{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sharma AK"],"funding":["NIBIB NIH HHS","NCI NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["e2308617"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11040352"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(16)"],"pubmed_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, [<sup>68</sup>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 (K<sub>D</sub>: 19.1 ± 0.99 × 10<sup>-9</sup> m) by surface plasmon resonance. Further, [<sup>68</sup>Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [<sup>68</sup>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, [<sup>68</sup>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, [<sup>68</sup>Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [<sup>68</sup>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."],"journal":["Advanced science (Weinheim, Baden-Wurttemberg, Germany)"],"pubmed_title":["CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET."],"pmcid":["PMC11040352"],"funding_grant_id":["P30 CA006973","R01 CA236616","P41EB024495","P30CA006973","R01 CA269235","R01CA269235","R01CA236616","P41 EB024495"],"pubmed_authors":["Kumar D","Lofland G","Gocke CB","Nimmagadda S","Mishra A","Hobbs RF","Rowe SP","Imus P","Sharma AK","Gupta K","Ghiaur G","Marsh I"],"additional_accession":[]},"is_claimable":false,"name":"CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.","description":"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, [<sup>68</sup>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 (K<sub>D</sub>: 19.1 ± 0.99 × 10<sup>-9</sup> m) by surface plasmon resonance. Further, [<sup>68</sup>Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [<sup>68</sup>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, [<sup>68</sup>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, [<sup>68</sup>Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [<sup>68</sup>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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2025-04-22T20:47:36.702Z","creation":"2025-04-06T03:16:55.6Z"},"accession":"S-EPMC11040352","cross_references":{"pubmed":["38421139"],"doi":["10.1002/advs.202308617"]}}