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内容記述 |
Background/Purpose: Metabotropic glutamate receptor 1 (mGluR1) is highly expressed in various cancer types, including melanoma, making it a promising target for radiotheranostics (1-3). This study aimed to develop novel radiopharmaceuticals that integrate positron emission tomography (PET) imaging and targeted alpha therapy (TAT) for cancer detection and treatment (Fig.1).Methods: Two radiopharmaceutical compounds were synthesized: 3-iodo- N-[4-[6-(methylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-[11C]methylbenzamide ([11C]IMTM) for PET imaging and 3-211At-astato-N-[4-[6-(methylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([211At]AMTM) for TAT (Fig.1A). Their diagnostic and therapeutic efficacy was evaluated in vitro using melanoma B16F10 cell lines and in vivo in corresponding tumor-bearing mouse models.Results: Both [11C]IMTM and [211At]AMTM exhibited high binding affinity to B16F10 cells. PET imaging with [11C]IMTM successfully visualized tumors in subcutaneous and lung metastatic melanoma models (Fig.1B). A single intravenous dose of [211At]AMTM (2.96 MBq) significantly reduced tumor size to less than 10% of the untreated group (7.79 ± 1.59 cm³ vs. 0.64 ± 0.45 cm³) by day 16 post-treatment in subcutaneous melanoma models, and extended survival by 3-times in lung metastatic melanoma models (Fig. 1C). No significant body weight loss or adverse effects on liver or kidney function were observed in treated mice during the study period.Conclusion: The novel radiopharmaceuticals [11C]IMTM and [211At]AMTM demonstrate strong potential as radiotheranostic agents targeting mGluR1. They offer precise and effective diagnostic and therapeutic options for refractory cancers, such as melanoma, and hold promise for future clinical application in radiotheranostics.References1. Pollock PM, et al. Nat Genet. 2003; 34:108-112.2. Xie L, et al. J Nucl Med. 2020;61:242-248. 3. Xie L, et al. Cell Rep Med. 2023;4:100960. |
