CAR-T Cell Efficacy With Molecular Imaging in Multiple Myeloma

Visualizing CAR-T Cell Therapy in Multiple Myeloma Using a BCMA-Targeted PET Probe

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-invasive CAR-T Cell Monitoring; BCMA-targeted PET Imaging; CAR-T Cell Biodistribution and Persistence; GMP-compliant Radiopharmaceutical Preparation
• Intervention / Treatment: Other: BCMA-Targeting CAR-T Cell Therapy; Device: PET/CT Imaging

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xueyan Zhou, M.D., Ph.D.; Phone Number: 15105200571; Email: zxy851107@xzhmu.edu.cn
• Study Contact Backup: Name: Jiang Cao; Phone Number: 13852432263; Email: zimu05067@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

• **Exclusion Criteria**

  1. Participation in another interventional clinical trial, concurrently or within 28 days prior to the first dose in this study. Participation in non-interventional trials is permitted.
  2. History of hypersensitivity to any component of the imaging agent or antibodies, or a known allergic predisposition.
  3. Inability to undergo PET/CT imaging, such as due to claustrophobia or emotional instability.
  4. Current use of anticoagulant therapy or anticipated requirement for such therapy during the study period.
  5. Known allergic or hypersensitivity reactions to biological products or any excipient of the 68Ga-NOTA-BCMA molecular probe.
  6. Active hepatitis B or C infection, or seropositivity for human immunodeficiency virus (HIV) antibody or Treponema pallidum antibody.
  7. Pregnancy, lactation, or intention to become pregnant during the trial period.
  8. Any other condition deemed by the investigator to render the subject unsuitable for trial participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 68Ga-NOTA-BCMA; Eligible subjects enrolled in the study will receive a predetermined dose of the 68Ga-NOTA-BCMA radiopharmaceutical preparation as part of the investigational imaging protocol.

Other: BCMA-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.; Device: PET/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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAR-T Cell Expansion and Persistence	Quantitative measurement of CAR-T copy number in peripheral blood using qPCR.	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.	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.	Day 6±2 and Day 11±2 post-CAR-T infusion.

Collaborators and Investigators

• Sponsor: Xuzhou Medical University
• Investigators: Principal Investigator: Xueyan Zhou, M.D., Ph.D., Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 17, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Estimated): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: ⁶⁸Ga-NOTA-BCMA; BCMA CAR-T cell imaging; BCMA PET tracer; Radiolabeled BCMA peptide
• Other Study ID Numbers: XYFY2025-KL519-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No