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

Clinical PET Imaging Evaluation of 68Ga-BC1 Probe in Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma and Malignant Plasma Cell Neoplasms
• Intervention / Treatment: Drug: 68Ga-BC1; Drug: 18F-FDG

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Tianyao Wang, PhD; Phone Number: 9298551137; Email: tianyao.wang@pkufh.com
• Study Contact Backup: Name: Tingting Yuan, M.D.; Phone Number: 13051707479; Email: biluohtt@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 010000
      • Recruiting
      • Department of Nuclear Medicine, Peking University First Hospital
      • Contact: Tianyao Wang, Ph.D.; Phone Number: +86-010-83575252; Email: tianyao.wang@pku.edu.cn
      • Contact: Zhao Chen, M.D.; Phone Number: +86-010-83572916; Email: 19801258667@163.com
      • Principal Investigator: Tianyao Wang, Ph.D.
    • Beijing, Beijing, China, 100000
      • Enrolling by invitation
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 68Ga-BC1 PET/CT diagnosis	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.
Active Comparator: 18F-FDG PET/CT diagnosis	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MM patients will be recruited to undergo PET/CT imaging using 68Ga-NB381 and 18F-FDG to evaluate and verify that the imaging agent 68Ga-NB381 can safely and effectively identify lesions.	This study will investigate the radioactive uptake of 68Ga-BC1 in lesion sites of multiple myeloma patients and evaluate the ability of 68Ga-BC1 to detect BCMA overexpression in these patients. According to the admission and exclusion criteria, patients who meet the conditions are screened. After the patients were enrolled, baseline examination information was collected, including blood routine, blood biochemistry, tumour markers, histopathological diagnosis results, imaging diagnosis results, etc. For the Follow-up information, the patient's bone marrow aspirate or pathological tissue biopsy, laboratory test results (blood monoclonal M protein, 24-hour urine light chain, etc.), bone scintigraphy, CT or MR and other imaging examination results would be collected.	All PET/CT images will be reviewed by physicians, and a unified diagnostic opinion will be provided within 3 days after adminis. After imaging, patients will be scheduled for follow-up visits every 3 months, with a follow-up period of at least 12 months.

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Study Chair: Lei Kang, M.D., Peking University First Hospital; Study Director: Yujun Dong Dong, M.D., Peking University First Hospital; Principal Investigator: Tianyao Wang, Ph.D., 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, 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 28, 2024
• First Submitted That Met QC Criteria: November 29, 2024
• First Posted (Actual): December 4, 2024

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: multiple myeloma; Immuno-PET; molecular probe
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: PekingUFH-MM-BC1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Some representative clinical trial results will be used for publication in ICMJE journals.
• IPD Sharing Time Frame: January 2025-December 2027
• IPD Sharing Access Criteria: The ICMJE journals and their readers.
• IPD Sharing Supporting Information Type: CSR

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