A solid support generator of the Auger electron emitter rhodium-103m from [103Pd]palladium

Jensen, Andreas Tue Ingemann; Zhuravlev, Fedor; Severin, Gregory; Magnus, Charlotte Busk; Fonslet, Jesper; Köster, U.; Jensen, Mikael

doi:10.1016/j.apradiso.2019.108985

Cited by 10 publications

(4 citation statements)

References 21 publications

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“…The two employed instruments (LSC and Ge detector) were observed to measure radioactivity values with a factor 1.12 difference (Figure S10, Supporting Information), likely as a result of LSC detection of 103m Rh, the radioactive daughter of 103 Pd, and general counting efficiencies below 100% for each radionuclide on the LSC. This was in line with previous observations, [66] and was taken into account when comparing data.…”

Section: Methodssupporting

confidence: 92%

Effective Intratumoral Retention of [¹⁰³Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Fach

Fliedner

Kempen

et al. 2021

Adv Healthcare Materials

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Local application of radioactive sources as brachytherapy is well established in oncology. This treatment is highly invasive however, due to the insertion of millimeter sized metal seeds. The authors report the development of a new concept for brachytherapy, based on gold-palladium (AuPd) alloy nanoparticles, intrinsically radiolabeled with 103 Pd. These are formulated in a carbohydrate-ester based liquid, capable of forming biodegradable gel-like implants upon injection. This allows for less invasive administration through small-gauge needles. [ 103 Pd]AuPd nanoparticles with sizes around 20 nm are prepared with radiolabeling efficiencies ranging from 79% to >99%. Coating with the hydrophobic polymer poly(N-isopropylacrylamide) leads to nanoparticle diameters below 40 nm. Dispersing the nanoparticles in ethanol with water insoluble carbohydrate esters gives "nanogels", a low viscosity liquid capable of solidifying upon injection into aqueous environments. Both nanoparticles and radioactivity are stably retained in the nanogel over 25 days (>99%) after formation in aqueous buffers. Animals bearing CT26 murine tumors are injected intratumorally with 25 MBq of the 103 Pd-nanogel, and display tumor growth delay and significantly increase median survival times compared with control groups. Excellent retention in the tumor of both the 103 Pd and the nanoparticle matrix itself is observed, demonstrating a potential for replacing currently used brachytherapy seeds.

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Section: Methodssupporting

confidence: 92%

Effective Intratumoral Retention of [¹⁰³Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Fach

Fliedner

Kempen

et al. 2021

Adv Healthcare Materials

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“…This contrasts with previously published data for chelator-based in-vivo generators. Studies conducted on in vivo generators, such as 103 Pd/ 103m Rh (Jensen et al 2020 ), 166 Dy/ 166 Ho (Wang et al 2022 ) and 212 Pb/ 212 Bi (Mirzadeh et al 1993 ), have demonstrated that a significant percentage of daughter radionuclides are liberated when chelators are employed to immobilize parent radionuclides. According to (Wang et al 2022 ), the loss of daughter radionuclides was attributed to their de-excitation through the internal conversion, resulting in Auger electron emission, rather than to the recoil energy associated with the emission of ß - particles and neutrinos.…”

Section: Discussionmentioning

confidence: 99%

Au@109Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers: studies on the applicability of 109Pd/109mAg in vivo generator in combined β− auger electron therapy

Gharibkandi,

Wawrowicz,

Majkowska-Pilip

et al. 2023

EJNMMI radiopharm. chem.

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Background In radionuclide therapy, to enhance therapeutic efficacy, an intriguing alternative is to ensure the simultaneous implementation of low- and high-LET radiation emitted from a one radionuclide. In the present study, we introduce the concept of utilizing 109Pd (T1/2 = 13.7 h) in the form of a 109Pd/109mAg in vivo generator. In this system, 109Pd emits beta particles of medium energy, while 109mAg releases a cascade of conversion and Auger electrons. 109Pd was utilized in the form of 15 nm gold nanoparticles, which were coated with a monolayer of 109Pd. In this system, the 109Pd atoms are on the surface of the nanoparticle, while the 109mAg atoms generated in the decay reaction possess the capability for unhindered emission of Auger electrons. Results 109Pd, obtained through neutron irradiation of natural palladium, was deposited onto 15-nm gold nanoparticles, exceeding a efficiency rate of 95%. In contrast to previously published data on in vivo generators based on chelators, where the daughter radionuclide diffuses away from the molecules, daughter radionuclide 109mAg remains on the surface of gold nanoparticles after the decay of 109Pd. To obtain a radiobioconjugate with an affinity for HER2 receptors, polyethylene glycol chains and the monoclonal antibody trastuzumab were attached to the Au@Pd nanoparticles. The synthesized bioconjugate contained an average of 9.5 trastuzumab molecules per one nanoparticle. In vitro cell studies indicated specific binding of the Au@109Pd-PEG-trastuzumab radiobioconjugate to the HER2 receptor on SKOV-3 cells, resulting in 90% internalization. Confocal images illustrated the accumulation of Au@109Pd-PEG-trastuzumab in the perinuclear area surrounding the cell nucleus. Despite the lack of nuclear localization, which is necessary to achieve an effective cytotoxic effect of Auger electrons, a substantial cytotoxic effect, significantly greater than that of pure β− and pure Auger electron emitters was observed. We hypothesize that in the studied system, the cytotoxic effect of the Auger electrons could have also occurred through the damage to the cell’s nuclear membrane by Auger electrons emitted from nanoparticles accumulated in the perinuclear area. Conclusion The obtained results show that trastuzumab-functionalized 109Pd-labeled nanoparticles can be suitable for the application in combined β−—Auger electron targeted radionuclide therapy. Due to both components decay (β− and conversion/Auger electrons), the 109Pd/109mAg in vivo generator presents unique potential in this field. Despite the lack of nuclear localization, which is highly required for efficient Auger electron therapy, an adequate cytotoxic effect was attained.

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“…However, the range of soft radiometals relevant to theranostics is rarely investigated, due to a lack of well-suited bifunctional chelators with active chemical handles that can be practically conjugated to targeting vectors (Figure 1A). Suitable soft radiometals for AeRT include isotopes of platinum ( 193m Pt and 195m Pt) and rhodium ( 103m Rh) [21,22]. Additionally, 103 Pd and 105 Rh, an X-ray emitter and a beta particle emitter, respectively, also have potential use in TRT.…”

Section: Figure 1 (A) Bifunctionalmentioning

confidence: 99%

Novel bifunctional [16]aneS4-derived chelators for soft radiometals

Straathof¹,

Jensen²,

Zhuravlev³

2022

Nuclear Medicine and Biology

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A solid support generator of the Auger electron emitter rhodium-103m from [103Pd]palladium

Cited by 10 publications

References 21 publications

Effective Intratumoral Retention of [¹⁰³Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Effective Intratumoral Retention of [¹⁰³Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Au@109Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers: studies on the applicability of 109Pd/109mAg in vivo generator in combined β− auger electron therapy

Novel bifunctional [16]aneS4-derived chelators for soft radiometals

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A solid support generator of the Auger electron emitter rhodium-103m from [103Pd]palladium

Cited by 10 publications

References 21 publications

Effective Intratumoral Retention of [103Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Effective Intratumoral Retention of [103Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Au@109Pd core–shell nanoparticle conjugated to trastuzumab for the therapy of HER2+ cancers: studies on the applicability of 109Pd/109mAg in vivo generator in combined β− auger electron therapy

Novel bifunctional [16]aneS4-derived chelators for soft radiometals

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Effective Intratumoral Retention of [¹⁰³Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy

Effective Intratumoral Retention of [¹⁰³Pd]AuPd Alloy Nanoparticles Embedded in Gel‐Forming Liquids Paves the Way for New Nanobrachytherapy