Not listed REAL-TIME MONITORING OF NANOBUBBLE-LABELED CHIMERIC ANTIGEN RECEPTOR T CELL TRAFFICKING VIA CONTRAST-ENHANCED ULTRASOUND - PROJECT SUMMARY THE CLINICAL IMPACT OF CAR-T CELL-BASED IMMUNOTHERAPY IS CLEAR, WITH MULTIPLE FDA-APPROVED TREATMENTS NOW AVAILABLE FOR ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), B CELL AND FOLLICULAR LYMPHOMAS, AND MULTIPLE MYELOMA. BUILDING ON THIS SUCCESS, SIGNIFICANT EFFORTS ARE FOCUSED ON DEVELOPING CAR-T CELL THERAPIES FOR SOLID TUMORS. HOWEVER, LIMITATIONS IN REAL-TIME MONITORING OF CAR-T CELL BEHAVIOR AND DISTRIBUTION MAKE IT CHALLENGING TO COMPREHENSIVELY ASSESS THEIR EFFICACY AND SAFETY. WE HYPOTHESIZE THAT NANOBUBBLE-BASED ULTRASOUND CONTRAST AGENTS CAN RELIABLY LABEL PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)- TARGETING CAR-T CELLS, ENABLING REAL-TIME VISUALIZATION IN VIVO. OUR PRELIMINARY DATA SHOWS THAT NANOBUBBLES (NBS), WHICH ARE ULTRASOUND CONTRAST AGENTS WITH A LIPID SHELL SURROUNDING A C4F10 GAS CORE AND DIAMETERS OF 200-400 NM, CAN BE EFFECTIVELY INTERNALIZED BY CAR-T CELLS. THIS ALLOWS FOR DIRECT LABELING AND VISUALIZATION USING NONLINEAR CONTRAST-ENHANCED ULTRASOUND (CEUS). THE GOAL OF THIS PROPOSAL IS TO REFINE OUR LABELING PROTOCOL TO ENHANCE IMAGING DURATION AND STABILITY, ENABLING EXTENDED PSMA CAR-T CELL MONITORING IN BOTH IN VITRO AND IN VIVO SETTINGS. OUR FIRST AIM IS TO OPTIMIZE NANOBUBBLE LABELING TECHNIQUES TO ACHIEVE PROLONGED IMAGING TIMEFRAMES, ENSURING ROBUST AND SUSTAINED VISUALIZATION OF PSMA CAR-T CELLS. THE SECOND AIM FOCUSES ON ASSESSING CAR-T CELL BIODISTRIBUTION, LOCALIZATION, AND PERSISTENCE IN VIVO USING CEUS IN BOTH TUMOR-BEARING AND NON-TUMOR-BEARING MICE. THIS APPROACH WILL PROVIDE CRUCIAL INSIGHTS INTO CAR-T CELL BEHAVIOR WITHIN SOLID TUMORS. THE FINDINGS HAVE THE POTENTIAL TO ADVANCE REAL-TIME CAR-T CELL MONITORING, SUPPORTING PERSONALIZED DOSING AND TREATMENT STRATEGIES, AND CONTRIBUTING BROADLY TO CANCER IMMUNOTHERAPY, BIO-IMAGING, AND THERAPEUTIC MONITORING APPLICATIONS. $50.1k 6/12/26 Not listed REAL-TIME MONITORING OF NANOBUBBLE-LABELED CHIMERIC ANTIGEN RECEPTOR T CELL TRAFFICKING VIA CONTRAST-ENHANCED ULTRASOUND - PROJECT SUMMARY THE CLINICAL IMPACT OF CAR-T CELL-BASED IMMUNOTHERAPY IS CLEAR, WITH MULTIPLE FDA-APPROVED TREATMENTS NOW AVAILABLE FOR ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), B CELL AND FOLLICULAR LYMPHOMAS, AND MULTIPLE MYELOMA. BUILDING ON THIS SUCCESS, SIGNIFICANT EFFORTS ARE FOCUSED ON DEVELOPING CAR-T CELL THERAPIES FOR SOLID TUMORS. HOWEVER, LIMITATIONS IN REAL-TIME MONITORING OF CAR-T CELL BEHAVIOR AND DISTRIBUTION MAKE IT CHALLENGING TO COMPREHENSIVELY ASSESS THEIR EFFICACY AND SAFETY. WE HYPOTHESIZE THAT NANOBUBBLE-BASED ULTRASOUND CONTRAST AGENTS CAN RELIABLY LABEL PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)- TARGETING CAR-T CELLS, ENABLING REAL-TIME VISUALIZATION IN VIVO. OUR PRELIMINARY DATA SHOWS THAT NANOBUBBLES (NBS), WHICH ARE ULTRASOUND CONTRAST AGENTS WITH A LIPID SHELL SURROUNDING A C4F10 GAS CORE AND DIAMETERS OF 200-400 NM, CAN BE EFFECTIVELY INTERNALIZED BY CAR-T CELLS. THIS ALLOWS FOR DIRECT LABELING AND VISUALIZATION USING NONLINEAR CONTRAST-ENHANCED ULTRASOUND (CEUS). THE GOAL OF THIS PROPOSAL IS TO REFINE OUR LABELING PROTOCOL TO ENHANCE IMAGING DURATION AND STABILITY, ENABLING EXTENDED PSMA CAR-T CELL MONITORING IN BOTH IN VITRO AND IN VIVO SETTINGS. OUR FIRST AIM IS TO OPTIMIZE NANOBUBBLE LABELING TECHNIQUES TO ACHIEVE PROLONGED IMAGING TIMEFRAMES, ENSURING ROBUST AND SUSTAINED VISUALIZATION OF PSMA CAR-T CELLS. THE SECOND AIM FOCUSES ON ASSESSING CAR-T CELL BIODISTRIBUTION, LOCALIZATION, AND PERSISTENCE IN VIVO USING CEUS IN BOTH TUMOR-BEARING AND NON-TUMOR-BEARING MICE. THIS APPROACH WILL PROVIDE CRUCIAL INSIGHTS INTO CAR-T CELL BEHAVIOR WITHIN SOLID TUMORS. THE FINDINGS HAVE THE POTENTIAL TO ADVANCE REAL-TIME CAR-T CELL MONITORING, SUPPORTING PERSONALIZED DOSING AND TREATMENT STRATEGIES, AND CONTRIBUTING BROADLY TO CANCER IMMUNOTHERAPY, BIO-IMAGING, AND THERAPEUTIC MONITORING APPLICATIONS. $50.1k 6/12/26 Not listed REAL-TIME MONITORING OF NANOBUBBLE-LABELED CHIMERIC ANTIGEN RECEPTOR T CELL TRAFFICKING VIA CONTRAST-ENHANCED ULTRASOUND - PROJECT SUMMARY THE CLINICAL IMPACT OF CAR-T CELL-BASED IMMUNOTHERAPY IS CLEAR, WITH MULTIPLE FDA-APPROVED TREATMENTS NOW AVAILABLE FOR ACUTE LYMPHOBLASTIC LEUKEMIA (ALL), B CELL AND FOLLICULAR LYMPHOMAS, AND MULTIPLE MYELOMA. BUILDING ON THIS SUCCESS, SIGNIFICANT EFFORTS ARE FOCUSED ON DEVELOPING CAR-T CELL THERAPIES FOR SOLID TUMORS. HOWEVER, LIMITATIONS IN REAL-TIME MONITORING OF CAR-T CELL BEHAVIOR AND DISTRIBUTION MAKE IT CHALLENGING TO COMPREHENSIVELY ASSESS THEIR EFFICACY AND SAFETY. WE HYPOTHESIZE THAT NANOBUBBLE-BASED ULTRASOUND CONTRAST AGENTS CAN RELIABLY LABEL PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA)- TARGETING CAR-T CELLS, ENABLING REAL-TIME VISUALIZATION IN VIVO. OUR PRELIMINARY DATA SHOWS THAT NANOBUBBLES (NBS), WHICH ARE ULTRASOUND CONTRAST AGENTS WITH A LIPID SHELL SURROUNDING A C4F10 GAS CORE AND DIAMETERS OF 200-400 NM, CAN BE EFFECTIVELY INTERNALIZED BY CAR-T CELLS. THIS ALLOWS FOR DIRECT LABELING AND VISUALIZATION USING NONLINEAR CONTRAST-ENHANCED ULTRASOUND (CEUS). THE GOAL OF THIS PROPOSAL IS TO REFINE OUR LABELING PROTOCOL TO ENHANCE IMAGING DURATION AND STABILITY, ENABLING EXTENDED PSMA CAR-T CELL MONITORING IN BOTH IN VITRO AND IN VIVO SETTINGS. OUR FIRST AIM IS TO OPTIMIZE NANOBUBBLE LABELING TECHNIQUES TO ACHIEVE PROLONGED IMAGING TIMEFRAMES, ENSURING ROBUST AND SUSTAINED VISUALIZATION OF PSMA CAR-T CELLS. THE SECOND AIM FOCUSES ON ASSESSING CAR-T CELL BIODISTRIBUTION, LOCALIZATION, AND PERSISTENCE IN VIVO USING CEUS IN BOTH TUMOR-BEARING AND NON-TUMOR-BEARING MICE. THIS APPROACH WILL PROVIDE CRUCIAL INSIGHTS INTO CAR-T CELL BEHAVIOR WITHIN SOLID TUMORS. THE FINDINGS HAVE THE POTENTIAL TO ADVANCE REAL-TIME CAR-T CELL MONITORING, SUPPORTING PERSONALIZED DOSING AND TREATMENT STRATEGIES, AND CONTRIBUTING BROADLY TO CANCER IMMUNOTHERAPY, BIO-IMAGING, AND THERAPEUTIC MONITORING APPLICATIONS. $0 6/12/26