Production of 191Pt from an iridium target by vertical beam irradiation and simultaneous alkali fusion

Obata, Honoka; Minegishi, Katsuyuki; Nagatsu, Kotaro; Zhang, Ming‐Rong; Shinohara, Atsushi

doi:10.1016/j.apradiso.2019.04.007

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…189, 191 Pt was produced via the nat Ir(p, xn) 189, 191 Pt reaction in a 30 MeV proton beam for 2–3 h at a beam current of 10 μA at the NIRS-QST isochronous cyclotron AVF-930, as described previously [ 30 , 31 ]. We used mixed 189, 191 Pt, described as radio-Pt because 189 Pt ( T 1/2 = 10.87 h, EC) is co-produced along with 191 Pt ( T 1/2 = 2.83 d, EC) from a natural Ir target.…”

Section: Methodsmentioning

confidence: 99%

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In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

Obata

Tsuji

Sudo

et al. 2021

IJMS

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Due to their short-range (2–500 nm), Auger electrons (Auger e−) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e−, it remains challenging to maximize the interaction between Auger e− and DNA. To assess the DNA-damaging effect of Auger e− released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e− very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e−.

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Section: Methodsmentioning

confidence: 99%

“…Recently, we established a procedure for producing n.c.a. [ 189, 191 Pt]cisplatin (described as radio-cisplatin) [ 30 , 31 ]. The theoretical molar activity of the n.c.a.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

Obata

Tsuji

Sudo

et al. 2021

IJMS

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“…A gamma-counter (Wizard2 2-Detector Gamma Counter; PerkinElmer, Waltham, MA, USA) was used to measure radioactivity in biological samples. 189,191 Pt]cisplatin 189,191 Pt was produced via the nat Ir(p, xn) 189,191 Pt reaction in a 30 MeV proton beam for 2-3 h at a beam current of 10 μA at the NIRS-QST isochronous cyclotron AVF-930, as described previously [30][31]. We used mixed 189,191 Pt, described as radio-Pt because 189 Pt (T1/2=10.87 h, EC) is co-produced along with 191 Pt (T1/2=2.83 d, EC) from a natural Ir target.…”

Section: Generalmentioning

confidence: 99%

In Vitro Evaluation of No-carrier-added Radiolabeled Cisplatin ([<sup>189, 191</sup>Pt]cisplatin) Emitting Auger Electrons

Obata¹,

Tsuji²,

Sudo³

et al. 2021

Preprint

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Due to their short range (2–500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Au-ger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by im-munofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incuba-tion), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.

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“…In general, Auger therapy has been investigated and revealed a high potential for cancer treatment [27,28,29]. To give a concrete example, Auger therapy using 191 Pt-doped cisplatin is expected to be much more effective than monotherapy [30,31]. Nevertheless, the production of 191 Pt, 193 m Pt and 195 Pt in appropriate qualities and quantities is challenging and still has to be discovered [25,32,33,34,35].…”

Section: Introductionmentioning

confidence: 99%

Cisplatin – A more Efficient Drug in Combination with Radionuclides?

et al. 2022

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Aim The combination of conventional chemotherapeutic drugs with radionuclides or external radiation is discussed for a long period of time. The major advantage of a successful combination therapy is the reduction of severe side effects by decreasing the needed dose and simultaneously increasing therapeutic efficiency. Methods In this study, pUC19 plasmid DNA was incubated with the cytostatic drug cisplatin and additionally irradiated with 99mTc, 188Re and 223Ra. To verify the contribution of possibly excited platinum atoms to the emission of Auger electrons we determined DNA damages, such as single- and double strand breaks. Results The threshold concentration value of cisplatin, which was tolerated by pUC19 plasmid DNA was determined to be 18–24 nM. Nevertheless, even at higher dose values (>100 Gy) and simultaneous incubation of cisplatin to 200 ng plasmid DNA, no significant increase in the number of induced single- and double-strand breaks was obtained, compared to the damage solely caused by the radionuclides. Conclusion We thereby conclude that there is no direct dependence of the mechanism of strand break induction to the absence or presence of platinum atoms attached to the DNA. Reported increasing DNA damages in therapy approaches on a cellular level strongly depend on the study design and are mainly influenced by repair mechanisms in living cells. Nevertheless, the use of radioactive cisplatin, containing the Auger electron emitter 191Pt, 193mPt or 195mPt, is a bright prospect for future therapy by killing tumor cells combining two operating principles: a cytostatic drug and a radiopharmaceutical at the same time.

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Production of 191Pt from an iridium target by vertical beam irradiation and simultaneous alkali fusion

Cited by 8 publications

References 23 publications

In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

In Vitro Evaluation of No-carrier-added Radiolabeled Cisplatin ([<sup>189, 191</sup>Pt]cisplatin) Emitting Auger Electrons

Cisplatin – A more Efficient Drug in Combination with Radionuclides?

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