Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, with therapeutic resistance posing the primary barrier to durable outcomes. Beyond genetic and epigenetic alterations, amino acid transporter-driven metabolic reprogramming—mediated by LAT1 (SLC7A5), ASCT2 (SLC1A5), and xCT (SLC7A11)—supports tumor proliferation, redox homeostasis, and immune escape. Their preferential expression in NSCLC highlights their potential as therapeutic targets and predictive biomarkers. In parallel, α-particle therapy has gained attention for its capacity to eradicate resistant clones through densely clustered, irreparable DNA double-strand breaks. Astatine-211 (²¹¹At) combines a clinically relevant half-life, high linear energy transfer, and predictable decay scheme, positioning it as a unique candidate among α-emitters. Preclinical studies of ²¹¹At-labeled transporter ligands, particularly LAT1-targeted conjugates, demonstrate potent tumor suppression and synergy with targeted therapy, chemotherapy, radiotherapy, immunotherapy, and ferroptosis inducers. Advances in radiochemistry, delivery systems (antibodies, peptides, and nanocarriers), and PET tracers such as [¹⁸F]FAMT and [¹⁸F]FSPG collectively support a theranostic framework for patient stratification and adaptive dosing. By linking transporter biology with α-particle delivery, ²¹¹At-based theranostics offer a mechanistically orthogonal strategy to overcome resistance and heterogeneity in NSCLC. Successful translation will depend on precise dosimetry, scaffold stabilization, and biomarker-guided trial design, enabling progression toward first-in-human studies and future integration into multimodal NSCLC therapy.

This study investigated the distribution and dispersion of Sc-47 (⁴⁷Sc), a β-emitting radionuclide that can be produced in large quantities using accelerators. As the stability of labeled compounds inside the body is essential for nuclear medicine therapy, we examined the biodistribution of free ⁴⁷Sc to distinguish it from the distribution of compounds labeled with ⁴⁷Sc. [⁴⁷Sc]ScCl₃ was administered to normal mice. Body distribution, excretion routes, and contamination of laboratory equipment were also measured. ⁴⁷Sc remained in the blood for long periods and accumulated mainly in the liver and kidneys because of its binding to plasma proteins. Therefore, ⁴⁷Sc released from the labeled compounds could potentially cause non-specific liver and kidney damage. Most of the ⁴⁷Sc was eliminated through feces, whereas some was excreted through the urinary system. ⁴⁷Sc was found in both the liquid and solid components of the blood. Although animal cages were contaminated with excreta, they could be effectively cleaned by wiping with paper. We also used ⁴⁷Sc produced by us to label PSMA-617 and verified its performance as a nuclear medicine therapeutic agent. Although [⁴⁷Sc]Sc-PSMA-617 did not exhibit a high accumulation rate in tumors, it demonstrated antitumor activity. This might suggest the usefulness of ⁴⁷Sc.