Photonuclear production of <sup>193m,195m</sup>Pt and synthesis of radioactive cisplatin

Dykiy, Mikola P.; Dovbnya, A.; Lyashko, Yuriy V.; Medvedeva, E.P.; Medvedev, D. V.; Uvarov, V.L.

doi:10.1002/jlcr.1210

Cited by 15 publications

(4 citation statements)

References 2 publications

(1 reference statement)

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“…195m Pt decay results in a larger number of AEs and a high energy per decay compared to other commonly used AE emitters such as 125 I and 111 In (Table 1). 195m Pt produced from irradiation of 197 Au in a high current linear accelerator [ 197 Au(γ,np) 195m Pt] was extracted and used to synthesise 195m Pt-cisplatin with a high specific activity of up to 3.7 TBq/mg by Bodnar and colleagues (Dykiy et al 2007; Bodnar et al 2015). Treatment of Ehrlich adenocarcinoma cells in vitro with 0.017 pg/mL 195m Pt-cisplatin reduced cell viability to 3% within 6 h, an approximate 8-fold reduction compared to 7.5 μg/mL treatment with nonradioactive cisplatin, which decreased cell viability to only 25% (Bodnar et al 2015).…”

Section: Preclinical Studiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

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Background: Auger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g. 111 In, 67 Ga, 99m Tc, 195m Pt, 125 I and 123 I). This energy is deposited over nanometre-micrometre distances, resulting in high linear energy transfer (LET) that is potent for causing lethal damage in cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for treatment of cancer. In this review, we describe the radiobiological properties of AEs, their radiation dosimetry, radiolabelling methods, and preclinical and clinical studies that have been performed to investigate AEs for cancer treatment. Results: AEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA (e.g. 125 I-IUdR). AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane, and kill non-targeted cells through a cross-dose or bystander effect. The radiation dosimetry of AEs considers both organ doses and cellular doses. The Medical Internal Radiation Dose (MIRD) schema may be applied. Radiolabelling methods for complexing AE-emitters to biomolecules (antibodies and peptides) and nanoparticles include radioiodination (125 I and 123 I) or radiometal chelation (111 In, 67 Ga, 99m Tc). Cancer cells exposed in vitro to AE-emitting radiotherapeutic agents exhibit decreased clonogenic survival correlated at least in part with unrepaired DNA double-strand breaks (DSBs) detected by immunofluorescence for γH2AX, and chromosomal aberrations. Preclinical studies of AE-emitting radiotherapeutic agents have shown strong tumour growth inhibition in vivo in tumour xenograft mouse models. Minimal normal tissue toxicity was found due to the restricted toxicity of AEs mostly on tumour cells targeted by the radiotherapeutic agents. Clinical studies of AEs for cancer treatment have been limited but some encouraging results were obtained in early studies using 111 In-DTPAoctreotide and 125 I-IUdR, in which tumour remissions were achieved in several patients at administered amounts that caused low normal tissue toxicity, as well as promising improvements in the survival of glioblastoma patients with 125 I-mAb 425, with minimal normal tissue toxicity. Conclusions: Proof-of-principle for AE radiotherapy of cancer has been shown preclinically, and clinically in a limited number of studies. The recent introduction of many biologically-targeted therapies for cancer creates new opportunities to design novel AE-emitting agents for cancer treatment. Pierre Auger did not conceive of the application of AEs for targeted cancer treatment, but this is a tremendously exciting future that we and many other scientists in this field envision.

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Section: Preclinical Studiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

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“…The half-lives of 197 Pt and 194 Ir are relatively short, so allowing 2 days of decay postirradiation increases 195m Pt to 77% of the total radioactivity. Higher-specific-activity 195m Pt can be prepared by the 192 Os(α,n) 195m Pt reaction using 18–24 MeV α particles or by the 197 Au(γ,np) 195m Pt reaction . The comparatively low specific activity is not a limiting factor for biological studies of Pt-based chemotherapeutics because the administered doses of these drugs are typically on the order of tens to hundreds of mg.…”

Section: Platinummentioning

confidence: 99%

Radioactive Transition Metals for Imaging and Therapy

2018

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Nuclear medicine is composed of two complementary areas, imaging and therapy. Positron emission tomography (PET) and single-photon imaging, including single-photon emission computed tomography (SPECT), comprise the imaging component of nuclear medicine. These areas are distinct in that they exploit different nuclear decay processes and also different imaging technologies. In PET, images are created from the 511 keV photons produced when the positron emitted by a radionuclide encounters an electron and is annihilated. In contrast, in single-photon imaging, images are created from the γ rays (and occasionally X-rays) directly emitted by the nucleus. Therapeutic nuclear medicine uses particulate radiation such as Auger or conversion electrons or β − or α particles. All three of these technologies are linked by the requirement that the radionuclide must be attached to a suitable vector that can deliver it to its target. It is imperative that the radionuclide remain attached to the vector before it is delivered to its target as well as after it reaches its target or else the resulting image (or therapeutic outcome) will not reflect the biological process of interest. Radiochemistry is at the core of this process, and radiometals offer radiopharmaceutical chemists a tremendous range of options with which to accomplish these goals. They also offer a wide range of options in terms of radionuclide half-lives and emission properties, providing the ability to carefully match the decay properties with the desired outcome. This Review provides an overview of some of the ways this can be accomplished as well as several historical examples of some of the limitations of earlier metalloradiopharmaceuticals and the ways that new technologies, primarily related to radionuclide production, have provided solutions to these problems.

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“…The production of platinum-195m in the (,`) reaction consists of the recoil nucleus gains insignificant energy. The platinum-195m yield in the 196 Pt(,n) 195m Pt reaction was calculated with the help of the program complex PENELOPE [4].…”

Section: Methodsmentioning

confidence: 99%

MECHANISMS OF MORPHOLOGY DEATH OF TUMOR CELL BY EFFECT NON-RADIOACTIVE AND RADIOACTIVE 195mPt-CISPLATIN

Dikiy¹,

Lyashko²,

Medvedeva³

et al. 2021

Problems of Atomic Science and Technology

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The photonuclear technology of preparation radioactive cisplatin 195mPt was been developed by the bremsstrahlung from the electron accelerators. In the novel technology, the production of 195mPt from reaction 197Au(γ,np)195mPt with a high specific activity >1 Ci/mg-1 was realized. The Ehrlich adenocarcinoma cells were been used as a neoplastic model. There are two groups: 1. tumor cells with non-radioactive cisplatin; 2. tumor cells with radioactive cisplatin (0.17 pg 195mPt-cisplatin). The number of morphology death cells as a result of radioactive cisplatin action was more than after action of non-radioactive cisplatin. The different mechanisms of the morphology death cell (necrosis for non-radioactive and apoptosis for radioactive) were detected.

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Photonuclear production of ^193m,195mPt and synthesis of radioactive cisplatin

Cited by 15 publications

References 2 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Radioactive Transition Metals for Imaging and Therapy

MECHANISMS OF MORPHOLOGY DEATH OF TUMOR CELL BY EFFECT NON-RADIOACTIVE AND RADIOACTIVE 195mPt-CISPLATIN

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Photonuclear production of 193m,195mPt and synthesis of radioactive cisplatin

Cited by 15 publications

References 2 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Radioactive Transition Metals for Imaging and Therapy

MECHANISMS OF MORPHOLOGY DEATH OF TUMOR CELL BY EFFECT NON-RADIOACTIVE AND RADIOACTIVE 195mPt-CISPLATIN

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Photonuclear production of ^193m,195mPt and synthesis of radioactive cisplatin