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

Overview

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.

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.