123 I-meta-iodobenzylguanidine ( 123 I-MIBG) imaging is currently a mainstay in the evaluation of many neuroendocrine tumors, especially neuroblastoma. 123 I-MIBG imaging has several limitations that can be overcome by the use of a PET agent. 18 F-meta-fluorobenzylguanidine ( 18 F-MFBG) is a PET analog of MIBG that may allow for single-day, high-resolution quantitative imaging. We conducted a first-in-human study of 18 F-MFBG PET imaging to evaluate the safety, feasibility, pharmacokinetics, and dosimetry of 18 F-MFBG in neuroendocrine tumors (NETs). Methods: Ten patients (5 with neuroblastoma and 5 with paraganglioma/pheochromocytoma) received 148–444 MBq (4–12mCi) of 18 F-MFBG intravenously followed by serial whole-body imaging at 0.5–1, 1–2, and 3–4 after injection. Serial blood samples (a total of 6) were also obtained starting at 5 min after injection to as late as 4 h after injection; whole-body distribution and blood clearance data, lesion uptake, and normal-tissue uptake were determined, and radiation-absorbed doses to normal organs were calculated using OLINDA. Results: No side effects were seen in any patient after 18 F-MFBG injection. Tracer distribution showed prominent activity in the blood pool, liver, and salivary glands that decreased with time. Mild uptake was seen in the kidneys and spleen, which also decreased with time. Urinary excretion was prominent, with an average of 45% of the administered activity in the bladder by 1 h after injection; whole-body clearance was monoexponential, with a mean biologic half-life of 1.95 h, whereas blood clearance was biexponential, with a mean biologic half-life of 0.3 h (58%) for the rapid a phase and 6.1 h (42%) for the slower b phase. The urinary bladder received the highest radiation dose with a mean absorbed dose of 0.186 6 0.195 mGy/MBq. The mean total-body dose was 0.011 6 0.011 mGy/MBq, and the effective dose was 0.023 6 0.012 mSv/MBq. Both skeletal and soft-tissue lesions were visualized with high contrast. The SUVmax (mean 6 SD) of lesions at 1–2 h after injection was 8.6 6 9.6. Conclusion: Preliminary data show that 18 F-MFBG imaging is safe and has favorable biodistribution and kinetics with good targeting of lesions. PET imaging with 18 F-MFBG allows for same-day imaging of NETs. 18 F-MFBG appears highly promising for imaging of patients with NETs, especially children with neuroblastoma.