Associate Professor Zucker SOM-Northwell NS/LIJ, United States
Learning Objectives: Explain alpha particles' physical properties and clinical impact, compare systemic versus IR-guided alpha therapy delivery, describe IR-guided alpha therapy techniques and outcomes, evaluate locoregional alpha therapy for challenging tumors, and apply alpha-specific radiation safety protocols.
Background: The convergence of interventional radiology (IR) and alpha-emitter theranostics transforms precision oncology by overcoming systemic delivery limitations. Locoregional IR techniques including intratumoral implantation, intra-arterial delivery, and intracavitary administration maximize tumor exposure while minimizing systemic radiation, leveraging alpha particles' ultra-short range for concentrated cytotoxic effects {1-14}. By providing direct access to tumors and enabling controlled regional distribution, IR transforms alpha theranostics from a systemic therapy with dose-limiting toxicities into a precision tool capable of delivering tumoricidal doses with minimal adverse effects.
Clinical Findings/Procedure Details: Clinical and preclinical studies demonstrate targeted alpha therapy's safety and efficacy across multiple delivery routes. Intratumoral 224Ra wires create millimeter-scale destruction zones with minimal toxicity {1, 2}. Intraperitoneal approaches with 211At-antibodies and 212Pb-trastuzumab achieved tumor control in ovarian and HER2-positive cancers while 224Ra microparticles eliminated all peritoneal recurrences at 18 months post-CRS-HIPEC {3-6}. Intra-arterial 213Bi-DOTATOC overcomes beta-resistance in liver metastases {7}. By leveraging alpha particles' sub-0.1mm penetration, these regional strategies enable precise micrometastasis destruction while preserving healthy tissues. Alpha particles' < 100 μm range cannot penetrate skin, producing negligible external radiation (< 0.5 µSv/hr) and eliminating isolation requirements {15, 16}. Safety focuses on preventing internal contamination via PPE, hygiene protocols, and zinc sulfide monitoring. This ultra-short range enables precise tumor ablation while allowing immediate discharge.
Conclusion and/or Teaching Points: IR overcomes systemic alpha therapy limitations by maximizing therapeutic dose while preserving alpha particles' ultra-short range advantage. Clinical evidence demonstrates superior tumor control, ability to overcome treatment-resistant disease, favorable safety profile, and minimal systemic exposure. IR's direct tumor access and imaging guidance transforms alpha therapy into an effective precision theranostics platform for resistant malignancies.
