IP Library Granted Patent US 12,440,587
Granted Patent B2
US 12,440,587 · App. 18/407,111 · Granted Oct 14, 2025

Particles functionalized with imageable radioisotopes and methods of making and use thereof

Inventors: James Radford Stone (Charlottesville, VA); Kiel Douglas Neumann (Charlottesville, VA); Matthew Robert Dreher (Dover, MA)
Assignees: Boston Scientific Medical Device Limited; University of Virginia Patent Foundation
A61K51/1244A61B6/037A61K51/02A61N5/1001A61N2005/1021A61N2005/1052
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Quick Facts
Patent No.
US 12,440,587
App. No.
18/407,111
Granted
Oct 14, 2025
Kind
B2
Abstract

Some embodiments relate to imageable radioisotopic microspheres. In some embodiments, the imageable microspheres are radiolabeled with imageable radioisotopes. In some embodiments, the imageable radioisotope is directly coupled to a surface of a substrate of the microsphere. In some embodiments, the imageable microspheres can be used as surrogate particles to predict the distribution of therapeutic microspheres comprising radiotherapeutic isotopes.

Claims (52)

1. A method for determining an amount of therapeutic microspheres to provide to a body of a patient, the method comprising:

delivering a population of imageable microspheres to the patient by introducing the population of imageable microspheres to a first position in a vasculature of the patient;

allowing the population of imageable microspheres to distribute within the body of the patient;

determining a distribution of at least a portion of the population of the imageable microspheres within the body of the patient by imaging a portion of the body of the patient using an imaging modality; and

using the distribution of the imageable microspheres to calculate an amount of therapeutic microspheres to be delivered to the body of the patient;

the imageable microspheres comprising a substrate and at least one imageable radioisotope bound to a surface of the substrate;

wherein the substrate comprises silicon dioxide and at least one other element selected from manganese, aluminum, gallium, yttrium, boron, strontium, and titanium;

wherein the at least one imageable radioisotope is selected from 99m Tc, 201 Th, 51 Cr, 67 Ga, 68 Ga, 111 In, 64 Cu, 89 Zr, 59 Fe, 42 K, 82 Rb, 24 Na, 45 Ti, 44 Sc, 51 Cr, 177 Lu, 18 F, and/or combinations thereof; and

wherein the at least one imageable radioisotope is bound directly to the surface of the substrate through non-metal atoms of the substrate and/or wherein the at least one imageable radioisotope is bound to the surface of the substrate through an inorganic bridge comprising the non-metal atoms of the substrate.

2. The method of claim 1 , wherein the portion of the body is an off-target area of the patient and the off-target area is a lung of the patient.

3. The method of claim 1 , wherein the portion of the body is a target area of the patient and the target area is a liver of the patient.

4. The method of claim 1 , wherein the portion of the body is a target area of the patient and the target area is divided into tumor and non-tumor tissue.

5. The method of claim 1 , wherein the amount calculated is delivered to the patient.

6. The method of claim 1 , wherein the imaging modality is SPECT.

7. The method of claim 1 , wherein the imaging modality is PET.

8. The method of claim 1 , wherein the imaging modality is gamma camera imaging.

9. The method of claim 1 , wherein the at least one imageable radioisotope is selected from 99m Tc and 89 Zr.

10. The method of claim 1 , further comprising:

obtaining data regarding a distribution of the imageable microspheres in the patient;

using the data to determine the amount of the therapeutic microspheres to administer to the body of the patient;

delivering a population of the therapeutic microspheres to the patient by introducing the population of the therapeutic microspheres to a second position in the vasculature of the body of the patient; and

allowing the population of the therapeutic microspheres to distribute within the body of the patient, thereby treating the patient.

11. The method of claim 10 wherein the second position in the vasculature of the patient is the same as the first position in the vasculature of the patient or is proximate the same position.

12. The method of claim 10 , wherein the imaging modality is SPECT.

13. The method of claim 10 , wherein the imaging modality is PET.

14. The method of claim 10 , wherein the imaging modality is a gamma camera imaging.

15. The method of claim 1 , wherein the substrate comprises yttrium aluminum silicon oxide.

16. A method for determining an amount of therapeutic microspheres to provide to a body of a patient, the method comprising:

delivering a population of imageable microspheres to the patient by introducing the population of imageable microspheres to a first position in a vasculature of the patient;

allowing the population of imageable microspheres to distribute within the body of the patient;

determining a distribution of at least a portion of the population of the imageable microspheres within the body of the patient by imaging a portion of the body of the patient using an imaging modality; and

using the distribution of the imageable microspheres to calculate an amount of therapeutic microspheres to be delivered to the body of the patient;

the imageable microspheres comprising a substrate and at least one imageable radioisotope bound to a surface of the substrate;

wherein the substrate comprises silicon dioxide and at least one other element selected from manganese, aluminum, gallium, yttrium, boron, strontium, and titanium;

wherein the at least one imageable radioisotope is selected from 99m Tc, 201 Th, 51 Cr, 67 Ga, 68 Ga, 111 In, 64 Cu, 89 Zr, 59 Fe, 42 K, 82 Rb, 24 Na, 45 Ti, 44 Sc, 51 Cr, 177 Lu, 18 F, and/or combinations thereof;

wherein the substrate comprises a core extending to the surface, the core comprising a first portion of metalloid or metal atoms bonded to non-metal atoms and the surface comprising a second portion of the metalloid or metal atoms bonded to the non-metal atoms; and

wherein the at least one imageable radioisotope is bound directly to the substrate through the non-metal atoms of the surface of the substrate and/or wherein the at least one imageable radioisotope is bound to the substrate through an inorganic bridge comprising the non-metal atoms of the surface of the substrate.

17. A method for determining an amount of therapeutic microspheres to provide to a body of a patient, the method comprising:

delivering a population of imageable microspheres to the patient by introducing the population of imageable microspheres to a first position in a vasculature of the patient;

allowing the population of imageable microspheres to distribute within the body of the patient;

determining a distribution of at least a portion of the population of the imageable microspheres within the body of the patient by imaging a portion of the body of the patient using an imaging modality;

using the distribution of the imageable microspheres to calculate an amount of therapeutic microspheres to be delivered to the body of the patient;

obtaining data regarding a distribution of the imageable microspheres in the patient;

using the data to determine the amount of the therapeutic microspheres to administer to the body of the patient;

delivering a population of the therapeutic microspheres to the patient by introducing the population of the therapeutic microspheres to a second position in the vasculature of the body of the patient; and

allowing the population of the therapeutic microspheres to distribute within the body of the patient, thereby treating the patient;

the imageable microspheres comprising a substrate and at least one imageable radioisotope bound to a surface of the substrate;

wherein the substrate comprises silicon dioxide and at least one other element selected from manganese, aluminum, gallium, yttrium, boron, strontium, and titanium;

wherein the at least one imageable radioisotope is selected from 99m Tc, 201 Th, 51 Cr, 67 Ga, 68 Ga, 111 In, 64 Cu, 89 Zr, 59 Fe, 42 K, 82 Rb, 24 Na, 45 Ti, 44 Sc, 51 Cr, 177 Lu, 18 F, and/or combinations thereof;

wherein the substrate comprises a core extending to a surface, the core comprising a first portion of metalloid or metal atoms bonded to non-metal atoms and the surface comprising a second portion of the metalloid or metal atoms bonded to the non-metal atoms; and

wherein the at least one imageable radioisotope is bound directly to the substrate through the non-metal atoms of the surface of the substrate and/or wherein the at least one imageable radioisotope is bound to the substrate through an inorganic bridge comprising the non-metal atoms of the surface of the substrate.

18. The method of claim 17 , wherein the at least one imageable radioisotope is selected from 99m Tc and 89 Zr.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2024
From: STONE, JAMES RADFORD; NEUMANN, KIEL DOUGLAS
To: UNIVERSITY OF VIRGINIA
Reel/Frame 066115/0342 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2024
From: UNIVERSITY OF VIRGINIA
To: UNIVERSITY OF VIRGINIA PATENT FOUNDATION
Reel/Frame 066115/0412 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2024
From: DREHER, MATTHEW ROBERT
To: BOSTON SCIENTIFIC MEDICAL DEVICE LIMITED
Reel/Frame 066115/0483 →
Continuity (3)
Division 17166820 · Feb 3, 2021
Provisional Application 62970587 · Feb 5, 2020
Related Publication 20240139354A1 · May 2, 2024
References Cited (11)
US 20060177373A1 · Ruys et al. · 2006 [cited by applicant]
US 20080038190A1 · Simpson · 2008 [cited by examiner]
US 20090016960A1 · Selwyn · 2009 [cited by examiner]
US 20150118495A1 · Day et al. · 2015 [cited by applicant]
US 20170143857A1 · Day et al. · 2017 [cited by applicant]
US 20220177351A1 · Legere et al. · 2022 [cited by applicant]
Chen et al., “In Vivo Integrity and Biological Fate of Chelator-Free Zirconioum-89-Labeled Mesoporous Silica Nanoparticles,” ACS Nano, vol. 9, No. 8, pp. 7950-7959, 2015. (Year:2015). [cited by applicant]
Liapi et al., “Radioembolization for Hepatocellular Carcinoma”, Dec. 23, 2015 (Dec. 23, 2015), XP093159908, Retrieved from the Internet: URL: https://radiologykey.com/radioembolization-for-hepatocellular-carcinoma/. [cited by applicant]
Partial Supplementary European Search Report for European Application No. 21750243.4, dated Aug. 20, 2024. [cited by applicant]
Ito., “Improvement of 89Sr and 90Y bremstrahlung emission computed tomography”, Grants-in-Aid for Scientific Research: Research Results Report, pp. 1-5, https://kaken.nii.ac.jp/ja/file/KAKENHI-PROJECT-23591778/23591778s… [cited by applicant]
Nijsen et al., “Advances in Nuclear Oncology: Microspheres for Internal Radionuclide Therapy of Liver Tumours”, Current Medicinal Chemistry, 2002, vol. 9, pp. 73-82. [cited by applicant]