WO1999058149B1 - Controlled activation of targeted radionuclides - Google Patents

Controlled activation of targeted radionuclides

Info

Publication number
WO1999058149B1
WO1999058149B1 PCT/US1999/009584 US9909584W WO1999058149B1 WO 1999058149 B1 WO1999058149 B1 WO 1999058149B1 US 9909584 W US9909584 W US 9909584W WO 1999058149 B1 WO1999058149 B1 WO 1999058149B1
Authority
WO
Grant status
Application
Patent type
Prior art keywords
radionuclide
shell
tissue
abnormal
radiation
Prior art date
Application number
PCT/US1999/009584
Other languages
French (fr)
Other versions
WO1999058149A1 (en )
Inventor
James C Chen
Original Assignee
Light Sciences Lp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K51/00Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1262Capsules
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation; Therapies using these preparations
    • A61K41/0028Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation; Therapies using these preparations
    • A61K41/0042Photocleavage of drugs in vivo, e.g. cleavage of photolabile linkers in vivo by UV radiation for releasing the pharmacologically-active agent from the administered agent; photothrombosis or photoocclusion

Abstract

Abnormal tissue or malignant organelles within such tissue are destroyed by alpha particles emitted by radionuclide cores that are linked to the abnormal tissue. Targeted radionuclide beads each includes an alpha emitter radionuclide core (12) to which a plurality of antibody linking sites (14) are coupled. Surrounding the linking sites and radionuclide core is a polymeric shell (16) that absorbs alpha particles emitted by the core. A reagent (18) is applied to or included within the polymeric shell. Depending upon the material used for the reagent, it is activated by light of a particular waveband that is selectively applied after antibody linking sites (20) on the exterior of the shell have linked the targeted radionuclide to abnormal tissue in the body of a patient. Certain reagents are activated by light in a waveband corresponding to an absorption waveband of the reagent, while other types of reagents are activated by ultrasonic energy applied from an ultrasound source. When thus activated, the reagent causes fragmentation of the polymeric shell, enabling the alpha particles to pass into the abnormal tissue to which the radionuclide core becomes linked. The alpha particles destroy the abnormal tissue. It is also contemplated that the radionuclide core may instead emit beta particles, which though less toxic than alpha particles, can still destroy the targeted abnormal tissue.

Claims

-16- AMENDED CLAIMS
[received by the International Bureau on 20 December 1999 (20.12.99); new claims 38 and 39 added; remaining claims unchanged (2 pages)]
28. The method of Claim 27, wherein the binding agent comprises an antibody.
29. The method of Claim 26, further comprising the step of applying a binding agent to the radionuclide before the radionuclide is enclosed within the shell, said binding agent preferentially targeting and linking to the abnormal tissue at the treatment site, rather than to normal tissue.
30. The method of Claim 29, wherein the binding agent comprises an antibody.
31. The method of Claim 26, wherein the reagent is activated by one of an ultrasonic signal and a light signal.
32. The method of Claim 26, wherein the reagent comprises one of a Methylene Blue and a Bengal Rose photoreactive agent.
33. The method of Claim 26, wherein the shell comprises a polymer.
34. The method of Claim 33, wherein the shell comprises lignan.
35. The method of Claim 26, wherein the radionuclide enclosed within the shell is administered to the patient within a vascular passage and conveyed to the treatment site within a vascular fluid.
36. The method of Claim 26, wherein radionuclides enclosed within a shell in which the reagent is not activated and not retained at the treatment site are naturally excreted from the patient's body.
37. The method of Claim 26, wherein the radiation emitted by the radionuclide comprises alpha particles and the radionuclide has a half life that is substantially less than a time required for the shell to degrade within the patient's body.
38. A method for destroying abnormal tissue within a patient's body, comprising the steps of:
(a) providing a radionuclide that emits radiation having a lethal effect on the abnormal tissue;
(b) enclosing the radionuclide within a shell that blocks the radiation emitted by the radionuclide, said shell comprising a generally non-active material, and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell; -17-
(c) applying a binding agent to the shell, producing a targeted radionuclide, said binding agent being selected so that the shell preferentially links to the abnormal tissue, but not to normal tissue;
(d) administering the targeted radionuclide to a patient, said binding agent selectively linking the shell enclosing the radionuclide to the abnormal tissue; and
(e) activating the selectively activatable reagent, causing the shell to be breached, thereby enabling said radionuclide to emit the radiation, to destroy the abnormal tissue.
39. A therapeutic construct for use in destroying abnormal tissue within a patient's body, comprising:
(a) a radionuclide substance that emits radiation having a lethal effect on abnormal tissue;
(b) a shell that blocks the radiation emitted by the radionuclide, said shell enclosing the radionuclide and comprising a generally non-active material and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell; and
(c) a binding agent disposed on a surface of the shell, said binding agent being selected to preferentially link to the abnormal tissue, but not to normal tissue, said shell, said radionuclide, and said binding agent together comprising a targeted radionuclide that is adapted to be administered to a patient, bind to the abnormal tissue in the patient's body, and when the reagent is activated, expose the abnormal tissue to the radiation emitted by the radionuclide, destroying the abnormal tissue.
-18-
STATEMENT UNDER ARTICLE 19
Applicant acknowledges receipt of the International Search Report mailed 26 October 1999 and requests that the above-identified international application be amended in accordance with the attached replacement sheets. Replacement sheets 15 and 15A, containing the amendments shown below, should be substituted for original sheet 15. Applicant requests that the attached replacement sheets be published with the application.
Two claims (38 and 39) have been added to the application in the amendment shown below. New Claims 38 and 39 recite a shell comprising a generally inactive material and a selectively activatable reagent that when activated, cause the shell to be breached. These claims are fully supported by both the drawing figures (see FIGURES 1 and 4) and the specification (see page 5, line 20 to page 6, line 15). None of the prior art either teaches or suggests such a shell for encapsulating a radionuclide. Accordingly, new Claims 38 and 39, which are enabled by the specification, recite a novel and nonobvious invention. /// /// /// -19-
In the Claims:
Please add new Claims 38 and 39 as follows.
—38. A method for destroying abnormal tissue within a patient's body, comprising the steps of:
(a) providing a radionuclide that emits radiation having a lethal effect on the abnormal tissue;
(b) enclosing the radionuclide within a shell that blocks the radiation emitted by the radionuclide, said shell comprising a generally non-active material, and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell;
(c) applying a binding agent to the shell, producing a targeted radionuclide, said binding agent being selected so that the shell preferentially links to the abnormal tissue, but not to normal tissue;
(d) administering the targeted radionuclide to a patient, said binding agent selectively linking the shell enclosing the radionuclide to the abnormal tissue; and
(e) activating the selectively activatable reagent, causing the shell to be breached, thereby enabling said radionuclide to emit the radiation, to destroy the abnormal tissue.
39. A therapeutic construct for use in destroying abnormal tissue within a patient's body, comprising:
(a) a radionuclide substance that emits radiation having a lethal effect on abnormal tissue;
(b) a shell that blocks the radiation emitted by the radionuclide, said shell enclosing the radionuclide and comprising a generally non-active material and a selectively activatable reagent that when activated, is adapted to cause the shell to be breached, enabling the radiation emitted by the radionuclide to pass without blockage by the shell; and
(c) a binding agent disposed on a surface of the shell, said binding agent being selected to preferentially link to the abnormal tissue, but not to normal tissue, said shell, said radionuclide, -20-
and said binding agent together comprising a targeted radionuclide that is adapted to be administered to a patient, bind to the abnormal tissue in the patient's body, and when the reagent is activated, expose the abnormal tissue to the radiation emitted by the radionuclide, destroying the abnormal tissue.—
PCT/US1999/009584 1998-05-13 1999-04-30 Controlled activation of targeted radionuclides WO1999058149B1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US7832998 true 1998-05-13 1998-05-13
US09/078,329 1998-05-13

Publications (2)

Publication Number Publication Date
WO1999058149A1 true WO1999058149A1 (en) 1999-11-18
WO1999058149B1 true true WO1999058149B1 (en) 2000-02-03

Family

ID=22143333

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/009584 WO1999058149B1 (en) 1998-05-13 1999-04-30 Controlled activation of targeted radionuclides

Country Status (1)

Country Link
WO (1) WO1999058149B1 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6454789B1 (en) 1999-01-15 2002-09-24 Light Science Corporation Patient portable device for photodynamic therapy
US6602274B1 (en) 1999-01-15 2003-08-05 Light Sciences Corporation Targeted transcutaneous cancer therapy
CA2490692A1 (en) 2002-06-27 2004-01-08 Health Research, Inc. Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1338736C (en) * 1986-12-05 1996-11-26 Roger Baurain Microcrystals containing an active ingredient with affinity for phospholipids and at least one phospholipid; process for preparing the same
US5283255A (en) * 1987-01-20 1994-02-01 The University Of British Columbia Wavelength-specific cytotoxic agents
US5733572A (en) * 1989-12-22 1998-03-31 Imarx Pharmaceutical Corp. Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles
US5580575A (en) * 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
DE69433723T3 (en) * 1993-02-22 2008-10-30 Abraxis Bioscience, Inc., Los Angeles A method for the in vivo administration of biological substances usable for this purpose and compositions

Also Published As

Publication number Publication date Type
WO1999058149A1 (en) 1999-11-18 application

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