Method of using metaloporphyrins for treatment of arteriosclerotic lesions

• US 20030235531A1
• Filed: 08/08/2002
• Published: 12/25/2003
• Est. Priority Date: 06/21/2002
• Status: Active Grant

• Current Assignee: Edwin L. Adair
• Original Assignee: Edwin L. Adair
• Inventors: Adair, Edwin L.
• Granted Patent: US 6,753,160 B2
• Time in Patent Office: Days
• US Class Current: 424/1.11
• CPC Class Codes: A61B 6/12 Arrangements for detecting or locating foreign bodies
• CPC Class Codes: A61K 49/0036 Porphyrins used in photodynamic therapy A61K41/0071 or A61K41/0076; used as targeting group or modifying agent for targeting a therapeutic compound A61K47/546
• CPC Class Codes: A61K 51/0485 Porphyrins, texaphyrins wherein the nitrogen atoms forming the central ring system complex the radioactive metal
• CPC Class Codes: A61N 2005/1061 using an x-ray imaging system having a separate imaging source
• CPC Class Codes: A61N 5/1049 for verifying the position of the patient with respect to the radiation beam
• CPC Class Codes: A61N 5/1067 in real time, i.e. during treatment
• CPC Class Codes: G01N 33/5091 for testing the pathological state of an organism
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: H04N 23/54 Mounting of pick-up tubes, electronic image sensors, deviation or focusing coils
• CPC Class Codes: H04N 23/555 for picking-up images in sites, inaccessible due to their dimensions or hazardous conditions, e.g. endoscopes or borescopes
• CPC Class Codes: Y10S 435/968 High energy substrates, e.g. fluorescent, chemiluminescent, radioactive

Abstract

A method for diagnosis and treatment of arteriosclerotic lesions is provided wherein the method is characterized by introducing a chemical compound to the patient, the compound being a complex of a photosensitive portion, and a radioactive portion. Cells which exhibit an affinity for the porphyrin element indicate sites of plaque buildup. The radioactive portion within the compound allows tomographic scanning as well as simultaneous radiation treatment. The complexed compound can be introduced to the patient a desired number of times to provide the necessary radiation treatment and ongoing monitoring of plaque removal. Further observation or treatment may be conducted through a fluorescence guided endoscopic procedure.

Claims

1. A method of screening and treatment of arteriosclerotic disease, said method comprising the steps of:

introducing a complexed compound to a patient for cell uptake of the compound, the compound comprising a first portion which includes a photosensitive component, and a second portion comprising a radioactive marker;

conducting tomographic scanning of the patient to determine whether targeted cells in the patient have demonstrated an affinity for the photosensitive compound thereby indicating the presence of plaque buildup; and

conducting radiation therapy by the second portion of the compound which results in selective ionizing radiation exposure.

2. A method, as claimed in claim 1, wherein:

said first portion of said compound is selected from the group consisting of 5-ALA, protoporphyrin IX, TCPP, hematoporphyrin derivative, photofrin, uroporphyrin, coproporphyrin, TPPS, and TMPP; and

said second portion of said compound is selected from the group consisting of radioisotopes of copper which may be complexed with said first portion.

3. A method, as claimed in claim 1, wherein said radioisotope of copper is ⁶⁷Cu.

4. A method, as claimed in claim 1, further comprising the step of:

selecting the type of radioactive marker to match a type of radiation treatment best suited for treatment of a disease.

5. A method, as claimed in claim 1, further comprising the step of:

introducing the complexed compound again to the patient to achieve further radiation therapy; and

conducting tomographic scanning to view treatment results.

6. A method, as claimed in claim 1, further comprising the step of:

introducing the complexed compound wherein the second portion is selectively dosed to deliver a desired amount of radiation.

7. A method, as claimed in claim 6, further including the step of adjusting the type and dosage of the second portion to provide effective therapy.

8. A radiopharmaceutical composition for the visualization, diagnosis or treatment of arteriosclerosis comprising a porphyrin complexing a radiation-emitting metal and a pharmaceutical excipient.

9. The radiopharmaceutical composition of claim 8, wherein the porphyrin is selected from the group consisting of Protoporphyrin IX and derivatives thereof;

Porphine;

Octaethylporphine;

Hematoporphyrin IX and derivatives thereof;

Etioporphyrin;

Etioporphyrin I;

meso-Tetraphenylporphine and derivatives thereof;

Coproporphyrin I;

Coproporphyrin III;

Deuteroporphyrin IX;

Mesoporphyrin IX;

Tetra Tosylate;

Uroporphyrin I; and

Iso-hematoporphyrin IX.

10. The radiopharmaceutical composition of claim 8, wherein the radiation-emitting metal is a radioactive isotope of a metal selected from the group consisting of silver, aluminum, cadmium, cobalt, chromium, copper, iron, gadolinium, indium, lutetium, magnesium, manganese, nickel, palladium, platinum, rhodium, ruthenium, scandium, silicon, tin, titanium oxide, vanadium oxide, ytterbium and zinc.

11. A method of visualizing an arteriosclerotic region in an individual comprising:

(a) administering a radiopharmaceutical comprising a porphyrin complexing a gamma radiation-emitting metal to an individual, and

(b) detecting the gamma radiation emitted from within the individual to create an image of an arteriosclerotic region within the individual.

12. The method of claim 11, wherein the porphyrin is selected from the group consisting of Protoporphyrin IX and derivatives thereof;

Porphine;

Octaethylporphine;

Hematoporphyrin IX and derivatives thereof;

Etioporphyrin;

Etioporphyrin I;

meso-Tetraphenylporphine and derivatives thereof;

Coproporphyrin I;

Coproporphyrin III;

Deuteroporphyrin IX;

Mesoporphyrin IX;

Tetra Tosylate;

Uroporphyrin I; and

Iso-hematoporphyrin IX.

13. The method of claim 11, wherein the radiation-emitting metal is a radioactive isotope of a metal selected from the group consisting of silver, aluminum, cadmium, cobalt, chromium, copper, iron, gadolinium, indium, lutetium, magnesium, manganese, nickel, palladium, platinum, rhodium, ruthenium, scandium, silicon, tin, titanium oxide, vanadium oxide, ytterbium and zinc.

14. The method of claim 11, wherein the detecting step comprises positron emission tomography (PET) scanning.

15. The method of claim 11, wherein the detecting step comprises single photon emission computed tomography (SPECT) scanning.

16. A method of diagnosing arteriosclerosis in an individual comprising:

(a) administering a radiopharmaceutical comprising a porphyrin complexing a gamma radiation-emitting metal to an individual,

(b) detecting the gamma radiation emitted from within the individual, and

(c) comparing the detected gamma radiation reading from the individual with reference readings wherein comparison to reference readings is indicative of the presence of arteriosclerosis in an individual.

17. The method of claim 16, wherein the detecting step is selected from the group consisting of PET scanning and SPECT scanning, and wherein the reference readings are PET or SPECT scans of individuals known to have arteriosclerosis.

18. The method of claim 16, wherein the detecting step is selected from the group consisting of PET scanning and SPECT scanning, and wherein the reference readings are PET or SPECT scans of individuals in which arteriosclerosis is absent.

19. The method of claim 16, wherein the porphyrin is selected from the group consisting of Protoporphyrin IX and derivatives thereof;

Porphine;

Octaethylporphine;

Hematoporphyrin IX and derivatives thereof;

Etioporphyrin;

Etioporphyrin I;

meso-Tetraphenylporphine and derivatives thereof;

Coproporphyrin I;

Coproporphyrin III;

Deuteroporphyrin IX;

Mesoporphyrin IX;

Tetra Tosylate;

Uroporphyrin I; and

Iso-hematoporphyrin IX.

20. The method of claim 16, wherein the gamma radiation-emitting metal is a radioactive isotope of a metal selected from the group consisting of silver, aluminum, cadmium, cobalt, chromium, copper, iron, gadolinium, indium, lutetium, magnesium, manganese, nickel, palladium, platinum, rhodium, ruthenium, scandium, silicon, tin, titanium oxide, vanadium oxide, ytterbium and zinc.

21. A method of treating arteriosclerosis in an individual comprising administering a radiopharmaceutical comprising a porphyrin complexing a radiation-emitting metal to an individual.

22. The method of claim 21, wherein the radiation-emitting metal is a beta radiation-emitting metal.

23. The method of claim 21, wherein the radiation-emitting metal is a gamma radiation-emitting metal.

24. The method of claim 21, wherein the porphyrin is selected from the group consisting of Protoporphyrin IX and derivatives thereof;

Porphine;

Octaethylporphine;

Hematoporphyrin IX and derivatives thereof;

Etioporphyrin;

Etioporphyrin I;

meso-Tetraphenylporphine and derivatives thereof;

Coproporphyrin I;

Coproporphyrin III;

Deuteroporphyrin IX;

Mesoporphyrin IX;

Tetra Tosylate;

Uroporphyrin I; and

Iso-hematoporphyrin IX.

25. The method of claim 21, wherein the radiation-emitting metal is a radioactive isotope of a metal selected from the group consisting of silver, aluminum, cadmium, cobalt, chromium, copper, iron, gadolinium, indium, lutetium, magnesium, manganese, nickel, palladium, platinum, rhodium, ruthenium, scandium, silicon, tin, titanium oxide, vanadium oxide, ytterbium and zinc.