Pharmaceuticals and apparatus providing diagnosis and selective tissue necrosis

Abstract

Pharmaceuticals and Apparatus used in combination for diagnosis and tissue necrosis applicable to provide effective and selective therapy using the Mossbauer absorption phenomenon. Selected pharmaceutical compounds containing a radiation absorber isotope are administered to a tissue and excited by a radiation source which provides energy at the corresponding resonant Mossbauer absorption frequency of isotope containing pharmaceutical, where excitation effects nuclear transitions to cause highly selective energy absorption in the selected target tissue. For diagnostic purposes, de-excitation fluorescence of the isotope is monitored. For therapeutic purposes, the energy is converted to particle radiation by the isotope at the target tissue by internal conversion followed by an Auger electron cascade which results in radiolysis of DNA resulting in lethal double strand breaks in the DNA molecules of the target tissue. The tissue selectivity is achieved by providing a Mossbauer absorption frequency of the target tissue which differs from that of surrounding tissue. The difference in frequency is due to the properties of the pharmaceutical, and/or an imposition of external magnetic fields or narrow beam ultrasonic power at the site of the target tissue. The magnitude of radiation absorption at the resonant Mossbauer frequency for the target tissue is of the order of one million times the absorption of surrounding nontarget tissue, which has a different Mossbauer absorption frequency, thereby producing considerably reduced side effects in comparison to conventional chemotherapy or radiation therapy.

What is claimed is:  
     
         1 . A compound comprising: 
 a Mossbauer absorber atom; and    at least one of: 
 a chemical species capable of binding to DNA;  
 a massive particle of the group 
 polymers  
 colloids  
 macroaggregates, and  
 crystals; and  
 
 a site-selective molecule for a predetermined site within the body.  
   
     
     
         2 . The compound of  claim 1 , wherein said Mossbauer absorber atom comprises an atom from Table 7.  
     
     
         3 . The compound of  claim 1 , wherein said molecule comprises a molecule from Table 6.  
     
     
         4 . The compound of  claim 1  wherein the polymers are selected from the group consisting of proteins including: 
   57 Fe hemoglobin;  
   127 I thyroxine;  
   129 I thyroxine;  
   119 SN albumin;  
   121 Sb albumin;  
   125 Te albumin;  
   73 Ge albumin;  
   127 I albumin;  
   129 I albumin;  
   201 Hg albumin; and  
 organic and inorganic polymers of the size range of 5-50 nanometers.  
 
     
     
         5 . The compound of  claim 1 , wherein the polymers are selected from the group consisting of: 
 dibuty tin(119);    dimethylacrylate;    ruthenium(99);    bisbipyridine poly 4-vinyl pyridine;    poly[bisbipyridine osmium(189) bisvinylpyridine];      57 Fe polyvinyl ferrocene;    sulfonated polystyrene;    nafion;    ethylene diaminetetra acetate polymers;    organo silane-styrenesulfonate polymers;    lanthonide;    actinide; and    transition metals.    
     
     
         6 . The compound of  claim 1 , wherein colloids are selectedfrom the group consisting of: 
 a carboxyl;    a sulphate;    a phosphate;    a hydroxide;    a sulfide colloid; and    a gold colloid.    
     
     
         7 . The compound of  claim 1  wherein the macroaggregate is selected from one of the group consisting of: 
   57 Fe ferric hydroxide;  
   57 Fe ferric hydroxide including one of:  
 lanthanides  
 actinide or  
 transition metals.  
 
     
     
         8 . The compound of  claim 1  wherein the crystal is selected from one of the group consisting of: 
 water insoluble microprecipitates of the size range of 5 to 50 nanometers, including the Mossbauer absorber atom of:  
 127I − ;  
 129I − ;  
 AgI; and  
 silver halide precipitates.  
 
     
     
         9 . The compound of  claim 1  wherein the site selective molecule is selected from the group consisting of a monoclonal antibody, hematoporphyrin, porphyrin, hormone, and cationic lipophilic dye, and tat III protein.  
     
     
         10 . The compound of  claim 1  wherein said Mossbauer absorber atom is attached to said massive particles as one of an inclusion and an occlusion.  
     
     
         11 . The compound of  claim 1  wherein said compound is one of a weak acid and a weak base, and includes an additional proton.  
     
     
         12 . The compound of  claim 1 , wherein said molecule bond substantially eliminates translational energy modes in response to an influx of gamma rays.  
     
     
         13 . The compound of  claim 1  wherein said Mossbauer absorber atom bond substantially eliminates vibrational modes in response to an influx of gamma rays.  
     
     
         14 . The compound of  claim 1  wherein said Mossbauer absorber atom has a magnetic moment characteristic.  
     
     
         15 . The compound of  claim 14  wherein said Mossbauer absorber atom magnetic moment is responsive to an externally imposed magnetic field.  
     
     
         16 . The compound of  claim 15  wherein the interaction of said magnetic field causes selective alignment of the magnetic moment.  
     
     
         17 . The compound of  claim 16 , wherein said alignment of the magnetic moment provides selective absorption according to the polarization of the gamma rays.  
     
     
         18 . The compound of  claim 16  wherein the Mossbauer absorber atom has degenerate magnetic sublevels, and the interaction provides for the degeneracy of the energy of magnetic sublevels to be lifted.  
     
     
         19 . The compound of  claim 1  wherein said Mossbauer absorber atom undergoes internal conversion upon absorption of gamma rays, followed by an Auger cascade.  
     
     
         20 . The compound of  claim 1  wherein said Mossbauer absorber atom undergoes fluorescence upon absorption of gamma rays.  
     
     
         21 . The compound of  claim 1 , wherein said Mossbauer absorber atom has a resonant absorption energy and a resonant frequency in combinations with one of said atoms and said molecules bound thereto.  
     
     
         22 . The compound of  claim 13 , providing a change of resonance of said Mossbauer absorber atom according to one of an isomer shift, a magnetic hyperfine interaction, and a quadrapole hyperfine interaction.  
     
     
         23 . The compound of  claim 1 , wherein the Mossbauer absorber atom is bound to a biological target comprises one of intercalation, hydrogen bonding, electrostatic bonding, and covalent bonding.  
     
     
         24 . The compound of  claim 13 , wherein said biological target comprises a biological lattice.  
     
     
         25 . The compound of  claim 24 , wherein said biological lattice comprises a bone matrix.  
     
     
         26 . The compound of  claim 25  comprising one of  40 K,  153  Gd,  155  Gd,  157  Gd,  161  Dy,  163  Dy and  149 Sm.  
     
     
         27 . The compound of  claim 26 , wherein said massive particle comprises a massive inert carrier, in a recoil sense, of at least 10 8  daltons.  
     
     
         28 . A compound comprising: 
 antimony 121 sulfude colloid;      197  Au collidal gold;    carboxyl colloid;    sulphate colloid;    phosphate colloid;    hydroxide colloid;    sulfide colloid;    gelatin protected colloid;    dextran protected colloid;    micelles;    liposomes;    Te sulfur colloid;    chromic phosphate colloid;    yttrium hydroxide;    lantanide;    actinide.    
     
     
         29 . A pharmaceutical comprising: 
 an effective dosage of at least one of the compounds of claims  1  and  28 ; and    an acceptable form of a pharmaceutical carrier.    
     
     
         30 . The pharmaceutical of  claim 29 , wherein said pharmaceutical carrier comprises one of tragacarth, talc, agar-agar, lactose, polyglycols, ethanol, water, dextrose, saline and dimethylsulfoxide.  
     
     
         31 . The pharmaceutical of  claim 29  having the form of one of a tablet, liquid, gel, cream, ointment, spray, and lotion.  
     
     
         32 . A system for providing localized Mossbauer absorptions and selective release of energy in an organic medium, comprising: 
 a Mossbauer absorber atom selectively disposed within said organic medium;    a source of gamma ray energy selectively applied to said Mossbauer absorber atom, wherein said source and Mossbauer absorber atom have energy characteristics which differ in at least one of energy level, polarization and propagation direction relative to the nuclear moment of the Mossbauer absorber atom nuclei to which the gamma ray energy is to selectively applied; and    means for conforming the Mossbauer resonance characteristics of said source and said Mossbauer absorber atom, wherein Mossbauer absorption of the gamma rays from said source occurs in the Mossbauer absorber atom.    
     
     
         33 . The system of  claim 32  wherein said source comprises one of a magnetized ferromagnetic source, a quadrapole split source and a filtered source.  
     
     
         34 . The system of  claim 32  wherein said means for conforming comprises: 
 means for providing a gradient magnetic field of a selected flux gradient contour for selectively conforming the energy characteristics of the Mossbauer absorber atom to the incident energy at a selected location within said organic media.  
 
     
     
         35 . The system of  claim 34 , wherein said field gradient comprises field lines varying from substantially colinear with the incident energy from the source to field lines substantially perpendicular to said incident energy, wherein Mossbauer absorption in the Mossbauer absorber atom selectively occurs at a selected field line within the range of varying field lines which permits Mossbauer absorptions.  
     
     
         36 . The system of  claim 35 , wherein said means for conforming sequentially provides field lines of radial, transverse and radial orientation, respectively, in a plane parallel relative to said incident gamma rays, within said organic media.  
     
     
         37 . The system of  claim 36 , wherein said means for conforming includes a pair of Helmholtz coils having an axis aligned with an axis of the organic media, having a flow of current in one of said Helmholtz coil in opposition to the other of said Helmholtz coil.  
     
     
         38 . The system of  claim 36 , wherein said means for conforming includes: 
 a plurality of Helmholtz coils having a common axis aligned with an axis of the organic media and each having a flow of current in a common direction; and    a plurality of surface coils having axis perpendicular to the axis of said Helmholtz coils, wherein said surface coils include at least two coils having a current flow in mutual opposition.    
     
     
         39 . The system of  claim 32 , wherein said filtered source includes means for separating wanted from unwanted electromagnetic radiation.  
     
     
         40 . The system of  claim 35 , wherein said means for separating includes a crystaline diffraction grating.  
     
     
         41 . The system of  claim 32 , wherein said source of gamma rays comprises a tunable energy gamma ray source.  
     
     
         42 . The system of  claim 41 , wherein said source of gamma rays comprises a synchrotron source providing gamma rays of selected energy levels.  
     
     
         43 . The system of  claim 32 , wherein said means for conforming comprises means for providing acoustic energy to one of said organic media and said source.  
     
     
         44 . The system of  claim 43 , wherein said means for providing acoustic energy provides ultrasound energy.  
     
     
         45 . The system of  claim 43 , wherein said means for providing acoustic energy provides said acoustic energy along a path conincident with said applied gamma rays at a selected target location in said organic media.  
     
     
         46 . A process for providing spatially localized Mossbauer absorption in an organic medium, comprising the steps of: 
 selectively disposing a Mossbauer absorber atom within said organic media;    applying gamma rays to said Mossbauer absorber atom from a source, wherein said applied gamma rays and said Mossbauer absorber atom have energy characteristics which differ in at least one of energy level, polarization and propagation direction relative to the nuclear moment of the Mossbauer absorber atom nuclei to which the gamma ray energy is selectively applied;    conforming the Mossbauer resonance energy characteristic of said Mossbauer absorber atom and said applied gamma ray energy to provide Mossbauer absorption of the applied gamma rays by said selectively disposed Mossbauer absorber atom.    
     
     
         47 . The process of  claim 46 , wherein said step of applying comprises applying a gamma ray with a monochromatic line.  
     
     
         48 . The process of  claim 46 , wherein said step of conforming includes providing a gradient magnetic field of a selected flux gradient contour for selectively conforming the energy characteristics of the Mossbauer absorber atom to the applied gamma rays at a selected location within said organic media.  
     
     
         49 . The process of  claim 46 , wherein the step of conforming comprises the step of applying acoustic energy to one of said organic media and said source to cause a Mossbauer resonance energy of the Mossbauer absorber atom to coincide with the gamma ray energy at the selected location.  
     
     
         50 . The process of  claim 49 , wherein the step of applying an acoustic energy comprises applying ultrasound energy.  
     
     
         51 . A process for providing spatially localized energy absorption in an organic medium of a biological system, comprising the steps of: 
 administering a compound containing a Mossbauer absorber atom which is selectively uptaken to a selected location within said organic medium of said biological system;    applying gamma ray energy from a source to the location of selective uptake in said organic medium wherein said gamma ray energy conforms to the Mossbauer absorption line of the Mossbauer absorber atom at the selected locations, providing absorption of the gamma rays therein.    
     
     
         52 . The process of  claim 51  wherein the Mossbauer absorber atom comprise bone seeking Mossbauer absorber atoms, including one of  40 K, 153 Gd, 155 Gd, 157 Gd, 161 Dy, 163Dy and 149Sm.  
     
     
         53 . The process of  claim 51  wherein the step of administering a Mossbauer absorber atom comprises administering a compound containing a Mossbauer absorber atom.  
     
     
         54 . The process of  claim 51 , wherein the step of administering comprises the step of administering a compound containing a Mossbauer absorber atom having a selected molecule bound thereto.  
     
     
         55 . The process of  claim 54 , wherein said molecule comprises at least one of: 
 a monoclonal antibody, a hormone, a derivatizing functionality, a catonic lipophilic dye, a colloid, and an aggregate molecule.    
     
     
         56 . The process of  claim 55 , wherein said derivatizing functionality includes hematoporphryin and bleomycin.  
     
     
         57 . The process of  claim 54 , further including the step of binding one of the Mossbauer absorber atom and the molecule to a portion of the organic media at the selected location.  
     
     
         58 . The process of  claim 51 , wherein the Mossbauer resonance of said Mossbauer absorber atom differs from said applied gamma rays, the process further including the step of: 
 conforming the Mossbauer resonance characteristics energy of said Mossbauer absorber atom and said applied gamma rays to provide Mossbauer absorption of the applied gamma rays by said administered Mossbauer absorber atom.    
     
     
         59 . The process of  claim 58 , further including the step of interacting the Mossbauer absorber atom with the organic media at the selected locations to provide at least one of an isomer shift, magnetic hyperfine interaction and quadrapole interaction of the Mossbauer absorber atom nucleus.  
     
     
         60 . The process of  claim 58 , wherein the step of conforming comprises the step of applying a magnetic field having a selected field gradient contour for selectively conforming the energy characteristics of the Mossbauer absorber atom and the applied gamma rays, permitting gamma ray energy absorption by said mossbauer absorber atom.  
     
     
         61 . The process of  claim 58 , wherein the step of conforming comprises the step of applying acoustic energy to one of said organic media and said source to cause a Mossbauer resonance energy of the Mossbauer absorber atom to coincide with the gamma ray energy at the selected location.  
     
     
         62 . The process of  claim 61 , wherein the step of applying an acoustic energy comprises applying ultrasound energy.  
     
     
         63 . A process of providing energy absorption at a selected target tissue in a biological system,,comprising the steps of: 
 administering a Mossbauer absorber atom to said biological system wherein the uptake of the Mossbauer absorber atom in the target tissue provides a locally unique resonance energy of said Mossbauer absorber atom; and    applying gamma rays having an energy corresponding to said locally unique resonance of said Mossbauer absorber atom, permitting gama ray absorption therein.    
     
     
         64 . A method of using the compound of  claim 1  for medical diagnosis or treatment, comprising the steps of: 
 administering an effective amount of the compound to a biological system; and  
 selectively applying a selected frequency electromagnetic radiation to the biological system to provide Mossbauer absorption of said electromagnetic radiation at selected target areas within said biological system.  
 
     
     
         65 . The method of  claim 64  wherein said electromagnetic radiation comprises gamma rays.  
     
     
         66 . The method of  claim 64 , wherein said step of administering comprises at least one of intravenous, intramuscular, subcutaneous, intra-arterial and intra-articular injection of said compound.  
     
     
         67 . The method of  claim 64 , wherein said step of administering comprises at least one of topical application and oral administration.  
     
     
         68 . The method of  claim 64 , wherein said step of selectively applying comprises employing electromagnetic radiation at a dose effective to eliminate cell lines causing selective necrosis at said target areas.  
     
     
         69 . The method of  claim 64 , wherein said biological system comprises an animal; 
 said target area comprises a cancer; and    said Mossbauer absorption by said compound causes cancer necrosis.    
     
     
         70 . The method of  claim 69 , wherein said animal comprises a human.