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electrons, at under 1 keV they would be too soft to penetrate tissue sufficiently for therapy. Mid-range or heavy atoms (from bromine to platinum, for example) which could be induced by sufficiently hard X-ray photons to generate enough electrons to provide low-energy charges in an Auger cascade, will be considered for therapy.
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nearly the same ionic radius and location (at the 5th position for BrdU, which has an oxygen molecule at the top). Therefore, BrdC could be oxidized and used as BrdU. Before oxidation, BrdC was unusable as dC or dU in mammalian cells (except for the herpes gene, which could incorporate the BrdC). The bromine atom is made from
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placed on the cage will accurately define the particle energy reaching the detector. The range of low-energy electrons in tissue or water, particularly electrons at the nanometer scale, cannot be easily measured; it must be inferred, since low-energy electrons scatter at large angles and travel in a
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When a normal cell transforms, replicating uncontrollably, many unusual genes (including viral material such as herpes genes which are not normally expressed) are expressed with viral-specific functions. The molecule proposed to disrupt the herpes gene is BrdC, where Br replaces a methyl (CH3) with
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will be in close proximity to the delivery site (e.g., a DNA strand) to cause cytotoxicity. However, this is a technical challenge; Auger therapeutics must enter their cell-nuclear targets to be most effective. Auger therapeutics are radiolabelled biomolecules, capable of entering cells of interest
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or 5 nm for 104.7 Gy. For a group of 9–12 Auger electrons with energies at 12–18 eV in water (including the effect of water ionization at approximately 10 eV), an estimate of 106 Gy is probably sufficiently accurate. The illustration shows the simulated dose calculation in
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for molecular modification, the most obvious target molecule is the DNA duplex (where the complementary strands are separated by several nanometers). However, DNA duplex atoms are light elements (with only a few electrons each). Even if they could be induced by a photon beam to deliver Auger
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and binding to specific sub-cellular components. These typically carry a radioactive atom capable of emitting Auger electrons. The Auger electron emission from the atom is stimulated by radioactive decay, or by external pst (primary system therapy, such as X-ray) excitation.
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Simulated radiation dose of an electron in water, where the ionization energy of water at ~10 eV shows a resonant dose enhancement. The upper and lower curves are the short and long limiting ranges, respectively. In a vacuum, the kinetic energy
337:. Entering a cell with a low NaCl concentration, the aqua-chloride group would detach from the compound (allowing the missing chloride to link the G-G or A-G bases and bend the DNA helixes 45 degrees, damaging them). Although
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The aqua-Cl rationale, detaching the chloride atom from the cisplatin when it enters a cell and binding them to G-G or A-G adducts in the major grooves of the DNA helixes, could be applied to other metals—such as
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Hannon, Michael J. "Metal-based
Anticancer Drugs: From a past anchored in platinum chemistry to a post-genomic future of diverse chemistry and biology", Pure Appl. Chem. Vol.79, No. 12 pp 2243-2261, 2007.
353:) depending on the compressed thickness of the breast and delivering a high-contrast image. Although ruthenium is lighter than platinum, it can be induced to provide an Auger dose
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which gives up to 0.1 MGy. For a moderately-heavy atom to yield a dozen or more Auger electrons from its inner-shell ionization, the Auger dose becomes 106 Gy per event.
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as a typical synchrotron. A Coolidge X-ray tube brightens by 1.7 kVp and synchrotron brightness decreases by 4 kV, implying that it is not useful for Auger therapy.
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energy must be 30 keV or higher to penetrate tissue in therapeutic applications. Although synchrotron radiation is extremely bright and monochromatic without thermal
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Due to their low kinetic energy, emitted Auger electrons travel over a very short range: way less than the size of a single cell, on the order of less than a few-hundred
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zigzag path whose termination distance must be considered statistically and from differential measurements of higher-energy electrons at a much higher range. A 20
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compound (on the same side) is composed of a square molecule with two chloride atoms on one side and two ammonia groups on the other side, centered around the heavy
305:-containing base, making no distinction between them. However, the Auger dose with 77BrdC disrupted the herpes-specific gene in several transformed cell cultures.
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is captured by a proton in an unstable nucleus, creating a K hole in Br, and leading to its Auger cascade and disrupting the herpes gene without killing the cell.
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Sastry, KSR. Biological effects of Auger emitter iodine-125. A review. Report No. 1 of AAPM Nuclear medicine Task Group No. 6. Med. Phys. 19(6), 1361-1383, 1992.
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mouse experiments were complicated when the mouse livers cleaved off the sugar component of BrdC rendering the mammalian and herpes genes to incorporate the
349:(Ru)-chemically similar to platinum. Ruthenium is used to coat the anode target of a mammography X-ray tube, enabling operation at any voltage (22–28
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are used in as much as 70 percent of all chemotherapy, they are not particularly effective against certain cancers (such as breast and prostate tumors).
105:. In contrast to traditional α- and β-particle emitters, Auger electron emitters exhibit low cellular toxicity during transit in blood or bone marrow.
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used in traditional radiation therapy. Similar to other forms of radiation therapy, Auger therapy relies on radiation-induced damage to cancer
455:
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Persson, L. The Auger
Electron Effect in Radiation Dosimetry–A Review. Swedish Radiation Protection Institute, S-17116 Stockholm, Sweden.
317:, one of the leading agents in clinical use. Cisplatin acts by binding to DNA, forming one or two intrastrand cross-links of the G-G
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390:, its brightness falls off at the fourth power of photon energy. At 15–20 kV or higher an X-ray tube with a
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and kill cancerous cells. It differs from other types of radiation therapy in that electrons emitted via the
149: = 1 eV implies an electron velocity of 6×10 cm/s, or 0.2 percent of the speed of light.
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with resonant scattering from a moderately-heavy atom with dozens of electrons, the X-ray
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The electron energy in a vacuum may be accurately measured with an electron detector in a
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electron in water, for example, could have a range of 20 nm for 103
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Wang, CG; US Patent 8,278,315; "Radiotherapy Method using X-rays"; 2012.
255:, Two cultures were successful in terminating the cell replication with
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Knapp, Jr., F. F. (Russ) (2016). "2.5 Low-Energy
Electron Emitters".
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at 70% and the A-G adduct at ~20% of the major grooves of the
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J.Messungnoenab et al, Radiation
Research 158, 657-660; 2002
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Bromine electrons disrupting herpes-specific gene expression
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or from the preferred transmission X-ray tubes. To induce
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The group of metal-based anticancer drugs originated with
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by
Lawrance Helson and C. G. Wang, using 10 neuroblastoma
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Cancer therapy with Auger electrons: are we almost there?
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to the DNA adducts and deliver localized chemotherapy.
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X-ray tube with transmission target for line emissions
73:) to damage cancer cells, rather than the high-energy
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Monochromatic X-rays to induce inner-shell ionization
486:Giacomo Pirovano, Thomas C. Wilson, Thomas Reiner,
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276:, and the experiments were followed by a group of
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477:Journal of Nuclear Medicine, 44(9) 1479-1481.
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370:Monochromatic X-rays may be channeled from
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101:(Auger electrons) are released with low
488:Auger: The future of precision medicine
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249:Memorial Sloan Kettering Cancer Center
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309:DNA-targeted dose using cisplatin
439:Radiopharmaceuticals for Therapy
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190:With a large, localized dose
415:Targeted tumor radiotherapy
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