PET Imaging Study of 68Ga-NB381 in Multiple Myeloma

Clinical PET Imaging Evaluation of 68Ga-NB381 Probe in Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: 68Ga-NB381

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: TIANYAO Wang, PhD; Phone Number: +8613439014669; Email: tianyao.wang@pkufh.com
• Study Contact Backup: Name: Lei Kang, MD; Phone Number: +8613811486428; Email: kanglei@bjmu.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Recruiting
      • Peking University First Hospital
      • Contact: Ronghui Yu, Master; Phone Number: +8613466379791; Email: kyc@bjmu.edu.cn
      • Principal Investigator: Lei Kang, MD
      • Principal Investigator: TIANYAO Wang, PhD
      • Sub-Investigator: Yongkang Qiu, Master
      • Sub-Investigator: Zhenghao Tong, MD

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: 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.; Other Names: 18F-FDG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specificity and Binding Efficiency of 68Ga-NB381 in CD38 Positive Tumors	Evaluate the specificity and binding efficiency of 68Ga-labeled NB381 nanobody in targeting CD38 positive tumors using PET imaging. The measure involves comparing the uptake of 68Ga-NB381 in CD38 positive tumors to non-target areas and assessing the ability of cold antibody NB381 to inhibit this uptake, thus confirming the high specificity of the nanobody for CD38 protein.	For a single patient, imaging and analysis will be conducted within 24 hours post-injection; follow-up assessments for stability and biodistribution will be conducted at 1 week post-injection.
Baseline Pathological Characteristics: Histopathology, Flow Cytometry, and Immunohistochemistry	Baseline bone marrow pathological assessments will be performed, including: (1) histopathological evaluation of plasma cell infiltration; (2) flow cytometry to quantify the proportion of malignant plasma cells and CD38-positive cells; and (3) immunohistochemical profiling for relevant markers (e.g., CD138, κ/λ light chain restriction). Results will be summarized descriptively for baseline disease characterization.	Baseline (within 28 days prior to first dose of study intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Disease Characterization: International Staging System (ISS) Stage and Immunofixation Electrophoresis (IFE) Type	Baseline disease characteristics of enrolled participants will be documented, including: (1) International Staging System (ISS) stage (I, II, or III), determined by serum β2-microglobulin and albumin levels per International Myeloma Working Group (IMWG) criteria; and (2) Immunofixation electrophoresis (IFE) type identifying the monoclonal protein isotype (e.g., IgG κ, IgG λ, IgA κ, IgA λ, IgD, free light chain-only, or non-secretory disease). These baseline stratification factors will be summarized descriptively and may be used for pre-specified subgroup analyses to evaluate treatment effect consistency across disease risk profiles.	Baseline (within 28 days prior to first dose of study intervention)
Baseline Laboratory Assessments: Hematology, Clinical Chemistry, and Myeloma-Specific Biomarkers	Baseline laboratory parameters will be collected, including complete blood count, clinical chemistry (renal/hepatic function, electrolytes, LDH), serum immunoglobulins, serum and urine M-protein quantification, serum free light chains with κ/λ ratio, and urine immunofixation electrophoresis. Results will be summarized descriptively and may be used for baseline characterization and subgroup analyses.	Baseline (within 28 days prior to first dose of study intervention)
Treatment Response Assessment per IMWG Criteria	Treatment response will be evaluated according to the International Myeloma Working Group (IMWG) consensus criteria, categorizing disease status as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), or progressive disease (PD). Results will be used to assess preliminary antitumor efficacy.	End of Cycle 2 (approximately 2 months after first dose) and End of Cycle 4 (approximately 4 months after first dose)

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Study Director: Lei Kang, MD, Peking University First Hospital

Publications and helpful links

General Publications

• Kang L, Jiang D, England CG, Barnhart TE, Yu B, Rosenkrans ZT, Wang R, Engle JW, Xu X, Huang P, Cai W. ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled daratumumab. Eur J Nucl Med Mol Imaging. 2018 Jul;45(8):1372-1381. doi: 10.1007/s00259-018-3941-3. Epub 2018 Feb 15.
• Kang L, Li C, Yang Q, Sutherlin L, Wang L, Chen Z, Becker KV, Huo N, Qiu Y, Engle JW, Wang R, He C, Jiang D, Xu X, Cai W. 64Cu-labeled daratumumab F(ab')2 fragment enables early visualization of CD38-positive lymphoma. Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1470-1481. doi: 10.1007/s00259-021-05593-9. Epub 2021 Oct 22.
• Kang L, Li C, Rosenkrans ZT, Huo N, Chen Z, Ehlerding EB, Huo Y, Ferreira CA, Barnhart TE, Engle JW, Wang R, Jiang D, Xu X, Cai W. CD38-Targeted Theranostics of Lymphoma with 89Zr/177Lu-Labeled Daratumumab. Adv Sci (Weinh). 2021 Mar 15;8(10):2001879. doi: 10.1002/advs.202001879. eCollection 2021 May.
• Kang L, Li C, Rosenkrans ZT, Engle JW, Wang R, Jiang D, Xu X, Cai W. Noninvasive Evaluation of CD20 Expression Using 64Cu-Labeled F(ab')2 Fragments of Obinutuzumab in Lymphoma. J Nucl Med. 2021 Mar;62(3):372-378. doi: 10.2967/jnumed.120.246595. Epub 2020 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2024
• Primary Completion (Actual): June 3, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Carbohydrates; Deoxyglucose; Deoxy Sugars; Fluorodeoxyglucose F18
• Other Study ID Numbers: PekingUFH-MM-NB381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All case data are anonymized before data analysis; all case files and imaging data are stored in a specialized database, which only the principal investigator is authorized to access and read; all researchers must not disclose any information about any patient.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No