A Molecular Probe Targeting BCMA for the Clinical Diagnosis of Multiple Myeloma

NCT ID: NCT06717113

Last Updated: 2025-06-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-15
• Study Completion Date: 2028-12-31

Brief Summary

Multiple Myeloma (MM), the second most common hematological malignancy, continues to pose challenges in precise clinical identification. As a potential solution, nuclear medicine immuno-PET imaging has emerged as a promising approach. However, traditional full-length antibody probes suffer from delayed tumor uptake peaks and low target-to-background ratios, limiting their clinical utility. In our study, a peptide or nanobody targeting BCMA was developed by computer-aided designing, which was subsequently radiolabeled with 68Ga to create a novel molecular probe, 68Ga-MM-BC1. This research aims to overcome the diagnostic limitations of MM and may also offer valuable insights for molecular-targeted imaging in other malignant tumors.

Detailed Description

Multiple Myeloma (MM) predominantly affects the elderly and often presents insidiously, with most patients being diagnosed at an advanced stage. As China's population ages, the incidence of MM is increasing, now surpassing that of acute leukemia. The primary clinical manifestation is bone destruction, which lacks specificity. Diagnosis primarily relies on invasive bone marrow biopsies to detect clonal plasma cell proliferation. However, improper selection of the biopsy site can lead to false-negative results. BCMA is highly expressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for this disease.

With the rising incidence of malignant tumors in China, there is an increasing demand for radiopharmaceuticals in clinical practice. Given the limitations of 18F-FDG in PET imaging, particularly regarding specificity, the development of novel targeted nuclear medicine molecular probes holds significant academic and clinical value. This is especially true for monitoring the therapeutic effects of peptide or nanobody-based treatments targeting BCMA, which offers distinct advantages. This project focuses on utilizing a peptide or nanobody with high affinity for BCMA as the targeting group for radiopharmaceuticals, exploring the diagnostic efficacy of 68Ga-BC1 in MM patients with high BCMA expression. This approach not only aids in the early diagnosis of MM but also helps tailor effective precision treatments for patients based on their BCMA expression levels.

68Ga-BC1, a novel BCMA-targeting molecular probe labeled with 68Ga, has potential applications in the diagnosis and research of various BCMA-expressing malignancies, including MM. 68Ga-BC1 is synthesized using THP as a bifunctional chelator to coordinate with 68Ga^3+, and the labelling process is simple, allowing for direct use without purification. It demonstrates high in vivo stability and significant tumor uptake in tumor-bearing mice, with superior imaging performance. In this project, the automated labelling process of 68Ga-BC1 will be studied, and quality control measures for the resulting radiopharmaceutical injection will be established. A quality standard for this new PET probe will be set, laying the groundwork for the clinical translation of this drug within China. This study aims to provide valuable data on 68Ga-BC1 PET/CT imaging, offering insights for the early diagnosis, treatment planning, and efficacy evaluation of patients with BCMA-expressing malignancies.

Conditions

Multiple Myeloma and Malignant Plasma Cell Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

68Ga-BC1 PET/CT diagnosis

Group Type: EXPERIMENTAL

68Ga-BC1

Intervention Type: DRUG

The prepared and quality-controlled 68Ga-BC1 (0.05-0.1 mCi/kg) will be intravenously injected into the patient. Two hours after the injection, whole-body imaging will be performed using a Shanghai United Imaging uMI 780 PET/CT scanner, covering the region from the top of the head to the mid-thigh. If any indeterminate lesions are found during the routine imaging, delayed imaging will be performed for further differentiation. The patient will lie supine and breathe calmly during the procedure. After image acquisition, the data will be reconstructed using the OSEM method to generate coronal, sagittal, transverse, and PET/CT fusion images.

18F-FDG PET/CT diagnosis

Group Type: ACTIVE_COMPARATOR

18F-FDG

Intervention Type: DRUG

Prior to the examination, patients will be required to fast for at least 6 hours. 18F-FDG (0.05-0.1 mCi/kg) will be intravenously injected, and one hour after the injection, head and torso imaging will be performed using a Shanghai United Imaging uMI 780 PET/CT scanner, covering the region from the top of the head to the upper third of the thigh. The patient will lie supine and breathe calmly during the procedure. After image acquisition, the data will be reconstructed using the OSEM method to generate coronal, sagittal, transverse, and PET/CT fusion images.

Interventions

18F-FDG

Prior to the examination, patients will be required to fast for at least 6 hours. 18F-FDG (0.05-0.1 mCi/kg) will be intravenously injected, and one hour after the injection, head and torso imaging will be performed using a Shanghai United Imaging uMI 780 PET/CT scanner, covering the region from the top of the head to the upper third of the thigh. The patient will lie supine and breathe calmly during the procedure. After image acquisition, the data will be reconstructed using the OSEM method to generate coronal, sagittal, transverse, and PET/CT fusion images.

Intervention Type: DRUG

68Ga-BC1

The prepared and quality-controlled 68Ga-BC1 (0.05-0.1 mCi/kg) will be intravenously injected into the patient. Two hours after the injection, whole-body imaging will be performed using a Shanghai United Imaging uMI 780 PET/CT scanner, covering the region from the top of the head to the mid-thigh. If any indeterminate lesions are found during the routine imaging, delayed imaging will be performed for further differentiation. The patient will lie supine and breathe calmly during the procedure. After image acquisition, the data will be reconstructed using the OSEM method to generate coronal, sagittal, transverse, and PET/CT fusion images.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Suspected multiple myeloma patients scheduled for bone marrow aspiration or tissue biopsy within the past 3 months; able to fully understand and voluntarily participate in the study, with signed informed consent; able to cooperate with the examination.
• Diagnosed symptomatic multiple myeloma patients; able to fully understand and voluntarily participate in the study, with signed informed consent; able to cooperate with the examination.

Exclusion Criteria

• Pregnant women; individuals unable to understand the examination process or who are unable to cooperate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Peking University First Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tianyao Wang

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lei Kang, M.D.

Role: STUDY_CHAIR

Peking University First Hospital

Yujun Dong Dong, M.D.

Role: STUDY_DIRECTOR

Peking University First Hospital

Tianyao Wang, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Peking University First Hospital

Locations

Department of Nuclear Medicine, Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status: ENROLLING_BY_INVITATION

Countries

China

Central Contacts

Tianyao Wang, PhD

Role: CONTACT

tianyao.wang@pkufh.com

9298551137

Tingting Yuan, M.D.

Role: CONTACT

biluohtt@163.com

13051707479

Facility Contacts

Tianyao Wang, Ph.D.

Role: primary

tianyao.wang@pku.edu.cn

+86-010-83575252

Zhao Chen, M.D.

Role: backup

19801258667@163.com

+86-010-83572916

References

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.

Reference Type: BACKGROUND

PMID: 29450576 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32826320 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34677626 (View on PubMed)

Other Identifiers

PekingUFH-MM-BC1

Identifier Type: -

Identifier Source: org_study_id