Clinical nuclear medicine | 2025 | Jiang ZP, Shan HM, Zhu HY, Cheng Y
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[Indexed for MEDLINE] Conflict of interest statement: Conflicts of interest and sources of funding: This work was supported by the National Natural Science Foundation of China-Youth Science Foundation (82302259) and the Guangdong Basic and Applied Basic Research Foundation Natural Science Fund (2025A1515011918). The authors declare no competing interests. 16. Eur J Nucl Med Mol Imaging. 2025 Jan;52(2):599-610. doi: 10.1007/s00259-024-06907-3. Epub 2024 Sep 11. Discovery of a highly specific radiolabeled antibody targeting B-cell maturation antigen: Applications in PET imaging of multiple myeloma. Ma J(#)(1), Zhang S(#)(2), Yang N(3), Shang J(1), Gao X(2), Chen J(4), Wei H(1), Li Y(4), Zeng H(3), Xu H(1), Wang J(5)(6), Liang SH(4), Wang R(7), Hu K(8), Wang L(9)(10). Author information: (1)Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine, & Key Laboratory of Basic and Translational Research On Radiopharmaceuticals, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. (2)State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. (3)Department of Hematology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. (4)Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Rd, Atlanta, GA, 30322, USA. (5)Department of Pharmacy, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. (6)The Guangzhou Key Laboratory of Basic and Translational Research On Chronic Disease, Guangzhou, 510630, China. (7)State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. wangrui@lzu.edu.cn. (8)State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. hukuan@imm.ac.cn. (9)Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine, & Key Laboratory of Basic and Translational Research On Radiopharmaceuticals, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. l_wang1009@foxmail.com. (10)The Guangzhou Key Laboratory of Basic and Translational Research On Chronic Disease, Guangzhou, 510630, China. l_wang1009@foxmail.com. (#)Contributed equally PURPOSE: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM. EXPERIMENTAL DESIGN: Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential. RESULTS: The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P
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