Biodistribution and Dosimetry of 18F-Meta-Fluorobenzylguanidine: A First-in-Human PET/CT Imaging Study of Patients with Neuroendocrine Malignancies

Abstract

¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) imaging is currently a mainstay in the evaluation of many neuroendocrine tumors, especially neuroblastoma. ¹²³I-MIBG imaging has several limitations that can be overcome by the use of a PET agent. ¹⁸F-meta-fluorobenzylguanidine (¹⁸F-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 ¹⁸F-MFBG PET imaging to evaluate the safety, feasibility, pharmacokinetics, and dosimetry of ¹⁸F-MFBG in neuroendocrine tumors (NETs). Methods: Ten patients (5 with neuroblastoma and 5 with paraganglioma/pheochromocytoma) received 148-444 MBq (4-12mCi) of ¹⁸F-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 ¹⁸F-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 α phase and 6.1 h (42%) for the slower β phase. The urinary bladder received the highest radiation dose with a mean absorbed dose of 0.186 ± 0.195 mGy/MBq. The 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 SUVmax (mean ± SD ) of lesions at 1-2 h after injection was 8.6 ± 9.6. Conclusion: Preliminary data show that ¹⁸F-MFBG imaging is safe and has favorable biodistribution and kinetics with good targeting of lesions. PET imaging with ¹⁸F-MFBG allows for same-day imaging of NETs. ¹⁸F-MFBG appears highly promising for imaging of patients with NETs, especially children with neuroblastoma.

Keywords: 18F-MFBG; MIBG; dosimetry; neuroblastoma; neuroendocrine.

FIGURE 1.

Whole-body (A) and -blood (B) clearance time–activity curves. Whole-body activity showed monoexponential clearance, and blood activity showed biexponential clearance. Para = paraganglioma; Pheo = pheochromocytoma.

FIGURE 2.

Patient with metastatic pheochromocytoma. Whole-body maximum-intensity-projection scans of ¹⁸F-MFBG obtained 30–60 min after injection (A), 1–2 h after injection (B), and 3–4 h after injection (C) as against a uniform SUV scale (right bar). Lesions are distinctly seen in the liver at 1–2 h and 3–4 h after injection (B and C; arrows). Fused images show lesions more distinctly in liver (D and E; arrows). Lesion in maximum-intensity-projection image is localized to left iliac bone (F; short arrow).

FIGURE 3.

Uptake in normal organs at various scan times after injection. (A) Uptake decreases from scan 1 (0.5–1 h after injection) to scan 2 (1–2 h after injection) and scan 3 (3–4 h after injection). (B) Prominent activity is seen in liver, which decreases over time. Focal uptake posteromedially is uptake along adrenal (SUV 5.6). (C) Cardiac activity is most prominent in early images, decreasing with time; distribution is seen along the ventricular myocardium. (D) Diffuse uptake is seen along pancreas (SUV 3.5); posteromedial uptake is physiologic uptake in adrenal gland. (E) Uptake is seen in prostate (SUV 5.6).

FIGURE 4.

Patient with neuroblastoma for follow-up evaluation and possible therapy with ¹³¹I-MIBG. ¹²³I-MIBG images (A, anterior; B, posterior) show foci of suspicious activity in skull, lumbar vertebra, right and left acetabula, and right femur (black arrows). Patient underwent imaging with 162 MBq of ¹⁸F-MFBG a wk later. Whole-body maximum-intensity-projection scans with ¹⁸F-MFBG (C and D) show all lesions seen on ¹²³I-MIBG scan but with greater contrast and clarity (black arrows). In addition, several lesions are seen on ¹⁸F-MFBG scan only (red arrows) that are not visible on ¹²³I-MIBG images. For example, fused PET/CT transaxial ¹⁸F-MFBG image (F) shows intense uptake in left acetabulum (red arrow), suspicious for disease, that is not seen on ¹²³I-MIBG SPECT/CT fused transaxial image (E). Also, left iliac bone lesions are clearly avid on ¹⁸F-MFBG (H) vs. ¹²³I-MIBG imaging (G).

FIGURE 5.

Tumor–to–normal bone and soft-tissue uptake ratios at different scan times after injection of ¹⁸F-MFBG (scan 1 at 30–60 min, scan 2 at 60–120 min, and scan 3 at 180–240 min). Uptake ratios were based on mean SUVs in respective tissues of 10 patients. Numbers = number of observations (i.e., lesions); error bars = SE of mean.