SUV normalisation and reference tissue selection for [¹⁸F]mFBG PET-CT in paediatric and adult patients

Purpose: Meta-[¹⁸F]fluorobenzylguanidine ([¹⁸F]mFBG) PET-CT is a novel imaging modality for norepinephrine transporter-expressing tumours, such as neuroblastoma and phaeochromocytoma, enabling quantitative assessment and improved diagnostic accuracy compared to meta-[¹²³I]iodobenzylguanidine ([¹²³I]mIBG) scintigraphy. This study aims to: 1) Identify the optimal standardised uptake value (SUV) normalisation method: body weight (BW) or lean body mass (LBM); 2) Determine the most stable reference tissue with SUV uptake below pathological levels. Methods: We analysed 63 [¹⁸F]mFBG PET-CTs from 35 patients (20 paediatric neuroblastoma, 15 adult phaeochromocytoma). SUV_mean was measured in the liver, blood pool, bone marrow, and muscle, normalised using BW (SUVBW), LBM via James (SUVLBMJames), and LBM via Janmahasatian (SUVLBMJanma). Variability of SUVs and their correlation with weight were assessed. Results: LBM-based normalisation reduced SUV variability compared to BW-based normalisation. Bone marrow demonstrated the lowest variability and least weight dependency (r² 0.45 for SUVBW versus 0.31 for SUVLBMJanma). The liver had the highest SUVs, increasing the risk of false negatives if used as reference tissue, while the blood pool had the lowest SUVs, raising the risk of false positives. Muscle showed relatively stable SUVs with increasing weight but higher variability than bone marrow. Conclusion: LBM-based SUV normalisation reduces weight dependency for [¹⁸F]mFBG PET-CT. Bone marrow is the most reliable reference tissue due to its low variability and balanced SUVs, while muscle may serve as an alternative if diffuse bone marrow uptake is present. These findings support standardising LBM-adjusted SUV methods and using bone marrow as the primary reference tissue to enhance diagnostic accuracy. Clinical trial registration: EudraCT Number: 2019–003713-33; EU Clinical Trials Number: 2024–513622-35–00.