ASTATINE-211 PRODUCTION UPDATE FOR THE UNIVERSITY OF WASHINGTON - - PowerPoint PPT Presentation

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ASTATINE-211 PRODUCTION UPDATE FOR THE UNIVERSITY OF WASHINGTON - - PowerPoint PPT Presentation

Mar 31, 2024 142 likes •287 views

UW MEDICINE DEPARTMENT OF RADIATION ONCOLOGY ASTATINE-211 PRODUCTION UPDATE FOR THE UNIVERSITY OF WASHINGTON 2020 DOE IP ASTATINE-211 USER MEETING ROB EMERY YAWEN LI 7/28/2020 DOE FUNDING UW Medical Cyclotron Facility under DOE Isotope

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UW MEDICINE │ DEPARTMENT OF RADIATION ONCOLOGY

ASTATINE-211 PRODUCTION UPDATE FOR THE UNIVERSITY OF WASHINGTON

2020 DOE IP ASTATINE-211 USER MEETING

ROB EMERY YAWEN LI 7/28/2020

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UW Medical Cyclotron Facility under DOE Isotope Program stewardship

  • DOE base funding partially supporting cyclotron operations
  • Radionuclide production under DOE guidance

Radiochemistry Division is funded through Base & R&D Funding obtained from DOE Isotope Program

  • Currently providing At-211 through NIDC; supported by equipment and base

funding (started June 2015)

  • Developing other radionuclide production through R&D Funding
  • Will provide other radionuclides when production routes are achieved, and facilities are

adequate for high levels of activity

DOE FUNDING

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UW MEDICAL CYCLOTRON FACILITY - CAPACITY

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0% 1% 2% 3% 4% 5% 6% 7% 8% 9% 10% 11% 12% 13% 14% 15% 16%

Unscheduled Downtime

(Based on 208 days/yr, 10 hrs/day)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Available Capacity

(Based on 208 days/yr, 10 hrs/day)

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SLIDE 4

Research Target Station

UW MEDICAL CYCLOTRON FACILITY – FACILITY UPGRADE

Production Target Station

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Improved Quad Focusing New Switching Magnet Adds Ports Added Quad for Focusing New Research Target Station Production Target Station

UW MEDICAL CYCLOTRON FACILITY – FACILITY UPGRADE

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SLIDE 6

UW MEDICAL CYCLOTRON FACILITY – FACILITY UPGRADE

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SLIDE 7

UW MEDICAL CYCLOTRON FACILITY – FACILITY UPGRADE

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SLIDE 8

OVERVIEW OF ASTATINE-211 PRODUCTION AND RESEARCH ACTIVITIES

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YEARLY ASTATINE-211 PRODUCTION

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457.6 mCi produced Jan-Jun, 2020

  • Production for NIDC,

preclinical and clinical research

  • Automation of isolation
  • Blood-borne diseases
  • Targeting T-cells

harboring latent HIV virus

  • Gene therapy with HCT
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ASTATINE-211 PRODUCED FOR CLINICAL TRIALS

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  • Two 211At-BC8-B10 Phase I/II clinical trials on-going

 NCT03128034, P.I. Dr. Brenda Sandmaier, MD, started Oct, 2017  NCT04083183, P.I. Dr. Phuong Vo, MD, started June, 2020

  • Have treated a total of 26 patients
  • Produced 3.213 Ci for patient treatment
  • Applying IND for 211At-labeled anti-CD38 MAb for

multiple myeloma treatment

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SLIDE 11

FUNDED PRECLINICAL RESEARCH USING ASTATINE-211

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  • A. Automation of 211At Isolation
  • 1. Dr. Yawen Li (UW), DOE (DE-SC0013618)

Production, Quality Control and Shipment of Radionuclides from the University of Washington

  • B. Treatment of Blood-Borne Cancers with 211At-labeled MAbs and HCT
  • 2. Dr. Damian Green (Fred Hutch), NIH (R01CA076287)

Pretargeted Radioimmunotherapy of CD20+ Lymphomas

  • 3. Dr. Roland Walter (Fred Hutch), NIH (R37 CA240832)

Novel Approaches to CD33-Directed Radioimmunotherapy

  • 4. Dr. Johnnie Orozco (Fred Hutch), NIH (R37 CA252070)

Combining Targeted RIT and Synergistic Novel Agents to Eradicate AML

  • 5. Dr. Damian Green (Fred Hutch), NIH (R01CA205248)

Anti-CD38 targeted alpha-emitter radioimmunotherapy to eliminate multiple myeloma

  • 6. Dr. Roland Walter (Fred Hutch), ASH (0001002414)

Development of Alpha-Emitting Anti-CD123 Radioimmunotherapy for Cancer (Stem) Cell-Directed Treatment of Acute Leukemias and Other Hematologic Malignancies

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FUNDED PRECLINICAL RESEARCH USING ASTATINE-211 (CONT’D)

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  • C. Treatment of HIV Infected Cells
  • 7. Dr. Brenda Sandmaier (Fred Hutch), NIH (R33AI116225)

Alpha Emitter Labeled Anti-T-Cell Antibody: Targeting Latent HIV Infected Cells

  • 8. Dr. Seth Pincus/Dr. Robert Harrington (U. Mont./Fred Hutch/UW),

NIH (1R01AI136758) Cytotoxic immunoconjugates to deplete persistent HIV reservoirs

  • D. Gene Therapy with HCT
  • 9. Dr. Rainer Storb (Fred Hutch), NIH/NHLB (P01HL122173)

Cell and Gene Therapy for Nonmalignant Blood Disorders

  • 10. Dr. Roland Walter/Dr. Hans-Peter Kiem (Fred Hutch), NIH/NHLB

(R01 HL151765) Development of 211Astatine-Conjugated Anti-CD45 Antibody-Based Conditioning for Hematopoietic Stem Cell Gene Therapy and Editing

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TELLURIUM-PACKED COLUMN METHOD

  • Eliminated the nitric acid distillation step
  • Hydroxylamine hydrochloride is used to

destroy the nitrate

  • Final product contains tellurium impurity

(i.e. Na2TeO3) ~20-50 ppm

  • Might have residual hydroxylamine

hydrochloride in the final product

  • Process takes ~1.5 h
  • Final product in ~1 mL NaOH
  • Process still needs to be optimized
  • Decay and attenuation corrected isolation

yields: >95%

  • Non-decay corrected yield: ~90%

Te column Li, Y., Hamlin, D.K., Chyan, M. et al. Sci Rep 9, 16960(2019).

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QUESTIONS?

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