The nuclide ${}^{262}\mathrm{Db}$ was produced in the ${}^{248}\mathrm{Cm}$(${}^{19}\mathrm{F}$,5$n$)${}^{262}\mathrm{Db}$ reaction at beam energies of 103.1 and 97.4 MeV. Decay properties of ${}^{262}\mathrm{Db}$ were investigated with a rotating wheel apparatus for α and spontaneous fission (SF) spectrometry under low background conditions attained by a gas-jet transport system coupled to the RIKEN gas-filled recoil ion separator. Based on genetically correlated α-α and α-SF decay chains, a total of 76 chains were assigned to ${}^{262}\mathrm{Db}$ and its α-decay daughter nuclide ${}^{258}\mathrm{Lr}$. No correlated decay chain was observed for Db produced in the ${}^{248}\mathrm{Cm}$(${}^{19}\mathrm{F}$,4$n$)Db reaction and its daughter Lr. The half-lives of ${}^{262}\mathrm{Db}$ and ${}^{258}\mathrm{Lr}$ were measured to be $T_{1/2}=33.8_{-3.5}^{+4.4}$ and $3.{54}_{-0.36}^{+0.46}\mathrm{s}$, respectively, and they confirmed the literature data. The α-particle energy $\left(E_{\alpha }\right)$ and intensity ($I_{\alpha }$) of ${}^{262}\mathrm{Db}$ were revised to $E_{\alpha }$ = 8.46 ± 0.04 MeV ($I_{\alpha }$ = 70 ± 5%) and $E_{\alpha }$ = 8.68 ± 0.03 MeV ($I_{\alpha }$ = 30 ± 5%). The SF activity with $T_{1/2}$ = 30.2 ± 6.1 s was assigned to ${}^{262}\mathrm{Db}$, and the SF branch of ${}^{262}\mathrm{Db}$ was determined to be $b_{\mathrm{SF}}$ = 52 ± 4%. From an observation of two SF decays which correlated to the α decay of ${}^{262}\mathrm{Db}$, an electron capture (EC) decay with $b_{\mathrm{EC}}$ = 2.6 ± 1.8% was suggested in ${}^{258}\mathrm{Lr}$. The production cross sections for the ${}^{248}\mathrm{Cm}$(${}^{19}\mathrm{F}$,5$n$)${}^{262}\mathrm{Db}$ reaction were determined to be 2.1 ± 0.7 nb at 103.1 MeV and $0.{23}_{-0.11}^{+0.18}\mathrm{nb}$ at 97.4 MeV, whereas, those for the ${}^{248}\mathrm{Cm}$(${}^{19}\mathrm{F}$,4$n$)Db reaction were the upper limits of ≤0.064 nb at 103.1 MeV and ≤0.13 nb at 97.4 MeV. These cross sections are discussed by comparing with the literature data as well as the theoretical prediction.

Astatine (²¹¹At) is an alpha-emitting nuclide with a 7.2-hour half-life that can be produced using a 30-MeV cyclotron. In recent years, the number of production sites worldwide has been increasing, attracting growing attention to ²¹¹At. We have developed a novel ²¹¹At-labeled PSMA-targeted agent ([²¹¹At]PSMA-5). After conducting preclinical evaluations of its antitumor efficacy and safety, we initiated a first-in-human, investigator-initiated clinical trial in patients with metastatic castration-resistant prostate cancer. To date, the drug has been administered to a total of nine patients, and we have reported high accumulation of [²¹¹At]PSMA-5 in recurrent and metastatic lesions. While further efforts are required for the social implementation of ²¹¹At-based targeted alpha therapy, including the establishment of a supply chain and the accumulation of additional clinical evidence, PSMA-targeted alpha therapy using ²¹¹At represents a promising treatment modality owing to its cyclotron-based production, sustainability, and clean decay characteristics.

We investigated nuclear medicine therapeutics targeting the L-type amino acid transporter 1 (LAT1). We previously reported that a nuclear medicine therapeutic drug using astatine 211 (²¹¹At), an alpha-emitting nuclide that can be produced in an accelerator and targets LAT1 as a molecular target, is effective. The seed compound was 3-[²¹¹At] Astato-α-methyl-L-tyrosine (²¹¹At-AAMT-OH-L). We used a unique labeling method. By changing the OH group of phenol to a methyl group, retention was successfully increased. It was also found that the amount of the L-isomer taken up by the D-isomer and L-isomer was clearly higher, and the L-isomer was superior as a therapeutic drug. Compounds in which the methyl group was replaced with an ethyl or propyl group were also examined, but their retention did not increase significantly. In fact, we observed increased non-specific accumulation and dynamics, suggesting that labeling may be off. In addition, ²¹¹At-AAMT-O-Me-L, which has a simple structure, was clearly superior in terms of uptake speed for several candidate compounds. As a result, we were able to develop a compound that can be easily labeled, has high specific radioactivity, is stable, and has a strong therapeutic effect.

Novel nuclear medicine therapeutics are being developed by labeling medium-molecular-weight compounds with short-lived alpha-emitting radionuclides. Fibroblast activation protein α (FAPα) is recognized as a highly useful molecular target, and its inhibitor, FAPI, is a compound capable of theranostics, both therapeutic and diagnostic, for cancer treatment. In this study, we compared the functions of two compounds that target FAPα: ²¹¹At-FAPI1 and ²¹¹At-FAPI2. First, in vitro screening procedures are generally accepted because of the low endogenous expression of FAPα. We suggest the usefulness of this 3D culture system for in vitro screening. Second, when FAPIs are used therapeutically, the expected therapeutic effects are often not achieved. Therefore, we compared the accumulation and excretion in tumor tissues and the anti-tumor effects based on the length of the linker in the compounds. The compounds were rapidly labeled using the Shirakami reaction. Doubling the linker length increased tumor retention. Additionally, the excretion pathway was altered, suggesting a potential reduction in toxicity. Although no significant differences were observed in the anti-tumor effects of ²¹¹At-FAPI1 and ²¹¹At-FAPI2, it was confirmed that the linker length affects the biological half-life.