US4500507A
Expired / Lapsed
US
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Diagnostic composition for radiologic imaging of neoplasms in the body and method of preparation
Assignee: Individual
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Filing: 1981-10-30
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Granted: 1985-02-19
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Expires: 2001-10-30
Abstract
Abstract A novel chemical method of labeling porphyrin compounds, specifically hematoporphyrin derivative (HPD), with the radionuclide Technetium-99m producing a radioactive tracer material suitable for biomedical applications. HPD labeled with 99m Tc is biologically active in vivo and is preferentially taken up by neoplastic tissues. This provides a simple and specific means of visualizing tumors in man or animal by scintigraphic imaging techniques.
Inventors
- 👤 Dennis W. Wong
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 14:42
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/02; A61K51/04; A61K51/0474; A61K51/0485; A61K2123/00
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
110 words
A method of labeling porphyrin compounds, related analogs, derivatives and substances containing porphyrin with the radionuclides of Technetium(Tc) at physiologic pH 7-8 condition which comprises the sequential steps of: a. treating the radionuclide of technetium with a reducing agent at room temperature for 1-10 minutes; b. raising the pH of the acidic mixture of step (a) to 7.4 with a sufficient amount of alkaline citrate complexing reagent; c. binding of the radionuclide of technetium to the porphyrin ligand by adding 1-10 ml of an aqueous solution of the porphyrin compound desired to be labeled to the admixture of step (b) and incubating the admixture at room temperature for 30 minutes.
Claim 2
Independent Claim
110 words
A method of labeling porphyrin compounds, related analogs, derivatives and substances containing porphyrin with the radionuclides of Technetium(Tc) at physiologic pH 7-8 condition which comprises the sequential steps of: a. treating the radionuclide of technetium with a reducing agent at room temperature for 1-10 minutes; b. raising the pH of the acidic mixture of step (a) to 7.4 with a sufficient amount of alkaline citrate complexing reagent; c. binding of the radionuclide of technetium to the porphyrin ligand by adding 1-10 ml of an aqueous solution of the porphyrin compound desired to be labeled to the admixture of step (b) and incubating the admixture at room temperature for 30 minutes.
Claim 3
Dependent Claim
24 words
A method according to claim 1, wherein said radionuclides of technetium is selected from the group consisting 99m Tc, 95m Tc and 99 Tc.
Claim 4
Dependent Claim
30 words
A method according to claim 2, wherein said radionuclide of technetium is an aqueous solution of sodium pertechnetate in normal saline providing from 1 mCi to 5000 mCi of radioactivity.
Claim 5
Dependent Claim
25 words
A method according to claim 1, wherein said reducing agent is stannous ions selected from the group consisting stannous chloride, stannous fluoride or stannous tartrate.
Claim 6
Dependent Claim
24 words
A method according to claim 4, wherein said stannous reducing agent is present in the amount of 0.1-10 mg dissolved in 0.05-0.1N hydrochloric acid(HCl).
Claim 7
Dependent Claim
24 words
A method according to claim 5, wherein said stannous reducing agent is present in the amount of 0.2-5 mg per ml of 0.05N HCl.
Claim 8
Dependent Claim
30 words
A method according to claim 1, wherein said alkaline citrate complexing reagent is an aqueous solution of 0.5-10% sodium citrate made alkaline to pH above 8 with 1N NaOH solution.
Claim 9
Dependent Claim
25 words
A method according to claim 7, wherein said alkaline citrate complexing reagent is an aqueous solution of 2% sodium citrate having a pH of 12.4.
Claim 10
Dependent Claim
23 words
A method according to claim 1, wherein said porphyrin compound is selected from the group consisting coproporphyrins, protoporphyrins, uroporphyrins, hematoporphyrin and hematoporphyrin derivative(HPD).
Claim 11
Dependent Claim
22 words
A method according to claim 9, wherein said porphyrin compound is dissolved in an aqueous medium having a pH of above 7.
Claim 12
Dependent Claim
36 words
A method according to claim 10, wherein said porphyrin compound is present in the amount of 0.1-1000 mg dissolved in distilled water or normal saline adjusted to a pH of 7-8 with 0.1 to 1N NaOH.
Claim 13
Dependent Claim
32 words
A method according to claim 11, wherein said porphyrin compound is present in the amount of 5-100 mg dissolved in pH 7.4 normal saline together with any pharmaceutically acceptable preservative or stabilizer.
Claim 14
Independent Claim
119 words
A method of labeling hematoporphyrin derivative(HPD) with 99m Tc at physiologic pH 7-8 condition producing a diagnostic composition suitable for radiologic imaging of neoplasms in man or in animal comprising the sequential steps of: a. treating 2-3 ml(60-200 mCi) of 99m Tc-pertechnetate in normal saline with 0.5 ml of a solution of 0.1-5 mg stannous chloride, stannous fluoride or stannous tartrate in 0.05N HCl solution at room temperature for 10 minutes; b. raising the pH of the acidic mixture of step (a) to 7.4 with a sufficient amount of the pH 12.4 sodium citrate/NaOH solution; c. adding 0.5-1 ml(5-10 mg) HPD solution to the neutralized mixture of step (b) and incubating the admixture at room temperature for 10-30 minutes.
Claim 15
Independent Claim
119 words
A method of labeling hematoporphyrin derivative(HPD) with 99m Tc at physiologic pH 7-8 condition producing a diagnostic composition suitable for radiologic imaging of neoplasms in man or in animal comprising the sequential steps of: a. treating 2-3 ml(60-200 mCi) of 99m Tc-pertechnetate in normal saline with 0.5 ml of a solution of 0.1-5 mg stannous chloride, stannous fluoride or stannous tartrate in 0.05N HCl solution at room temperature for 10 minutes; b. raising the pH of the acidic mixture of step (a) to 7.4 with a sufficient amount of the pH 12.4 sodium citrate/NaOH solution; c. adding 0.5-1 ml(5-10 mg) HPD solution to the neutralized mixture of step (b) and incubating the admixture at room temperature for 10-30 minutes.
Claim 16
Dependent Claim
22 words
Hematoporphyrin derivative(HPD) a compound selected from the group of porphyrins is labeled with 99m Tc according to the method of claim 13.
Claim 17
Dependent Claim
73 words
A method of localizing and detecting neoplasms in man or in animal by scintigraphic imaging procedures comprising; a. administering intravenously to said mammal 0.1-50 mCi of 99m Tc-HPD labeled according to the method of claim 13; b. scanning said mammal with a conventional scintillation Anger camera or a rectilinear scanner at various times intervals from 0.5-24 hours; c. observing increasing radioactivity accumulated at the sites of these tumors as seen in the scintigrams.
Claim 18
Dependent Claim
77 words
A kit for labeling porphyrin compounds, related analogs, derivatives and substances containing porphyrin with the radionuclides of technetium at physiologic pH 7-8 condition comprising a stannous reducing agent, an alkaline citrate complexing reagent and an aqueous solution of a porphyrin compound desired to be labeled with the radionuclide aseptically prepared and packaged separately in sealed, sterile, apyrogenic containers wherein said kit is used with a solution of 99m Tc-, 95m Tc- or 99 Tc-pertechnetate in normal saline.
Claim 19
Dependent Claim
77 words
A kit for labeling porphyrin compounds, related analogs, derivatives and substances containing porphyrin with the radionuclides of technetium at physiologic pH 7-8 condition comprising a stannous reducing agent, an alkaline citrate complexing reagent and an aqueous solution of a porphyrin compound desired to be labeled with the radionuclide aseptically prepared and packaged separately in sealed, sterile, apyrogenic containers wherein said kit is used with a solution of 99m Tc-, 95m Tc- or 99 Tc-pertechnetate in normal saline.
Claim 20
Dependent Claim
26 words
A kit according to claim 16, wherein said stannous reducing agent is stannous ions selected from the group consisting stannous chloride, stannous fluoride or stannous tartrate.
Claim 21
Dependent Claim
22 words
A kit according to claim 17, wherein stannous reducing agent is dissolved in 0.05-0.1N HCl solution in a concentration of 0.1-5 mg/ml.
Claim 22
Dependent Claim
35 words
A kit according to claim 18, wherein said stannous reducing agent is present in the amount of 0.2-5 mg per ml of 0.05N HCl solution and is packaged in the form of a freeze-dried solid.
Claim 23
Dependent Claim
30 words
A kit according to claim 16, wherein said alkaline citrate complexing reagent is an aqueous solution of 0.5-10% sodium citrate made alkaline to a pH above 8 with 1N NaOH.
Claim 24
Dependent Claim
35 words
A kit according to claim 20, wherein 1-5 ml of an aqueous solution of 2% sodium citrate at pH 12.4 is packaged in the form of a freeze-dried solid as said alkaline citrate complexing reagent.
Claim 25
Dependent Claim
23 words
A kit according to claim 16, wherein said porphyrin compound is selected from the group consisting coproporphyrins, protoporphyrins, uroporphyrins, hematoporphyrin and hematoporphyrin derivative(HPD).
Claim 26
Dependent Claim
28 words
A kit according to claim 22, wherein said porphyrin compound is HPD dissolved in an aqueous medium in the concentration of 1-100 mg/ml having a pH of 7-8.
Claim 27
Dependent Claim
33 words
A kit according to claim 23, wherein said HPD is present in the amount of 5-10 mg dissolved in 1-2 ml pH 7.4 normal saline together with any pharmaceutically acceptable preservative or stabilizer.
Claim 28
Dependent Claim
137 words
A method of preparing 99m Tc-labeled HPD injection at physiologic pH 7-8 condition using the sterile labeling reagent kit of claim 16 with a solution of 99m Tc-pertechnetate in normal saline producing a pharmaceutical composition suitable for radiologic imaging of neoplasms in man or in animal which comprises the sequential steps of: a. reconstituting the alkaline citrate complexing reagent with 1-5 ml of Water for Injection until completely dissolved; b. treating the freeze-dried stannous reducing agent with 2-3 ml (60-200 mCi) 99m Tc-pertechnetate in normal saline for about 1-10 minutes; c. raising the pH of the mixture of step (b) to 7.4 with 0.5-1 ml of the reconstituted alkaline citrate complexing reagent; d. adding to the neutralized admixture of step (c) 1 ml of the HPD solution and incubating the admixture at room temperature for 10-30 minutes.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-02-19 | 1988-08-20 | 1989-02-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-02-19 | 1992-08-20 | 1993-02-19 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-02-19 | 1996-08-20 | 1997-02-19 | $7700.00 | Window Closed / Lapsed |