Targeted alpha therapy for solid tumors: biological rationale, clinical advances, and future perspectives
Abstract
Targeted alpha therapy (TAT) delivers high-linear-energy-transfer radiation over a few cell diameters and is being explored for resistant and microscopic solid-tumor disease. This targeted narrative review evaluates alpha-emitting platforms and clinical evidence by tumor type and development stage, with a focused literature update through 12 October 2026. Unlike broader radiochemistry-centered reviews, we place approved, randomized, early-phase, observational, and preclinical findings in separate evidence tiers. Radium-223 dichloride has randomized survival evidence in symptomatic bone-metastatic castration-resistant prostate cancer, whereas molecularly targeted actinium-225, lead-212, astatine-211, and thorium-227 agents remain investigational in the indications discussed. Updated examples include the 2026 ACTION-1 actinium-225-DOTATATE dosimetry substudy, the 2026 first-in-human astatine-211-MABG study, 2025 lead-212-DOTAMTATE phase II disclosures, and a negative 2025 mesothelin-targeted thorium-227 study. Quantitative outcomes are reported with their study design and limitations rather than interpreted as indirect head-to-head comparisons. Major barriers include isotope supply, incomplete daughter retention, salivary, marrow, and kidney toxicity, spatially heterogeneous target uptake, and uncertainty in patient-specific microdosimetry. We propose practical, imaging-led selection and a priority-ranked translational roadmap.
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BibTeX
@article{li2026targeted,
title = {{Targeted alpha therapy for solid tumors: biological rationale, clinical advances, and future perspectives}},
author = {Qimin Li and Jian Xie and Fei Chen and Laixiang Li and Chuansheng Yang},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.2007300},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.2007300},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Targeted alpha therapy for solid tumors: biological rationale, clinical advances, and future perspectives
AU - Qimin Li
AU - Jian Xie
AU - Fei Chen
AU - Laixiang Li
AU - Chuansheng Yang
PY - 2026
DA - 2026/11/02
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.2007300
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.2007300
AB - Targeted alpha therapy (TAT) delivers high-linear-energy-transfer radiation over a few cell diameters and is being explored for resistant and microscopic solid-tumor disease. This targeted narrative review evaluates alpha-emitting platforms and clinical evidence by tumor type and development stage, with a focused literature update through 12 October 2026. Unlike broader radiochemistry-centered reviews, we place approved, randomized, early-phase, observational, and preclinical findings in separate evidence tiers. Radium-223 dichloride has randomized survival evidence in symptomatic bone-metastatic castration-resistant prostate cancer, whereas molecularly targeted actinium-225, lead-212, astatine-211, and thorium-227 agents remain investigational in the indications discussed. Updated examples include the 2026 ACTION-1 actinium-225-DOTATATE dosimetry substudy, the 2026 first-in-human astatine-211-MABG study, 2025 lead-212-DOTAMTATE phase II disclosures, and a negative 2025 mesothelin-targeted thorium-227 study. Quantitative outcomes are reported with their study design and limitations rather than interpreted as indirect head-to-head comparisons. Major barriers include isotope supply, incomplete daughter retention, salivary, marrow, and kidney toxicity, spatially heterogeneous target uptake, and uncertainty in patient-specific microdosimetry. We propose practical, imaging-led selection and a priority-ranked translational roadmap.
SN - 2234-943X
ER -