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Isolating Malignant and Non-Malignant B Cells from lck:eGFP Zebrafish

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Targeted Alpha-Particle Therapy for Hematologic Malignancies.

Joseph G Jurcic¹

¹Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center, New York-Presbyterian Hospital, Herbert Irving Comprehensive Cancer Center, New York, New York, USA.

Journal of Medical Imaging and Radiation Sciences

|June 30, 2019

Summary

Targeted alpha therapy using actinium-225 lintuzumab shows promise for treating acute myeloid leukemia (AML). This approach demonstrated significant antileukemic activity and induced remissions in patients, supporting further development for hematologic malignancies.

Keywords:

Acute myeloid leukemia CD33 actinium-225 alpha-particle bismuth-213 multiple myeloma myelodysplastic syndrome radioimmunotherapy

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Published on: November 12, 2019

Area of Science:

Oncology
Nuclear Medicine
Radiopharmaceutical Therapy

Background:

Alpha particles offer potent tumor cell killing with minimal damage to surrounding normal tissues.
Hematologic malignancies are suitable targets for alpha-particle therapy due to accessible malignant cells and their radiosensitivity.

Purpose of the Study:

To evaluate the safety and efficacy of lintuzumab, an anti-CD33 antibody, labeled with alpha-emitters bismuth-213 (213Bi) and actinium-225 (225Ac).
To assess the antileukemic effects of these targeted alpha-therapies in patients with acute myeloid leukemia (AML).

Main Methods:

Clinical trials involving lintuzumab labeled with 213Bi and 225Ac were conducted.
Dose-escalation studies (Phase I) and monotherapy/combination studies (Phase II) were performed in AML patients.

Main Results:

213Bi-lintuzumab demonstrated antileukemic activity and induced remissions when combined with cytarabine.
225Ac-lintuzumab was safely administered, showing dose-dependent antileukemic activity.
Objective responses were observed in 28% of older, untreated AML patients receiving fractionated 225Ac-lintuzumab with low-dose cytarabine.
Monotherapy with 225Ac-lintuzumab resulted in remissions in 69% and 22% of patients in a Phase II study, depending on the fractionated dose.

Conclusions:

213Bi-lintuzumab provided proof of principle for systemic alpha-particle therapy.
225Ac-lintuzumab showed activity in advanced AML and produced remissions in older, untreated AML patients.
These findings support the further development of 225Ac-lintuzumab for AML and other hematologic malignancies like myelodysplastic syndrome and multiple myeloma.