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Studies include astatine-211 precursor development and mechanistic comparisons of TRT versus external beam radiation, plus radiosensitization strategies and PARP-1–targeted approaches in prostate cancer 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developing reliable chemistry for complex radionuclides.",{"name":70,"@type":61,"acceptedAnswer":71},"How do radiobiological outcomes differ between TRT and external beam radiation?",{"text":72,"@type":64},"A referenced in vitro study reports similar cell-killing mechanisms for 177Lu-DOTATATE and EBRT, but different extent and kinetics of killing, DNA damage differences, and stronger olaparib radiosensitization with EBRT than with TRT.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},383647,1790831644,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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Infections  \nBart C. H. van der Wal 1 and Ekaterina Dadachova 2, *  \nCitation: van der Wal, B.C.H.; Dadachova, E. Targeted Radionuclide Therapy of Cancer and Infections. Int.  \nJ. Mol. Sci. 2023, 24, 9081. [https://](https://)[ ](https://)[doi.org/10.3390/ijms24109081](doi.org/10.3390/ijms24109081)  \nReceived: 30 April 2023  \nAccepted: 18 May 2023  \nPublished: 22 May 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands; [b.c.h.vanderwal@umcutrecht.nl](b.c.h.vanderwal@umcutrecht.nl)  \n2 College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada  \n* Correspondence: [ekaterina.dadachova@usask.ca](ekaterina.dadachova@usask.ca)  \nTargeted radionuclide therapy (TRT) has been burgeoning worldwide, with several radiopharmaceuticals for the treatment of metastatic cancers being approved for clinical use. There are many promising novel radiopharmaceuticals currently in preclinical development, and several are already being evaluated in Phase 0 or Phase 1 clinical trials. Many research groups are performing groundbreaking radiobiological and mechanistic studies in order to elucidate the mechanisms underpinning the efficacy of TRT, with the goal of making this modality more effective and safe. In addition, the recent COVID-19 pandemic has demonstrated the need for “out of the box” thinking when it comes to novel therapeutics for combating emerging infectious diseases. In this regard, applying the principles of TRT to the treatment of a whole plethora of infectious diseases seems to be an attractive pproach.  \nThis Special Issue,“Targeted Radionuclide Therapy of Cancer and Infections”, in the International Journal of Molecular Sciences includes six contributions—four original articles and two reviews—covering a very broad range of topics, from making radioastatinated precursors to the radiobiological mechanisms ofTRT to evaluating radiopharmaceuticals for cancer and infection in animal models to clinical trials and approved radiopharmaceuticals for cancer therapy.  \nIn the area of radiopharmaceutical chemistry, Li et al. [1] examined an alternative approach of making precursors for the labeling of molecules with astatine-211 (211At), as this alpha emitter has a lot of promise for TRT. Specifically, the authors tested the hypothesis that a specific type of astatinated aryl compound with highly oxidized At atoms could exhibit stability in vivo towards deastatination. To accomplish this, para-stannylbenzoic acid derivatives were synthesized and radiolabeled with 125I and 211At, followed by the oxidization of the [125I]iodo and [211At]astato-benzamidyl-dPEG4-acid methyl ester derivatives for subsequent biodistribution in mice. While the oxidized radioiodinated derivative did not deiodinate in vivo, the oxidized [211At]astatinated benzamide derivative was shown to be unstable in vivo. These results highlight many challenges in developing reliable chemistry for making stable radiopharmaceuticals for TRT, especially the ones that incorporate radionuclides with very complex chemistry, such as At.  \nDetailed knowledge of radiobiological mechanisms of action of TRT agents is very important for developing novel radiopharmaceuticals, as well as for designing more effective and safe treatment regimens. Though TRT has been in development for several decades, many radiobiological mechanisms are still extrapolated from external beam radiation therapy (EBRT) in spite of stark differences in doses, dose rates, and times of administration between these two radiation tre","cbCaiilsXSjcs377","https://ap.wps.com/l/cbCaiilsXSjcs377","pdf",159701,"English","# Editorial overview\n## Applications of TRT in cancer and infections\n## Radiopharmaceutical chemistry for astatine-211\n## Radiobiological mechanisms: TRT versus external beam radiation\n## PARP-1 targeted TRT in prostate cancer models","[{\"question\":\"What is the focus of this editorial on targeted radionuclide therapy (TRT)?\",\"answer\":\"It reviews TRT’s growing clinical use for metastatic cancers and discusses opportunities to extend TRT principles to infectious diseases, emphasizing improved efficacy and safety through radiobiological understanding.\"},{\"question\":\"What chemistry challenge is discussed for astatine-211 radiopharmaceuticals?\",\"answer\":\"The editorial describes testing precursor stability for astatine-211 labeling, showing that an oxidized astatinated benzamide derivative was unstable in vivo, underscoring difficulty in developing reliable chemistry for complex radionuclides.\"},{\"question\":\"How do radiobiological outcomes differ between TRT and external beam radiation?\",\"answer\":\"A referenced in vitro study reports similar cell-killing mechanisms for 177Lu-DOTATATE and EBRT, but different extent and kinetics of killing, DNA damage differences, and stronger olaparib radiosensitization with EBRT than with TRT.\"}]","Targeted Radionuclide Therapy of Cancer and Infections | PDF",1790258555]