hNET-targeted [¹⁸F]MFBG PET as baseline functional imaging in newly diagnosed neuroblastoma

[¹⁸F]meta-fluorobenzylguanidine ([¹⁸F]MFBG) is an human norepinephrine transporter (hNET)-targeted PET tracer that has shown superior lesion detection than [¹²³I]MIBG SPECT in patients with relapsed or refractory neuroblastoma. Its value in newly diagnosed patients, however, has not been well established. We therefore performed this study to evaluate the additional staging information of [¹⁸F]MFBG beyond comprehensive anatomic imaging and assessed its agreement with [¹⁸F]FDG PET at baseline.

We prospectively enrolled consecutive children with newly diagnosed neuroblastoma. All patients underwent baseline [¹⁸F]MFBG PET and comprehensive anatomic imaging, including contrast-enhanced CT and/ or MRI from the neck to the pelvis and whole-body ultrasonography. The imaging studies were interpreted independently, and lesion distribution and International Neuroblastoma Risk Classification (INRG) stage were recorded. A subgroup also underwent paired [¹⁸F]FDG PET for functional comparison. Paired detection rates were compared using the McNemar test. Intermodality concordance was evaluated using Cohen κ statistics, and Curie scores were compared using Wilcoxon signed-rank tests.

Forty patients (median age, 23.5 months) were analyzed. The primary tumors were mainly located in the abdomen or pelvis (36/40, 90%), with corresponding imaging findings including contrast-enhanced abdominopelvic CT and MRI, non-contrast cervicothoracic CT, and whole-body ultrasonography. [¹⁸F]MFBG PET identified bone marrow metastases more frequently than anatomic imaging (65% vs. 32.5%, P = 0.001; κ = 0.41), leading to stage reclassification in 20% of cases and treatment modification in 10% based on tumor-board review. Even within overlapping fields of view (neck to proximal femur), [¹⁸F]MFBG maintained superior bone marrow detection rates (55% vs. 32.5%, P = 0.004; κ = 0.56). Among the patients initially classified as L2, half were upstaged based on hNET-targeted PET findings. In the paired [¹⁸F]FDG PET subset (n = 26), the patient-level INRG stage was fully concordant between modalities. However, lesion-level analysis revealed a higher bone marrow disease burden on [¹⁸F]MFBG (191 vs. 140, P = 0.002), while FDG detected 13% additional nodal lesions in five patients.

In newly diagnosed neuroblastoma, hNET-targeted [¹⁸F]MFBG PET detected clinically relevant bone marrow involvement not identified by comprehensive anatomic imaging, resulting in stage reclassification and treatment modification in a subset of patients. Paired [¹⁸F]FDG PET demonstrated patient-level stage concordance with lesion-level heterogeneity.