as a new strategy for the effective treatment of mutation-associated cancers. Full article
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Open AccessArticle
Radioimmunotherapy in Non-Hodgkin’s Lymphoma: Retrospective Adverse Event Profiling of Zevalin and Bexxar
Pharmaceuticals 2019, 12(4), 141; https://doi.org/10.3390/ph12040141 - 20 Sep 2019
Abstract
The development of monoclonal antibodies has dramatically changed the outcome of patients with non-Hodgkin’s lymphoma (NHL), the most common hematological malignancy. However, despite the satisfying results of monoclonal antibody treatment, only few NHL patients are permanently cured with single-agent therapies. In this context, [...] Read more.
The development of monoclonal antibodies has dramatically changed the outcome of patients with non-Hodgkin’s lymphoma (NHL), the most common hematological malignancy. However, despite the satisfying results of monoclonal antibody treatment, only few NHL patients are permanently cured with single-agent therapies. In this context, radioimmunotherapy, the administration of radionuclides conjugated to monoclonal antibodies, is aimed to augment the single-agent efficacy of immunotherapy in order to deliver targeted radiation to tumors, particularly CD20+ B-cell lymphomas. Based on evidence from several trials in NHL, the radiolabeled antibodies 90Y-ibritumomab tiuxetan (Zevalin, Spectrum Pharmaceuticals) and 131I-tositumomab (Bexxar, GlaxoSmithKline) received FDA approval in 2002 and 2003, respectively. However, none of the two radioimmunotherapeutic agents has been broadly applied in clinical practice. The main reason for the under-utilization of radioimmunotherapy includes economic and logistic considerations. However, concerns about potential side effects have also been raised. Driven by these developments, we performed retrospective analysis of adverse events reporting Zevalin or Bexxar, extracted from the FDA’s Adverse Event Reporting System (FAERS) and the World Health Organization’s VigiBase repository. Our results indicate that the two radioimmunotherapeutic agents have both related and distinct side effect profiles and confirm their known toxicological considerations. Our work also suggests that computational analysis of real-world post-marketing data can provide informative clinical insights. While more prospective studies are necessary to fully characterize the efficacy and safety of radioimmunotherapy, we expect that it has not yet reached its full therapeutic potential in modern hematological oncology. Full article
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