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  1. Article ; Online: A persistent belief in radiopharmaceutical therapy.

    Sgouros, George

    Medical physics

    2023  Volume 50 Suppl 1, Page(s) 104–108

    Abstract: Imaging and dosimetry physics are essential to the long-term success of radiopharmaceutical therapy (RPT), a cancer treatment modality that can deliver potent cytotoxic radiation to disseminated cancer cells. This is a review of my personal journey in ... ...

    Abstract Imaging and dosimetry physics are essential to the long-term success of radiopharmaceutical therapy (RPT), a cancer treatment modality that can deliver potent cytotoxic radiation to disseminated cancer cells. This is a review of my personal journey in this field.
    MeSH term(s) Humans ; Radiopharmaceuticals/therapeutic use ; Neoplasms/diagnostic imaging ; Neoplasms/radiotherapy ; Radiometry/methods ; Diagnostic Imaging
    Chemical Substances Radiopharmaceuticals
    Language English
    Publishing date 2023-02-17
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 188780-4
    ISSN 2473-4209 ; 0094-2405
    ISSN (online) 2473-4209
    ISSN 0094-2405
    DOI 10.1002/mp.16272
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  2. Article ; Online: Alpha and Beta Radiation for Theragnostics.

    Song, Hong / Sgouros, George

    PET clinics

    2024  

    Abstract: Targeted radionuclide therapy (TRT) has significantly evolved from its beginnings with iodine-131 to employing carrier molecules with beta emitting isotopes like lutetium-177. With the success of Lu-177-DOTATATE for neuroendocrine tumors and Lu-177-PSMA- ... ...

    Abstract Targeted radionuclide therapy (TRT) has significantly evolved from its beginnings with iodine-131 to employing carrier molecules with beta emitting isotopes like lutetium-177. With the success of Lu-177-DOTATATE for neuroendocrine tumors and Lu-177-PSMA-617 for prostate cancer, several other beta emitting radioisotopes, such as Cu-67 and Tb-161, are being explored for TRT. The field has also expanded into targeted alpha therapy (TAT) with agents like radium-223 for bone metastases in prostate cancer, and several other alpha emitter radioisotopes with carrier molecules, such as Ac-225, and Pb-212 under clinical trials. Despite these advancements, the scope of TRT in treating diverse solid tumors and integration with other therapies like immunotherapy remains under investigation. The success of antibody-drug conjugates further complements treatments with TRT, though challenges in treatment optimization continue.
    Language English
    Publishing date 2024-04-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2764575-7
    ISSN 1879-9809 ; 1556-8598
    ISSN (online) 1879-9809
    ISSN 1556-8598
    DOI 10.1016/j.cpet.2024.03.006
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  3. Article ; Online: Dosimetry, Radiobiology and Synthetic Lethality: Radiopharmaceutical Therapy (RPT) With Alpha-Particle-Emitters.

    Sgouros, George

    Seminars in nuclear medicine

    2020  Volume 50, Issue 2, Page(s) 124–132

    Abstract: As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha- ... ...

    Abstract As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.
    MeSH term(s) Alpha Particles/therapeutic use ; Humans ; Radiobiology ; Radiometry ; Radiopharmaceuticals/therapeutic use
    Chemical Substances Radiopharmaceuticals
    Language English
    Publishing date 2020-02-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 120248-0
    ISSN 1558-4623 ; 0001-2998
    ISSN (online) 1558-4623
    ISSN 0001-2998
    DOI 10.1053/j.semnuclmed.2019.11.002
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  4. Article ; Online: α-Particle-Emitter Radiopharmaceutical Therapy: Resistance Is Futile.

    Sgouros, George

    Cancer research

    2019  Volume 79, Issue 21, Page(s) 5479–5481

    Abstract: Alpha-emitter radiopharmaceutical therapy (α-RPT) is a treatment modality that is impervious to conventional cellular resistance mechanisms because of the unique properties of the α-particle. Radiobiological studies of α-particle emitters have been few ... ...

    Abstract Alpha-emitter radiopharmaceutical therapy (α-RPT) is a treatment modality that is impervious to conventional cellular resistance mechanisms because of the unique properties of the α-particle. Radiobiological studies of α-particle emitters have been few as they require detailed consideration of both biology and physics. Clinical studies of this radiation delivery modality have shown highly promising results in cancers that are resistant to other treatments. The work by Yard and colleagues published in this issue introduces an innovative approach to radiobiological investigations of α-RPT and highlights the specific physics considerations required to properly investigate this multidisciplinary treatment modality.
    MeSH term(s) Alpha Particles ; Humans ; Neoplasms ; Radiobiology ; Radiopharmaceuticals
    Chemical Substances Radiopharmaceuticals
    Language English
    Publishing date 2019-10-29
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-19-2806
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  5. Article ; Online: The Case for Dosimetry in Alpha-Emitter Therapy.

    Sgouros, George

    Journal of medical imaging and radiation sciences

    2019  Volume 50, Issue 4 Suppl 1, Page(s) S45–S46

    Abstract: Despite ongoing efforts with new chemotherapeutics, small-molecule inhibitors and biologics, patients with distant metastases continue to have a grim prognosis. Radiopharmaceutical therapy (RPT) with alpha-particle-emitting radionuclides has shown ... ...

    Abstract Despite ongoing efforts with new chemotherapeutics, small-molecule inhibitors and biologics, patients with distant metastases continue to have a grim prognosis. Radiopharmaceutical therapy (RPT) with alpha-particle-emitting radionuclides has shown efficacy against widespread disease. Alpha-particle emitters are particularly effective because their short range and high energy deposit density lead to complex and largely irreparable DNA double-strand breaks. The high potency against tumors can also lead to high toxicity. Unlike most systemic treatment of cancer, the biodistribution of RPT agents may be imaged in humans using nuclear medicine imaging modalities. In this context, dosimetry provides a precision medicine approach to implementing RPT with alpha-emitters.
    MeSH term(s) Alpha Particles/adverse effects ; Alpha Particles/therapeutic use ; Humans ; Neoplasms/radiotherapy ; Radiation Injuries/etiology ; Radiation Injuries/prevention & control ; Radiometry/methods ; Radiopharmaceuticals/adverse effects ; Radiopharmaceuticals/therapeutic use ; Radiotherapy/adverse effects ; Radiotherapy/methods ; Radiotherapy Dosage
    Chemical Substances Radiopharmaceuticals
    Language English
    Publishing date 2019-09-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2426513-5
    ISSN 1876-7982 ; 1939-8654
    ISSN (online) 1876-7982
    ISSN 1939-8654
    DOI 10.1016/j.jmir.2019.07.007
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    Zs.B 2541: Show issues Location:
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  6. Article ; Online: Radiopharmaceutical Therapy.

    Sgouros, George

    Health physics

    2018  Volume 116, Issue 2, Page(s) 175–178

    Abstract: Radiopharmaceutical therapy involves the use of radionuclides that are either conjugated to tumor-targeting agents (e.g., nanoscale constructs, antibodies, peptides, and small molecules) or that concentrate in tumors through natural physiological ... ...

    Abstract Radiopharmaceutical therapy involves the use of radionuclides that are either conjugated to tumor-targeting agents (e.g., nanoscale constructs, antibodies, peptides, and small molecules) or that concentrate in tumors through natural physiological mechanisms that occur predominantly in neoplastic cells. In the latter category, radioiodine therapy of thyroid cancer is the prototypical and most widely implemented radiopharmaceutical therapy. In the category of radionuclide-ligand conjugates, antibody and peptide conjugates have been studied extensively. The efficacy of radiopharmaceutical therapy relies on the ability to deliver cytotoxic radiation to tumor cells without causing prohibitive normal tissue toxicity. After some 30 y of preclinical and clinical research, a number of recent developments suggest that radiopharmaceutical therapy is poised to emerge as an important and widely recognized therapeutic modality. These developments include the substantial investment in antibodies by the pharmaceutical industry and the compelling rationale to build upon this already existing and widely tested platform. In addition, the growing recognition that the signaling pathways responsible for tumor cell survival and proliferation are less easily and durably inhibited than originally envisioned has also provided a rationale for identifying agents that are cytotoxic rather than inhibitory. A number of radiopharmaceutical agents are currently undergoing clinical trial investigation; these include beta-particle emitters, such as Lu, that are being used to label antisomatostatin receptor peptides for neuroendocrine cancers and also prostate-specific membrane antigen targeting small molecules for prostate cancer. Alpha-particle-emitting radionuclides have also been studied for radiopharmaceutical therapy; these include At for glioblastoma, Ac for leukemias and prostate cancer, Pb for breast cancer, and Ra for prostate cancer. The alpha emitters have tended to show particular promise, and there is substantial interest in further developing these agents for therapy of cancers that are particularly difficult to treat.
    MeSH term(s) Humans ; Neoplasms/diagnostic imaging ; Neoplasms/radiotherapy ; Radiation Dosage ; Radiopharmaceuticals/therapeutic use
    Chemical Substances Radiopharmaceuticals
    Language English
    Publishing date 2018-12-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2406-5
    ISSN 1538-5159 ; 0017-9078
    ISSN (online) 1538-5159
    ISSN 0017-9078
    DOI 10.1097/HP.0000000000001000
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    Zs.MO 253: Show issues

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  7. Article ; Online: O'Donoghue Recognized with Loevinger-Berman Award.

    Sgouros, George

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine

    2016  Volume 57, Issue 8, Page(s) 17N

    Language English
    Publishing date 2016-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80272-4
    ISSN 1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
    ISSN (online) 1535-5667
    ISSN 0097-9058 ; 0161-5505 ; 0022-3123
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    Zs.MO 328: Show issues

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  8. Article ; Online: Dale Recognized with Loevinger-Berman Award.

    Sgouros, George

    Journal of nuclear medicine : official publication, Society of Nuclear Medicine

    2015  Volume 56, Issue 9, Page(s) 22N

    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80272-4
    ISSN 1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
    ISSN (online) 1535-5667
    ISSN 0097-9058 ; 0161-5505 ; 0022-3123
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  9. Article ; Online: Large-scale in vitro microdosimetry via live cell microscopy imaging: implications for radiosensitivity and RBE evaluations in alpha-emitter radiopharmaceutical therapy.

    Bastiaannet, Remco / Liatsou, Ioanna / F Hobbs, Robert / Sgouros, George

    Journal of translational medicine

    2023  Volume 21, Issue 1, Page(s) 144

    Abstract: Background: Alpha-emitter radiopharmaceutical therapy (αRPT) has shown promising outcomes in metastatic disease. However, the short range of the alpha particles necessitates dosimetry on a near-cellular spatial scale. Current knowledge on cellular ... ...

    Abstract Background: Alpha-emitter radiopharmaceutical therapy (αRPT) has shown promising outcomes in metastatic disease. However, the short range of the alpha particles necessitates dosimetry on a near-cellular spatial scale. Current knowledge on cellular dosimetry is primarily based on in vitro experiments using cell monolayers. The goal of such experiments is to establish cell sensitivity to absorbed dose (AD). However, AD cannot be measured directly and needs to be modeled. Current models, often idealize cells as spheroids in a regular grid (geometric model), simplify binding kinetics and ignore the stochastic nature of radioactive decay. It is unclear what the impact of such simplifications is, but oversimplification results in inaccurate and non-generalizable results, which hampers the rigorous study of the underlying radiobiology.
    Methods: We systematically mapped out 3D cell geometries, clustering behavior, agent binding, internalization, and subcellular trafficking kinetics for a large cohort of live cells under representative experimental conditions using confocal microscopy. This allowed for realistic Monte Carlo-based (micro)dosimetry. Experimentally established surviving fractions of the HER2 + breast cancer cell line treated with a
    Results: In total, 567 cells were measured up to 26 h post-incubation. Realistic cell clustering had a large (2x), and cell geometry a small (16.4% difference) impact on AD, compared to the geometric model. Microdosimetry revealed that more than half of the cells do not receive any dose for most of the tested conditions, greatly impacting cell sensitivity estimates. Including these stochastic effects in the model, resulted in significantly more accurate predictions of surviving fraction and RBE (permutation test; p < .01).
    Conclusions: This comprehensive integration of the biological and physical aspects resulted in a more accurate method of cell survival modelling in αRPT experiments. Specifically, including realistic stochastic radiation effects and cell clustering behavior is crucial to obtaining generalizable radiobiological parameters.
    MeSH term(s) Humans ; Radiopharmaceuticals ; Relative Biological Effectiveness ; Microscopy ; Radiation Tolerance ; Radiobiology ; Radiometry/methods ; Monte Carlo Method
    Chemical Substances Radiopharmaceuticals
    Language English
    Publishing date 2023-02-24
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2118570-0
    ISSN 1479-5876 ; 1479-5876
    ISSN (online) 1479-5876
    ISSN 1479-5876
    DOI 10.1186/s12967-023-03991-1
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  10. Article ; Online: How Can Radiopharmaceutical Therapies Reach Their Full Potential? Improving Dose Reporting and Phase I Clinical Trial Design.

    Kiess, Ana P / O'Donoghue, Joseph / Uribe, Carlos / Bodei, Lisa / Hobbs, Robert F / Hesterman, Jacob / Kesner, Adam L / Sgouros, George

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2024  , Page(s) JCO2301241

    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.23.01241
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