BCMA-targeted PET Imaging, CAR-T Cell Biodistribution and Persistence, GMP-compliant Radiopharmaceutical Preparation, Non-invasive CAR-T Cell Monitoring
Conditions
Keywords
⁶⁸Ga-NOTA-BCMA, BCMA CAR-T cell imaging, BCMA PET tracer, Radiolabeled BCMA peptide
Brief summary
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.
Detailed description
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.
Interventions
OTHERBCMA-Targeting CAR-T Cell Therapy
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.
DEVICEPET/CT Imaging
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.
Sponsors
Xuzhou Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* \*\*Inclusion Criteria\*\* 1. Subjects must voluntarily sign the informed consent form and be able to complete the trial per the protocol requirements. 2. Age 18 years or older, regardless of gender. 3. Diagnosed with multiple myeloma and scheduled to receive anti-BCMA CAR-T cell therapy. 4. ECOG performance status of 0-2; with a life expectancy of not less than 3 months. 5. Female subjects of childbearing potential must have a negative serum pregnancy test prior to enrollment. 6. For female subjects of childbearing potential or male subjects with partners of childbearing potential, agreement to remain abstinent or use one or more forms of contraception with a failure rate of \<1% per year during the study period and for at least one year after the study completion.
Exclusion criteria
* \*\*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biodistribution of 68Ga-NOTA-BCMA | 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. | 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. |
| Pharmacokinetic assessment of 68Ga-NOTA-BCMA: measurement of elimination half-life (t1/2) | 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). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAR-T Cell Expansion and Persistence | Day 6±2 and Day 11±2 post-CAR-T infusion. | Quantitative measurement of CAR-T copy number in peripheral blood using qPCR. |
| Safety and Tolerability of 68Ga-NOTA-BCMA | 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. | 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. |
| CAR-T Cell Immunophenotyping | Day 6±2 and Day 11±2 post-CAR-T infusion. | Characterization of CAR-T cell populations in peripheral blood using flow cytometry. |
Contacts
Primary ContactXueyan Zhou, M.D., Ph.D.
Backup ContactJiang Cao
Outcome results
None listed