Auger therapy

Auger therapy is a form of radiation therapy for the treatment of cancer which relies on a large number of low-energy electrons (emitted by the Auger effect) to damage cancer cells, rather than the high-energy radiation used in traditional radiation therapy. Similar to other forms of radiation therapy, Auger therapy relies on radiation-induced damage to cancer cells (particularly DNA damage) to arrest cell division, stop tumor growth and metastasis and kill cancerous cells. It differs from other types of radiation therapy in that electrons emitted via the Auger effect (Auger electrons) are released in large numbers with low kinetic energy. Auger therapy is a form of radiation therapy for the treatment of cancer which relies on a large number of low-energy electrons (emitted by the Auger effect) to damage cancer cells, rather than the high-energy radiation used in traditional radiation therapy. Similar to other forms of radiation therapy, Auger therapy relies on radiation-induced damage to cancer cells (particularly DNA damage) to arrest cell division, stop tumor growth and metastasis and kill cancerous cells. It differs from other types of radiation therapy in that electrons emitted via the Auger effect (Auger electrons) are released in large numbers with low kinetic energy. Because of their low energy, these electrons damage cells over a very short range: less than the size of a single cell, on the order of nanometers. This very short-range delivery of energy permits highly targeted therapies, since the radiation-emitting nuclide is required to be inside the cell to cause damage to its nucleus. However, this is a technical challenge; Auger therapeutics must enter their cellular targets to be most effective. Auger therapeutics are small molecules, capable of entering cells of interest and binding to specific sub-cellular components, which contain one (or more) heavy atoms capable of emitting Auger electrons by radioactive decay or external excitation. The electron energy in a vacuum may be accurately measured with an electron detector in a Faraday cage, where the bias 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 zigzag path whose termination distance must be considered statistically and from differential measurements of higher-energy electrons at a much higher range. A 20 eV electron in water, for example, could have a range of 20 nm for 103 Gy 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 water for an electron using a Monte Carlo random walk 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. With a large, localized dose in situ 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 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. 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 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 oxided and used as BrdU. Before oxiding, 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 arsenic, with the addition of an alpha particle in a particle accelerator to form 77Br (with a half-life of 57 hours from its K-electron's capture by a proton from an unstable nucleus. This creates a K hole in Br, leading to its Auger cascade and disrupting the herpes gene without killing the cell. This experiment was performed during the 1970s at Memorial Sloan Kettering Cancer Center by Lawrance Helson and C. G. Wang, using 10 neuroblastoma cell cultures, Two cultures were successful in terminating the cell replication with 77Br in vitro, and the experiments were followed by a group of nude mice with implanted tumors. The in vivo mouse experiments were complicated when the mouse livers cleaved off the sugar component of BrdC rendering the mammalian and herpes genes to incorporate the 77Br-containing base, making no distinction between them. However, the Auger dose with 77BrdC disrupted the herpes-specific gene in several transformed cell cultures. The stain rose bengal may be ingested with minimal toxicity. Its red molecules contain four iodine atoms each; when they are diffused into cells (particularly transformed cells), they are absorbed by lysosomes attached at the Golgi apparatus.Lysosomes are small sacs of hydrolytic enzymes in the cytoplasm at a pH of 5, which were discovered by Christian de Duve with centrifugation to separate the cellular components. In normal cellular functions, lysosomes and proteasomes would digest a variety of discarded cellular components or molecules. With rose bengal distributed in the lysosome sac, the Auger dose induced by the inner shell ionization of iodine would disrupt the acidic sacs and alter the pH of the cytoplasm (localized chemotherapy).