WO2023077375A1 - Agent xrf in vivo - Google Patents

Agent xrf in vivo Download PDF

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Publication number
WO2023077375A1
WO2023077375A1 PCT/CN2021/128774 CN2021128774W WO2023077375A1 WO 2023077375 A1 WO2023077375 A1 WO 2023077375A1 CN 2021128774 W CN2021128774 W CN 2021128774W WO 2023077375 A1 WO2023077375 A1 WO 2023077375A1
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WO
WIPO (PCT)
Prior art keywords
imaging agent
agent
imaging
metal
ray
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Application number
PCT/CN2021/128774
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English (en)
Inventor
Peiyan CAO
Yurun LIU
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Shenzhen Xpectvision Technology Co., Ltd.
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Publication date
Application filed by Shenzhen Xpectvision Technology Co., Ltd. filed Critical Shenzhen Xpectvision Technology Co., Ltd.
Priority to PCT/CN2021/128774 priority Critical patent/WO2023077375A1/fr
Priority to TW111136903A priority patent/TW202319071A/zh
Publication of WO2023077375A1 publication Critical patent/WO2023077375A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations

Definitions

  • the disclosure herein relates to X-ray detection, including detection of X-ray fluorescence (XRF) , and more particularly in vivo agents for XRF imaging and systems and methods for XRF imaging using in vivo agents.
  • XRF X-ray fluorescence
  • X-ray detectors may be devices used to measure the flux, spatial distribution, spectrum, or other properties of X-rays.
  • X-ray detectors may be used for many applications.
  • One important application is imaging.
  • X-ray imaging is a radiography technique and can be used to reveal the internal structure of a non-uniformly composed and opaque object such as the human body.
  • X-ray fluorescence is the emission of characteristic fluorescent X-rays from a material that has been excited by, for example, exposure to high-energy X-rays or gamma rays.
  • An electron on an inner orbital of an atom may be ejected, leaving a vacancy on the inner orbital, if the atom is exposed to X-rays or gamma rays with photon energy greater than the ionization potential of the electron.
  • an X-ray fluorescent X-ray or secondary X-ray
  • the emitted X-ray has a photon energy equal the energy difference between the outer orbital and inner orbital electrons.
  • the number of possible relaxations is limited.
  • Fig. 1A when an electron on the L orbital relaxes to fill a vacancy on the K orbital (L ⁇ K) , the fluorescent X-ray is called K ⁇ .
  • the fluorescent X-ray from M ⁇ K relaxation is called K ⁇ .
  • Fig. 1B the fluorescent X-ray from M ⁇ L relaxation is called L ⁇ , and so on.
  • Analyzing the fluorescent X-ray spectrum can identify the elements in a sample because each element has orbitals of characteristic energy.
  • the fluorescent X-ray can be analyzed either by sorting the energies of the photons (energy-dispersive analysis) or by separating the wavelengths of the fluorescent X-ray (wavelength-dispersive analysis) .
  • the intensity of each characteristic energy peak is directly related to the amount of each element in the sample.
  • Proportional counters or various types of solid-state detectors may be used in energy dispersive analysis. These detectors are based on the same principle: an incoming X-ray photon ionizes a large number of detector atoms with the amount of charge carriers produced being proportional to the energy of the incoming X-ray photon. The charge carriers are collected and counted to determine the energy of the incoming X-ray photon and the process repeats itself for the next incoming X-ray photon. After detection of many X-ray photons, a spectrum may be compiled by counting the number of X-ray photons as a function of their energy. The speed of these detectors is limited because the charge carriers generated by one incoming X-ray photon must be collected before the next incoming X-ray hits the detector.
  • Wavelength dispersive analysis typically uses a photomultiplier.
  • the X-ray photons of a single wavelength are selected from the incoming X-ray a monochromator and are passed into the photomultiplier.
  • the photomultiplier counts individual X-ray photons as they pass through.
  • the counter is a chamber containing a gas that is ionizable by X-ray photons.
  • a central electrode is charged at (typically) +1700 V with respect to the conducting chamber walls, and each X-ray photon triggers a pulse-like cascade of current across this field.
  • the signal is amplified and transformed into an accumulating digital count. These counts are used to determine the intensity of the X-ray at the single wavelength selected.
  • An imaging agent suitable for in vivo X-ray fluorescence imaging may comprise a metal selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium.
  • the imaging agent may be represented by the formula XMO n , wherein X represents an alkali metal selected from the group consisting of Lithium, Sodium, Potassium, and Rubidium; M represents the metal selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium; and O represents Oxygen.
  • the imaging agent may comprise a chelating agent, such as exametazime.
  • the imaging agent may be a metabolite that includes a metal selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium.
  • the imaging agent may comprise an alkali metal cation bonded to a metal selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium to form a salt.
  • the imaging agent may be derived from a salt of an alkali metal cation bonded to a metal selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium.
  • the imaging agent may be non-radioactive.
  • An image forming method may comprise: administering a dose of the imaging agent to a subject, wherein the subject is an organism; projecting a radiation beam onto the subject, thereby causing emission of X-rays from the imaging agent; and detecting the X-rays by counting X-ray photons incident on a semiconductor X-ray detector.
  • the imaging agent may be administered orally, by injection, or intravenously.
  • An imaging agent suitable for in vivo X-ray fluorescence imaging may comprise: a compound selected from the group consisting of LiZrO n , LiNbO n , LiMoO n , LiRuO n , LiRhO n , NaZrO n , NaNbO n , NaMoO n , NaRuO n , NaRhO n , KZrO n , KNbO n , KMoO n , KRuO n , KRhO n , RbZrO n , RbNbO n , RbMoO n , RbRuO n , RbRhO n , CsZrO n , CsNbO n , CsMoO n , CsRuO n , CsRhO n , FrZrO n , FrNbO n , FrMo
  • Fig. 1A schematically shows a mechanism of XRF.
  • Fig. 1B schematically shows a mechanism of XRF.
  • Fig. 1C schematically shows an image forming method according to an embodiment.
  • Fig. 2A schematically shows aspects of image forming systems and methods according to various embodiments.
  • Fig. 2B schematically shows aspects of image forming systems and methods according to various embodiment.
  • Fig. 1C schematically shows an image forming method 100 according to an embodiment.
  • Figs. 2A and 2B schematically show aspects of the method 100 and an image forming system 200 for forming an image according to an embodiment.
  • the method 100 includes: administering S101 a dose of an imaging agent 210 to a subject 220, wherein the subject 220 is an organism, such as a human; projecting S103 a radiation beam 230 onto the subject 220, thereby causing the imaging agent 210 to emit X-rays 240; and detecting S105 the X-rays 240 by counting X-ray photons incident on a semiconductor X-ray detector 250.
  • Fig. 2A schematically shows the administering S101 the dose of the imaging agent 210 to the subject 220.
  • the administering S101 the dose of the imaging agent 210 is by oral administration to the subject 220, by injection, or by intravenous administration.
  • the dose of the imaging agent 210 is administered in other ways.
  • Fig. 2B schematically shows an embodiment of the projecting S103 the radiation beam 230 onto the subject 220.
  • the imaging agent 210 is inside the subject 220.
  • X-ray fluorescence XRF
  • the radiation beam 230 ejects the electron, leaving a vacancy on the inner orbital.
  • an X-ray (fluorescent X-ray or secondary X-ray) 240 is emitted.
  • the emitted X-ray 240 has a photon energy equal to the energy difference between the outer orbital and the inner orbital electrons.
  • the semiconductor X-ray detector 250 counts the X-ray photons 240 incident on the X-ray detector 250.
  • the imaging agent 210 comprises a metal M selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium.
  • the imaging agent 210 is represented by the formula XMO n , wherein M represents the metal from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium; O n represents n Oxygen atoms; and X represents an alkali metal.
  • the alkali metal is selected from the group consisting of Lithium, Sodium, Potassium, and Rubidium
  • the imaging agent 210 comprises a ligand bonded to the metal M to form a coordination complex.
  • the ligand is a chelating agent, for example, exametazime.
  • the imaging agent 210 is a metabolite that includes the metal M.
  • the imaging agent 210 comprises an alkali metal cation bonded to the metal M to form a salt.
  • the alkali metal is selected from the group consisting of Lithium, Sodium, Potassium, and Rubidium.
  • the imaging agent 210 is derived from a salt of an alkali metal cation and the metal M.
  • the alkali metal cation is selected from the group consisting of Lithium, Sodium, Potassium, and Rubidium.
  • the metal M is selected from the group consisting of Zirconium, Niobium, Molybdenum, Ruthenium, and Rhodium.
  • the imaging agent 210 is not radioactive.
  • the imaging agent 210 comprises a compound selected from the group consisting of LiZrO n , LiNbO n , LiMoO n , LiRuO n , LiRhO n , NaZrO n , NaNbO n , NaMoO n , NaRuO n , NaRhO n , KZrO n , KNbO n , KMoO n , KRuO n , KRhO n , RbZrO n , RbNbO n , RbMoO n , RbRuO n , RbRhO n , CsZrO n , CsNbO n , CsMoO n , CsRuO n , CsRhO n , FrZrO n , FrNbO n , FrMoO n , FrRuO n , FrN

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  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Luminescent Compositions (AREA)

Abstract

Agent d'imagerie (210) convenant pour une fluorescence par rayons X in vivo (XRF) est représenté par la formule XMOn. X représente un métal alcalin. M représente un métal, à savoir, le zirconium, le niobium, le molybdène, le ruthénium, ou le rhodium. On représente un nombre entier n d'atomes d'oxygène. Les procédés d'imagerie XRF comprennent l'administration de l'agent d'imagerie (210) à un sujet (220) par voie orale, par injection, ou par voie intraveineuse (S101). Un faisceau de rayonnement (230) projeté sur le sujet (220) provoque l'émission de rayons X (240) depuis l'agent d'imagerie (210) administré au sujet (220) (S103). Les rayons X (240) émis depuis l'agent d'imagerie (210) sont détectés par un détecteur de rayons X à semi-conducteur (250) pour former une image (S105). L'agent d'imagerie (210) comprend un composé sélectionné dans le groupe constitué de LiZrOn, LiNbOn, LiMoOn, LiRuOn, LiRhOn, NaZrOn, NaNbOn, NaMoOn, NaRuOn, NaRhOn, KZrOn, KNbOn, KMoOn, KRuOn, KRhOn, RbZrOn, RbNbOn, RbMoOn, RbRuOn, RbRhOn, CsZrOn, CsNbOn, CsMoOn, CsRuOn, CsRhOn, FrZrOn, FrNbOn, FrMoOn, FrRuOn, et FrRhOn.
PCT/CN2021/128774 2021-11-04 2021-11-04 Agent xrf in vivo WO2023077375A1 (fr)

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Application Number Priority Date Filing Date Title
PCT/CN2021/128774 WO2023077375A1 (fr) 2021-11-04 2021-11-04 Agent xrf in vivo
TW111136903A TW202319071A (zh) 2021-11-04 2022-09-29 顯像劑及影像形成方法

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PCT/CN2021/128774 WO2023077375A1 (fr) 2021-11-04 2021-11-04 Agent xrf in vivo

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101678118A (zh) * 2006-10-05 2010-03-24 得克萨斯大学体系董事会 用于核成像和放射疗法的螯合剂的有效合成：组合物和应用
CN103442737A (zh) * 2011-01-20 2013-12-11 得克萨斯系统大学董事会 Mri标记、递送和提取系统及其制造方法和用途
CN104321083A (zh) * 2012-03-26 2015-01-28 得克萨斯大学体系董事会 用于成像和治疗的亚乙双半胱氨酸-糖缀合物的有效合成
WO2020208631A1 (fr) * 2019-04-08 2020-10-15 Convergent R.N.R Ltd. Système et procédé d'optimisation de radiothérapies
CN112074234A (zh) * 2018-05-21 2020-12-11 深圳帧观德芯科技有限公司 用于对前列腺进行成像的装置
CN112739264A (zh) * 2018-07-30 2021-04-30 森瑟实验室有限责任公司 用于x射线成像的系统和方法以及造影剂

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101678118A (zh) * 2006-10-05 2010-03-24 得克萨斯大学体系董事会 用于核成像和放射疗法的螯合剂的有效合成：组合物和应用
CN103442737A (zh) * 2011-01-20 2013-12-11 得克萨斯系统大学董事会 Mri标记、递送和提取系统及其制造方法和用途
CN104321083A (zh) * 2012-03-26 2015-01-28 得克萨斯大学体系董事会 用于成像和治疗的亚乙双半胱氨酸-糖缀合物的有效合成
CN112074234A (zh) * 2018-05-21 2020-12-11 深圳帧观德芯科技有限公司 用于对前列腺进行成像的装置
CN112739264A (zh) * 2018-07-30 2021-04-30 森瑟实验室有限责任公司 用于x射线成像的系统和方法以及造影剂
WO2020208631A1 (fr) * 2019-04-08 2020-10-15 Convergent R.N.R Ltd. Système et procédé d'optimisation de radiothérapies

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