Biodistribution and dosimetry of (18)F-Meta Fluorobenzyl Guanidine (MFBG): A first-in-human PET-CT imaging study of patients with neuroendocrine malignancies

Introduction: Iodine-123-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-MFBG is a positron emission tomography (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 (five with neuroblastoma and five with paraganglioma/ pheochromocytoma) received 148-444 MBq (4-12 mCi) of (18)F-MFBG IV followed by serial whole-body imaging at 0.5-1 h, 1-2 h, and 3-4 h post-injection (p.i.). Serial blood samples (a total of 6) were also obtained starting at 5 min p.i. to as late as 4 h p.i. whole-body distribution and blood clearance data, lesion uptake, and normal tissue uptakes were determined; radiation-absorbed doses to normal organs were calculated using Organ Level INternal Dose Assessment (OLINDA). Results: No side effects were seen in any patient after (18)F-MFBG injection. Tracer distribution showed prominent activity in bloodpool, liver, and salivary glands that decreased with time. Mild uptake was seen in kidneys and spleen, which also decreased with time. Urinary excretion was prominent, with an average of 45% of the administered activity in bladder by 1 h p.i. whole-body clearance was monoexponential with mean biologic half-life (T1/2b) of 1.95 h, while blood clearance was bi-exponential with mean T1/2b of 0.3 h (58 %) for the rapid α phase and 6.1 h (42%) for the slower β phase. Urinary bladder received the highest radiation dose with a mean absorbed dose of 0.186 ± 0.195 mGy/MBq. Mean total body dose was 0.011 ± 0.011 mGy/MBq and the effective dose was 0.023± 0.012 mSv/Mbq. Both skeletal and soft tissue lesions were visualized with high contrast. The maximum standard uptake value (SUVMAX) [mean ± standard deviation (SD)] of lesions at 1-2 h p.i. was 8.6 ± 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.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Jul 13 [Epub ahead of print]

Neeta Pandit-Taskar, Pat B Zanzonico, Kevin D Staton, Jorge A Carrasquillo, Diane Reidy-Lagunes, Serge K Lyashchenko, Eva Burnazi, Hanwen Zhang, Jason S Lewis, Ronald Blasberg, Steven M Larson, Wolfgang Andreas Weber, Shakeel Modak

Memorial Sloan Kettering Cancer Center, United States.