CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)(2024)
摘要
The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, a first-in-class peptide-based radiotracer, [68 Ga]Ga-AJ206, is developed that can be seamlessly integrated into the standard clinical workflow and is specifically designed to noninvasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). A bicyclic peptide, AJ206, is synthesized and exhibits high affinity to CD38 (KD : 19.1 ± 0.99 × 10-9 m) by surface plasmon resonance. Further, [68 Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [68 Ga]Ga-AJ206 detects CD38 expression in cell line-derived xenografts, patient-derived xenografts (PDXs), and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68 Ga]Ga-AJ206-PET successfully quantifies CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following all-trans retinoic acid (ATRA) therapy. In conclusion, [68 Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [68 Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.
更多查看译文
关键词
ATRA,CD38,daratumumab,isatuximab,PET,pharmacodynamics
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要