CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.

ABSTRACT: 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, [⁶⁸Ga]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 (K_D: 19.1 ± 0.99 × 10^-9 m) by surface plasmon resonance. Further, [⁶⁸Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [⁶⁸Ga]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, [⁶⁸Ga]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, [⁶⁸Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [⁶⁸Ga]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.

SUBMITTER: Sharma AK 

PROVIDER: S-EPMC11040352 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature