A single-arm prospective phase I trial of 68Ga-PFBC01 PET/CT for multiple myeloma B cell maturation antigen imaging
Tingfei Gu, Zhao Chen, Bo Tang, Tianyao Wang, Qi Yang, Huihui Liu, Zeyin Liang, Qian Wang, Yang Zhang, Yuhua Sun, Mingyi Di, Tingting Yuan, Yongkang Qiu, Yimeng Du, Lele Song, Shengnan Wu, Wei Wang, Xiaojie Xu, Yujun Dong, Lei Kang
Tingfei Gu, Zhao Chen, Bo Tang, Tianyao Wang, Qi Yang, Huihui Liu, Zeyin Liang, Qian Wang, Yang Zhang, Yuhua Sun, Mingyi Di, Tingting Yuan, Yongkang Qiu, Yimeng Du, Lele Song, Shengnan Wu, Wei Wang, Xiaojie Xu, Yujun Dong, Lei Kang
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Clinical Research and Public Health Clinical Research Hematology Oncology

A single-arm prospective phase I trial of 68Ga-PFBC01 PET/CT for multiple myeloma B cell maturation antigen imaging

Abstract

BACKGROUND B cell maturation antigen (BCMA) is a key therapeutic target in multiple myeloma (MM), yet its whole-body in vivo distribution and role in disease assessment remain incompletely defined. We aimed to evaluate the safety, diagnostic performance, and clinical utility of a novel BCMA-targeted PET tracer, 68Ga-PFBC01, in patients with plasma cell disorders.METHODS We conducted a single-center, prospective, single-arm phase I trial (ClinicalTrials.gov NCT06717113). Fifty patients underwent 68Ga-PFBC01 PET/CT, including 40 with paired 18F-FDG PET/CT for head-to-head comparison. Primary outcomes included diagnostic performance (sensitivity, specificity, PPV, NPV, and interreader agreement). Secondary outcomes included correlations with clinical biomarkers, treatment response assessment, impact on clinical decision-making, and safety.RESULTS 68Ga-PFBC01 PET/CT demonstrated superior diagnostic performance compared with 18F-FDG PET/CT (sensitivity 96.9% versus 84.6%; specificity 71.4% versus 60.0%). Quantitative PET-derived tumor burden correlated with M protein (R = 0.325, P = 0.026), free light chains (R = 0.340–0.437, P ≤ 0.015), soluble BCMA (R = 0.433, P = 0.050), and bone marrow plasma cells (R = 0.682, P < 0.001). Imaging findings altered clinical management in multiple cases, enabling both therapy escalation and deescalation. Blood-pool uptake strongly correlated with soluble BCMA (R = 0.899, P < 0.001) and overall disease burden (R = 0.736, P < 0.001). No serious tracer-related adverse events were observed; 2 patients (4%) experienced mild events.CONCLUSION 68Ga-PFBC01 PET/CT provides biologically specific, whole-body assessment of MM, outperforming 18F-FDG and enabling integrated evaluation of tumor burden and systemic disease activity, with direct implications for clinical decision-making.TRIAL REGISTRATION ClinicalTrials.gov NCT06717113.FUNDING National Natural Science Foundation of China (82472018, 82402320), Beijing Nova Program (20240484725), National High Level Hospital Clinical Research Funding (Interdisciplinary Research Project of Peking University First Hospital, 2024IR07, Scientific and Technological Achievements Transformation Incubation Guidance Fund Project of Peking University First Hospital, 2025CX38, 2024CX18). Research Achievement Transformation Project of Peking University First Hospital, 2025ZH02), Clinical Medicine Plus X - Young Scholars Project of Peking University, the Fundamental Research Funds for the Central Universities (PKU2026PKULCXQ038).

Authors

Tingfei Gu, Zhao Chen, Bo Tang, Tianyao Wang, Qi Yang, Huihui Liu, Zeyin Liang, Qian Wang, Yang Zhang, Yuhua Sun, Mingyi Di, Tingting Yuan, Yongkang Qiu, Yimeng Du, Lele Song, Shengnan Wu, Wei Wang, Xiaojie Xu, Yujun Dong, Lei Kang

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Figure 1

Preparation and preclinical characterization of 68Ga-PFBC01 for PET/CT imaging.

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Preparation and preclinical characterization of 68Ga-PFBC01 for PET/CT i...
(A) Schematic illustration of the 68Ga-PFBC01 PET/CT probe for the precise diagnosis of MM. (B) SDS-PAGE confirmed greater than 90% purity of the sdAb following Ni2+ affinity purification. (C) ELISA assay confirmed the high binding affinity of the PFBC01 for the BCMA protein. (D) Bio-layer interferometry showed strong binding affinity between PFBC01 and BCMA protein. (E) Cell uptake and blocking assays demonstrated specific binding in H929 cells compared with blocking and K562 cells (n = 3). (F) Flow cytometry analysis showing rightward fluorescence shift in BCMA-positive H929 and MM.1S cells. (G) TLC analysis showed high radiochemical purity in PBS and FBS (n = 3). (H) Maximum intensity projection (MIP) PET images of subcutaneous tumor models. (I) Quantitative Region of Interest (ROI) analysis of PET imaging in subcutaneous tumor models (n = 4 for H929; n = 7 for H929 blocking; n = 4 for K562). (J) Biodistribution study at 1 hour after injection corroborating the PET findings of subcutaneous tumor models. (K) Representative PET images (coronal, axial, and sagittal views) of an orthotopic MM.1S model. The probe efficiently accumulated in various tumor foci (white arrows), clearly delineating even small lesions. (L) Quantitative PET analysis of the orthotopic model (n = 3). (M) Biodistribution analysis at 1 hour after injection of the orthotopic model (n = 3). (N) MIP PET images for monitoring therapy response (DVD regimen). A reduction in tumor uptake was evident on day 5 after treatment, with a further decrease observed on day 10. (O) Quantitative PET analysis of therapy response (n = 3). (P) Histopathology and IHC confirmed strong BCMA expressions in H929 and MM.1S tumors, but minimal staining in K562 tumors. (Q) Dynamic PET imaging following intravenous injection of the probe in a healthy cynomolgus monkey. (R) Quantitative PET analysis in healthy cynomolgus monkeys showed rapid clearance and predominant renal excretion of the tracer (n = 3).