⁶⁸Ga-NOTA-BCMA is a novel, targeted PET tracer under clinical investigation. It is designed to provide a non-invasive method for monitoring the biodistribution and persistence of BCMA CAR-T cells in patients. Preclinical data robustly support its specific binding, favorable pharmacokinetics, and excellent safety profile, warranting its advancement into clinical studies.
⁶⁸Ga-NOTA-BCMA is an investigational PET radiopharmaceutical designed for targeted in vivo tracking of BCMA-directed CAR-T cells. Its molecular design incorporates a BCMA-derived peptide, specific for the CAR's scFv, conjugated to the ⁶⁸Ga-chelator NOTA. Preclinical data confirm high target affinity, rapid renal clearance (t₁/₂α=3.30 min, t₁/₂β=33.27 min), and an excellent safety profile with no drug-related toxicities in murine models. The agent is administered as a single IV bolus (4 mCi/80 μg) and must be used within 4 hours of GMP-compliant, on-site radiolabeling.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Patient T-cells are harvested and genetically engineered to express chimeric antigen receptors (CARs) targeting B-cell maturation antigen (BCMA). These modified CAR-T cells specifically recognize and eliminate multiple myeloma cells expressing BCMA. Following reinfusion, the CAR-T cells undergo antigen-stimulated proliferation, establishing sustained antitumor immune activity.
A low-dose PET/CT scan will be performed 60 minutes post-administration of the agent. Low-dose CT is only utilized for anatomic localization and PET attenuation correction, and the radiation dose involved is substantially lower than that of conventional CT.
Biodistribution of 68Ga-NOTA-BCMA
Assessment of tracer uptake in tumor and normal tissues (e.g., brain, liver, heart) by measuring Standardized Uptake Values (SUV) on low-dose PET/CT scans.
Time frame: Baseline (pre-CAR-T), and at Day 6±2, Day 11±2, Day 21±2 post-CAR-T infusion (Scan at 60 minutes post-injection). For the first 3 subjects, additional scans at 30 and 120 minutes post-injection will be performed at baseline.
Pharmacokinetic assessment of 68Ga-NOTA-BCMA: measurement of elimination half-life (t1/2)
Measure the elimination half-lives of radioactive concentrations in whole blood and plasma at multiple time points to characterize the clearance kinetics of the tracer.
Time frame: Baseline: pre-injection, and at 2, 5, 10, 15, 30, 60, 90, 120 minutes post-injection of 68Ga-NOTA-BCMA. (May be omitted for subsequent subjects based on results from the first 5 subjects).
CAR-T Cell Expansion and Persistence
Quantitative measurement of CAR-T copy number in peripheral blood using qPCR.
Time frame: Day 6±2 and Day 11±2 post-CAR-T infusion.
Safety and Tolerability of 68Ga-NOTA-BCMA
The number of participants with adverse events is assessed via the NCI Common Terminology Criteria for Adverse Events (CTCAE) V5.0. The number of participants with abnormal vital signs is assessed using electronic thermometers, electronic sphygmomanometers, electronic monitors (for heart rate), and manual chest rise counting. The number of participants with abnormal physical examination findings is assessed in accordance with standard clinical protocols. The number of participants with laboratory abnormalities (including hematology, urinalysis, coagulation, and blood biochemistry) is assessed using automated analyzers (for hematology, coagulation, and blood biochemistry), dry chemistry analyzers, and sediment microscopes (for urinalysis). The number of participants with abnormal electrocardiogram (ECG) findings is assessed via 12-lead electrocardiograph testing.
Time frame: Vital signs: pre-injection and 2 hours (±1h) post-injection of 68Ga-NOTA-BCMA. Other safety assessments: throughout the study, with a follow-up at Day 28±2 after the last tracer dose.
CAR-T Cell Immunophenotyping
Characterization of CAR-T cell populations in peripheral blood using flow cytometry.
Time frame: Day 6±2 and Day 11±2 post-CAR-T infusion.
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