Case study #1: Alpha particle therapy of leukemia using (225)Ac-lintuzumab Book Section
| Author: | McDevitt, M. R. |
| Editors: | Bodei, L.; Lewis, J. S.; Zeglis, B. M. |
| Article/Chapter Title: | Case study #1: Alpha particle therapy of leukemia using (225)Ac-lintuzumab |
| Abstract: | 225Ac-Lintuzumab (Actimab-A, Actinium Pharmaceuticals, Inc.) is an alpha particle emitting monoclonal antibody (mAb) drug targeting the CD33 antigen expressed on acute myeloid leukemia (AML) cells. The name “actinium” is derived from the Greek aktis meaning “ray” or “beam,” and the decay of each actinium-225 atom produces 4 alpha (α) particles during the cascade to stable 209Bi. Lintuzumab (HuM195) is a humanized immunoglobulin G (IgG) that was selected for specific bioactivity towards the CD33 antigen expressed on early myeloid cells, acute non-lymphoid leukemia cells, and monocytic cells. Humanized HuM195 was engineered from the murine M195 antibody, and both antibodies have demonstrated the ability to target leukemia cells in clinical trials without immunogenicity. The first-in-human α-emitting radioimmunoconjugate was 213Bi-Lintuzumab. However, the short radionuclidic half-life of 213Bi (t1/2 = 46 min) presented a logistical challenge, i.e., the need for on-site production with no opportunity for shipping. However, the potent anti-tumor activity of this first-generation targeted radiotherapeutic provided proof-of-concept that α-based therapy using HuM195 was tumor-specific and produced only minimal off-tumor toxicity. The next-generation radioimmunoconjugate-225Ac-lintuzumab-was armed with 225Ac, which has a much longer radionuclidic half-life: 10 d. This change resolved the key logistical issue that limited widespread use. However, at that time, the radiochemistry of 225Ac3+ was relatively unexplored, and the stable coordination of the radiometal presented unique pharmacologic challenges with respect to controlling the in vivo fate of its radioisotopic daughters. This chapter will recount the developmental evolution of 225Ac-lintuzumab, including the challenges to translate this novel drug into the clinic. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023. |
| Keywords: | leukemia; hum195; actinium-225; lintuzumab; dota; cd33; alpha particle |
| Book Title: | Radiopharmaceutical Therapy |
| ISBN: | 978-3-031-39004-3 |
| Publisher: | Springer |
| Publication Place: | Cham, Switzerland |
| Date Published: | 2023-01-01 |
| Start Page: | 215 |
| End Page: | 224 |
| Language: | English |
| DOI: | 10.1007/978-3-031-39005-0_10 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Book chapter: 10 -- Source: Scopus |
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