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Selected Papers from 12th International Symposium on Targeted Alpha Therapy
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Selected Papers from 12th International Symposium on Targeted Alpha Therapy

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

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 5845

Special Issue Editor

Dr. Kalevi Kairemo

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Guest Editor
1. Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2. Department of Theragnostics, Docrates Cancer Center, 00180 Helsinki, Finland
Interests: nanoparticles; peptides; monoclonal antibodies; radiochemistry; pharmaceutical medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will be a collection of the best presentations from the 12th International Symposium on Targeted Alpha Therapy (TAT 12) conference held in Cape Town, South Africa from the 27th of February to the 2nd of March 2023. This 12th conference continued a successful series of international symposia on this topic initiated by the Joint Research Centre of the European Commission in 1997 with  previous meetings in Karlsruhe (1997, 2000), Heidelberg (2002), Düsseldorf (2004), Aachen (2007), Toronto (2009), Berlin (2011), Oak Ridge (2013), Warsaw (2015), Kanazawa (2017) and Ottawa (2019).

The conference issue will provide information on the newest developments in preclinical studies, dosimetry and instrumentation, quality assurance, regulatory, targeting, radiochemistry, and nuclide production and supply of alpha-emitting radionuclides. This IJMS special issue will have a special emphasis on biochemistry, molecular and cell biology, molecular biophysics, molecular medicine in targeted alpha therapy applications. Since IJMS is a journal of molecular science, thus pure clinical studies will not suitable for our journal.

The special topics include:

  • Pre-clinical Studies and Experiences
  • Radiouclide Production/ Supply
  • Radiochemistry
  • Targeting and Delivery Systems, such as new chelation mechansims, nanocarriers, encapsulation approaches
  • Quality and Regulatory Aspects (e.g. dealing with waste, FDA approvals etc.)
  • Related Topics

Dr. Kalevi Kairemo
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

  • precision oncology
  • oncology
  • radionuclide therapy
  • targeted therapy
  • targeted alpha therapy
  • Lead radioisotopes
  • Bismuth radioisotopes
  • Radium radioisotopes
  • Actinium radioisotopes
  • Thorium radioistotopes
  • PSMA
  • prostate cancer
  • endocrine
  • neuroendocrine neoplasms
  • somatostatin analogs
  • Monte Carlo
  • computational methods
  • daughter radionuclides
  • dosimetry
  • small-scale/microdosimetry
  • targeted alpha therapy
  • radiobiology
  • target chemistry

Published Papers (3 papers)

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Research

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13 pages, 2143 KiB  
Article
Comparative Analysis of Morphological and Functional Effects of 225Ac- and 177Lu-PSMA Radioligand Therapies (RLTs) on Salivary Glands
by Benedikt Feuerecker, Andrei Gafita, Thomas Langbein, Robert Tauber, Christof Seidl, Frank Bruchertseifer, Jürgen E. Gschwendt, Wolfgang A. Weber, Calogero D’Alessandria, Alfred Morgenstern and Matthias Eiber
Int. J. Mol. Sci. 2023, 24(23), 16845; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242316845 - 28 Nov 2023
Viewed by 1019
Abstract
Most Prostate Specific Membrane Antigens (PSMAs) targeting small molecules accumulate in the salivary glands (SGs), raising concerns about SG toxicity, especially after repeated therapies or therapy with 225Ac-labeled ligands. SG toxicity is assessed clinically by the severity of patient-reported xerostomia, but this [...] Read more.
Most Prostate Specific Membrane Antigens (PSMAs) targeting small molecules accumulate in the salivary glands (SGs), raising concerns about SG toxicity, especially after repeated therapies or therapy with 225Ac-labeled ligands. SG toxicity is assessed clinically by the severity of patient-reported xerostomia, but this parameter can be challenging to objectively quantify. Therefore, we explored the feasibility of using SG volume as a biomarker for toxicity. In 21 patients with late-stage metastatic resistant prostate cancer (mCRPC), the PSMA volume and ligand uptake of SG were analyzed retrospectively before and after two cycles of 177Lu-PSMA (LuPSMA; cohort A) and before and after one cycle of 225Ac-PSMA-617 (AcPSMA, cohort B). Mean Volume-SG in cohort A was 59 ± 13 vs. 54 ± 16 mL (−10%, p = 0.4), and in cohort B, it was 50 ± 13 vs. 40 ± 11 mL (−20%, p = 0.007), respectively. A statistically significant decrease in the activity concentration in the SG was only observed in group B (SUVmean: 9.2 ± 2.8 vs. 5.3 ± 1.8, p < 0.0001; vs. A: SUVmean: 11.2 ± 3.3 vs. 11.1 ± 3.5, p = 0.8). SG volume and PSMA-ligand uptake are promising markers to monitor the SG toxicity after a PSMA RLT. Full article
(This article belongs to the Special Issue Selected Papers from 12th International Symposium on Targeted Alpha Therapy)
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12 pages, 2294 KiB  
Article
Long-Term Tumor Control Following Targeted Alpha Therapy (TAT) of Low-Grade Gliomas (LGGs): A New Treatment Paradigm?
by Leszek Krolicki, Jolanta Kunikowska, Dominik Cordier, Nedelina Slavova, Henryk Koziara, Frank Bruchertseifer, Helmut R. Maecke, Alfred Morgenstern and Adrian Merlo
Int. J. Mol. Sci. 2023, 24(21), 15701; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242115701 - 28 Oct 2023
Viewed by 1054
Abstract
The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [213Bi]Bi/[225 [...] Read more.
The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [213Bi]Bi/[225Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [90Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule–catheter system. The activity used for radiolabeling was 2–2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG. Full article
(This article belongs to the Special Issue Selected Papers from 12th International Symposium on Targeted Alpha Therapy)
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Review

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15 pages, 290 KiB  
Review
Targeted Alpha-Particle Therapy: A Review of Current Trials
by Albert Jang, Ayse T. Kendi, Geoffrey B. Johnson, Thorvardur R. Halfdanarson and Oliver Sartor
Int. J. Mol. Sci. 2023, 24(14), 11626; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411626 - 19 Jul 2023
Cited by 11 | Viewed by 3144
Abstract
Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently [...] Read more.
Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic. Full article
(This article belongs to the Special Issue Selected Papers from 12th International Symposium on Targeted Alpha Therapy)
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