Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Reexamination Certificate
1995-05-30
2001-05-01
Dudash, Diana (Department: 1619)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
C534S010000, C534S011000, C534S015000, C600S001000, C600S002000, C600S003000
Reexamination Certificate
active
06224848
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to pharmaceuticals and apparatus to implement the Mossbauer effect for diagnostic and therapeutic purposes.
BACKGROUND OF THE INVENTION
In the treatment of tumors by ionizing radiation, typically X-rays or gamma rays are used. The ideal in radiation therapy of malignant disease is achieved when the tumor is completely eradicated, and the surrounding normal tissue, in the treated volume, shows little or no evidence of structural or functional injury. The important factor in successful treatment is the difference in radiosensitivity of neoplastic and normal cells. All tissues, normal and neoplastic, are affected by radiation so that radiosensitivity is a relative term. The basic consideration of radiation therapy is that cells that are actively proliferating or that cells which are of a primitive type are more sensitive than normal tissue so that there is usually a considerable margin between doses that are damaging to neoplastic and to normal cells. If this is the case, then a multifraction dose schedule decreases the size of the tumor over time while permitting time between doses for normal tissue to recover. A constant fraction of tumor cells are killed with each treatment, and theoretically the tumor can be completely eliminated with a sufficient number of treatments. However, normal tissue has a memory of its accumulated radiation dose such that a threshold to the total dose acquired over the patient's history is eventually reached. Exceeding this threshold results in unacceptable side effects. Thus, the tumor volume must be reduced sufficiently before the threshold is reached or the cancer is incurable by this modality of therapy.
SUMMARY OF THE INVENTION
The present invention is pharmaceuticals, apparatus, and a process which provides diagnosis, therapy and other biological effects by use of highly selective absorption of radiation called the Mossbauer effect. Mossbauer absorption which is exploited for diagnosis and therapy by the present invention is completely analogous to optical absorption. For purposes of the present application, Mossbauer resonance is synonymously defined as an energy and a frequency which are interchangeable by the relationship:
E=hv=hc/&lgr; (1)
For optical absorption, the ultimate source of radiation consists of excited atoms or molecules which decay to the ground state. The radiation, after being suitably monochromatized by a prism or diffraction grating, is incident upon the sample, and the intensity of the beam which is transmitted through the sample (absorber) varies as a function of the frequency as the photons of energy equivalent to electronic, vibrational, rotational, and translational transitions are absorbed. In Mossbauer absorption, the source comprises excited nuclei in appropriate highly bonding surroundings. The nuclei, in decaying to their ground state, emit gamma radiation that is highly monochromatic. In fact, the gamma ray line can be so narrow that its frequency may be shifted significantly by incorporating the source or absorber in a mass driver oscillating at moderate velocities to produce a Doppler effect. The velocity of the mass driver which provides a Doppler shift to the gamma ray photons functions analogously to the dispersion device in optical absorption. By varying the driving velocity, a resonance system can be driven by the emitted gamma photons with regard to the nuclear energy transitions of the sample (absorber).
As part of the present invention, useful application of the Mossbauer effect in living tissue is provided by an administered pharmaceutical containing a Mossbauer isotope as the absorber. The pharmaceutical is resonantly excited by the gamma photons provided by this apparatus where the gamma ray energy, polarization and propagation direction are resonant with the nuclear transitions of the isotope in the target tissue, from which the surrounding nontarget tissue differs significantly in resonance conditions to achieve an enhanced therapeutic or diagnostic function and minimum effects in the nontarget tissue.
As a further aspect of the present invention the resonant (Mossbauer) absorption of gamma rays by nuclei of the administered isotopes at the target tissue, provides a specific, lethal release of energy to a susceptible biological target such as the DNA of the target tissue as part of a therapeutic process. Alternatively, the present invention provides diagrams by monitoring the release of nonlethal energy, as described in detail, below. An acronym for Mossbauer Isotopic Resonant Absorption of Gamma Emission, hereafter, MIRAGE, is created, and the corresponding therapy and pharmaceuticals are disclosed as MIRAGE therapy and MIRAGE pharmaceuticals.
The MIRAGE pharmaceuticals contain Mossbauer absorber isotopes and bind to a target tissue to become immobilized, permitting Mossbauer nuclear resonant absorption of gamma radiation in the vicinity of the target tissue. The excitation is by a radiation source, the apparatus of the invention, at the corresponding resonant Mossbauer absorption frequency of selected tissue having received the administered pharmaceutical where excitation effects nuclear transitions to cause selective energy absorption in the selected target tissue. For diagnostic purposes, de-excitation fluorescence of the isotope is monitored with gamma ray scanning equipment. For therapeutic purposes, the energy is converted into particle radiation by the Mossbauer isotope at the target tissue by internal conversion followed by an Auger cascade which results in damage to a susceptible biological target such as radiolysis of DNA resulting in lethal double strand breaks in the DNA molecules of the target tissue.
Tissue selectivity is achieved by causing the Mossbauer effect to occur to a greater extent in the selected target tissue than the nontarget tissue. One aspect of the present invention providing selectivity is by administering pharmaceuticals which are selectively taken up by the selected tissue. Alternate embodiments of the present invention selectively control Mossbauer resonant absorption by control of the conditions for resonance of gamma ray energy, polarization, and propagation direction, wherein pharmaceuticals when in the vicinity of selected versus nonselected tissue, have a differential of one or more such conditions. Such conditions are made different by magnetic fields or ultrasonic power which are applied, effecting an absorption differential for selected versus nonselected tissue. Mossbauer absorption at the target tissue is provided by shifting the source frequency to conform to that of the MIRAGE isotope in the vicinity of the target tissue. Alternately the absorption characteristics of the MIRAGE isotope is controlled to match the imparted radiation at the site of the target tissue.
Apparatus providing the selectively shifted radiation comprises a Mossbauer source supported by a mass drive or ultrasonic transducer drive which can suitably “tune” the emitted radiation to the proper Mossbauer absorption frequency by imparting a Doppler frequency shift or by shifting the energy of emission side bands, respectively. In addition, the apparatus includes means to polarize the emission and possesses means to produce external magnetic fields and an ultrasonic beam to effect selective absorption by changing the gamma ray energy and/or polarization and propagation direction conditions to achieve resonance in the absorber pharmaceutical selectively.
In addition, the present invention includes apparatus to separately and controllably polarize both the emission radiation and the absorber pharmaceutical at the target tissue to achieve the desired controlled absorption. Alternate embodiments of the apparatus according to the present invention provide selectively controlled external magnetic fields at the target tissue to effect selective absorption by changing the gamma ray energy and/or polarization and propagation direction conditions to achieve resonance in the MIRAGE absorber pharmaceutical. The App
DeConti Giulio A.
Dudash Diana
Hartley Michael G.
Lahive & Cockfield LLP
Triano, III Nicholas P.
LandOfFree
Pharmaceuticals providing diagnosis and selective tissue... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceuticals providing diagnosis and selective tissue..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceuticals providing diagnosis and selective tissue... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2563771