PET Imaging Study of 68Ga-NB381 in Multiple Myeloma

NCT ID: NCT06385652

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2026-12-31

Brief Summary

Multiple myeloma (MM) predominantly affects the elderly, often presenting insidiously and with a rising incidence rate. Current diagnostic methods primarily rely on invasive bone marrow biopsies, which can lead to false-negative results if the biopsy site is improperly chosen. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for this disease.

Addressing the limitations in specificity and sensitivity of traditional PET imaging agents, this project is dedicated to developing a new type of nanobody PET/CT imaging probe, 68Ga-NB381, which possesses high affinity and targets CD38. This probe, which is an intellectual property of our institution, aims to enhance the accuracy and specificity of early MM diagnosis. In terms of clinical evaluation, the project will implement a comprehensive assessment process including case selection, collection of baseline information, high-precision imaging, expert-level image interpretation, and follow-up studies, comparing directly with traditional 18F-FDG imaging to thoroughly verify the specificity and safety of 68Ga-NB381. This lays the groundwork for the clinical translation of this radiopharmaceutical in China. Furthermore, the project contributes to formulating more effective precision treatment plans based on CD38 expression levels and provides evidence for monitoring the therapeutic effects of daratumumab, a drug also targeting CD38. This makes the project of significant academic value and clinical importance, thus promoting the development of personalized treatment strategies.

Detailed Description

Multiple myeloma (MM) commonly occurs in the elderly and often remains undetected until it reaches an advanced stage. With the aging population in China, the incidence of MM is on the rise, now surpassing that of acute leukemia. Clinically, MM is characterized by bone destruction and lacks specificity; diagnosis primarily relies on bone marrow biopsies that detect an increase in clonal plasma cells, which are invasive and can yield false-negative results if the biopsy site is improperly selected. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for MM.

As the incidence of malignant tumors in China continues to increase, so does the clinical demand for radiopharmaceuticals. Addressing the limitations in the targeting of 18F-FDG in PET imaging, the development of new targeted nuclear medicine molecular probes is of significant academic value and clinical importance, particularly in monitoring the therapeutic effects of the CD38-targeted nanobody NB381, which offers unique advantages. This project uses a nanobody with high affinity for CD38 as the targeting moiety for the radiopharmaceutical, exploring the diagnostic efficiency of 68Ga-NB381 in patients with MM exhibiting high CD38 expression. This not only provides a basis for the early diagnosis of MM but also allows for the formulation of effective precision treatment strategies based on the CD38 expression profile in MM patients.

68Ga-NB381, a new CD38-targeted molecular probe labeled with 68Ga, can be used for the diagnosis and research of various malignancies expressing high levels of CD38, including MM. The probe is conjugated with 68Ga3+ using TOHP as a bifunctional chelator, with a simple labeling process that does not require purification, offering high in-vivo stability and significant radioactive accumulation in tumor sites in mouse models, resulting in superior imaging outcomes. This project will complete the automation of the 68Ga-NB381 labeling process and conduct quality control studies on the resulting radiopharmaceutical injection solution, establishing quality standards for this new PET probe and laying the foundation for its clinical translation in China. The project aims to provide 68Ga-NB381 PET/CT imaging studies to support the early diagnosis of CD38 high-expression malignancies, the formulation of treatment plans, and the assessment of therapeutic efficacy.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Head to head PET imaging comparison between 18F-FDG and 68Ga-NB381 for MM diagnosis

1. 68Ga-NB381 PET/CT Examination: The patient will be intravenously injected with prepared and quality-controlled 68Ga-NB381 (0.05-0.1 mCi/kg). Two hours post-injection, a full-body scan will be conducted using the Shanghai United Imaging uMI 780 PET/CT, covering from the top of the head to the mid-thigh. If indeterminate lesions are identified in routine imaging, delayed imaging will be performed for further evaluation. The patient should lie in a supine position and breathe calmly. Data will be reconstructed using the OSEM method to obtain coronal, sagittal, and transverse PET and PET/CT fused images.

2. 18F-FDG PET/CT Examination: Patients must fast for more than 6 hours before the examination. 18F-FDG (0.05-0.1 mCi/kg) will be administered intravenously, and one hour later. Same requirement as mentioned above.

Group Type: EXPERIMENTAL

68Ga-NB381

Intervention Type: DRUG

Lei Kang from Peking University First Hospital and Bing Jia's team from the School of Basic Medical Sciences at Peking University have developed a targeted CD38 nanobody sequence using genetic engineering technology. They have optimized its structure, functionalized it with labeling, and conducted imaging and other evaluations, ultimately producing the CD38-targeted nuclear medicine small molecule diagnostic and therapeutic agent-68Ga-labeled nanobody NB381. The post-labeling quality control of the drug meets clinical trial requirements with a radiochemical purity (PCR) greater than 98% and in vitro stability not less than 90%.

Preliminary PET imaging results of 68Ga-NB381 indicate that the nanobody is primarily concentrated in the kidneys, bladder, and MM.1S and Ramos or H929 tumors (CD38+). Additionally, the cold antibody NB381 significantly inhibits the uptake of 68Ga-NB381 in tumors, confirming the high specificity of this nanobody's binding to the CD38 protein.

Interventions

68Ga-NB381

Lei Kang from Peking University First Hospital and Bing Jia's team from the School of Basic Medical Sciences at Peking University have developed a targeted CD38 nanobody sequence using genetic engineering technology. They have optimized its structure, functionalized it with labeling, and conducted imaging and other evaluations, ultimately producing the CD38-targeted nuclear medicine small molecule diagnostic and therapeutic agent-68Ga-labeled nanobody NB381. The post-labeling quality control of the drug meets clinical trial requirements with a radiochemical purity (PCR) greater than 98% and in vitro stability not less than 90%.

Preliminary PET imaging results of 68Ga-NB381 indicate that the nanobody is primarily concentrated in the kidneys, bladder, and MM.1S and Ramos or H929 tumors (CD38+). Additionally, the cold antibody NB381 significantly inhibits the uptake of 68Ga-NB381 in tumors, confirming the high specificity of this nanobody's binding to the CD38 protein.

Intervention Type: DRUG

Other Intervention Names

18F-FDG

Eligibility Criteria

Inclusion Criteria

• Patients suspected of multiple myeloma who are scheduled to undergo bone marrow aspiration or tissue biopsy within the next 3 months; aged between 18 and 90 years; participants must fully understand and voluntarily participate in this study, and sign an informed consent form; must be able to independently comply with the examination procedures.
• Confirmed symptomatic multiple myeloma patients; aged over 18 years; participants must fully understand and voluntarily participate in this study, and sign an informed consent form; must be able to independently comply with the examination procedures.

Exclusion Criteria

• Pregnant women
• Individuals who cannot understand the examination process or are unable to cooperate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University First Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lei Kang, MD

Role: STUDY_DIRECTOR

Peking University First Hospital

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

TIANYAO Wang, PhD

Role: CONTACT

tianyao.wang@pkufh.com

+8613439014669

Lei Kang, MD

Role: CONTACT

kanglei@bjmu.edu.cn

+8613811486428

Facility Contacts

Ronghui Yu, Master

Role: primary

kyc@bjmu.edu.cn

+8613466379791

References

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Reference Type: RESULT

PMID: 8049347 (View on PubMed)

Other Identifiers

PekingUFH-MM-NB381

Identifier Type: -

Identifier Source: org_study_id