The use of an 18F-labeled radiopharmaceutical for positron emission tomography (PET) imaging of sympathetic neuronal activity has a tremendous clinical impact because it circumvents the substantial drawbacks of the prototypical imaging agent, 123I-metaiodobenzylguanidine (MIBG). We describe a 14-year-old male patient who had neuroblastoma and underwent 18F-fluoropropylbenzylguanidine (FPBG) PET/computed tomography (CT). We compared the findings of 18F-FPBG PET/CT with those of 123I-MIBG γ scintigraphy. 18F-FPBG PET/CT readily demonstrated a focal lesion in the left tibia, but the lesion was not seen using 123I-MIBG scintigraphy. Surgical resection proved the presence of a neuroblastoma lesion in the left tibia. To the best of our knowledge, our study was the first to use an 18F-labeled radiopharmaceutical for evaluating sympathetic neuronal activity in neuroblastoma. We suggest that 18F-FPBG is a promising PET agent for imaging sympathetic neuronal activity in neuroblastoma.
- CT —
- computed tomography
- FPBG —
- MIBG —
- PET —
- positron emission tomography
- SUV —
- standardized uptake value
Several nuclear imaging agents have been used to study sympathetic neuronal activity. 123I- or 131I-labeled metaiodobenzylguanidine (MIBG) has been widely used in the management of tumors originating from sympathetic neurons, such as neuroblastoma or pheochromocytoma.1–4 Cardiac sympathetic derangement in heart failure has also been successfully investigated by using 123I-MIBG γ scintigraphy.5,6 Regarding positron emission tomography (PET), 11C-labeled radiopharmaceuticals such as 11C-hydroxyephedrine,7 11C-phenylephrine,8 and 11C-epinephrine9 have been used in many clinical studies. However, 11C-labeled PET agents are not widely used because 11C has a relatively short half-life (20.4 minutes), requiring an in-house cyclotron and a complicated radiochemical labeling procedure.
To fully exploit the capability of PET, 18F-labeled agents are ideal because they have a longer half-life (110 minutes), enabling dissemination to other institutes and a stable radiochemical labeling process. We previously reported the facile synthetic process of 18F-labeled fluoropropylbenzylguanidine (FPBG) as a PET agent for imaging sympathetic neuronal activity.10 In the current case, we report on 18F-FPBG uptake by a neuroblastoma lesion that did not show any abnormal 123I-MIBG uptake and was pathologically proved to be recurrent.
We encountered a case of a 14-year-old boy who had neuroblastoma and had experienced relapse twice. Medical history revealed that at 3 years of age, he had a left adrenal neuroblastoma that was surgically resected. At the initial presentation, a bone marrow biopsy was positive for neuroblastoma but 99mTc-methylene diphosphonate bone scintigraphy was negative. The first relapse was observed at age 6 years. It occurred in multiple bones on both sides of the ilea, acetabula, and femora, as seen on MRI, and was confirmed by bone marrow biopsy. The second relapse occurred at the right maxillary sinus at age 11 years. γ-Knife surgery, systemic chemotherapy (carboplatin, etoposide, and cyclophosphamide), and isotretinoin administration were undertaken to effectively control the second recurrence. At age 14 years, he had a dull pain in the left lower extremity. MRI was subsequently performed, revealing a lesion in the left tibia. For the characterization of the lesion, we planned to compare 123I-MIBG γ scintigraphy findings with those of 18F-FPBG PET/computed tomography (CT) in this patient. The institutional ethical review board approved the study (B-1402/237-004), and the patient and his mother provided informed consent.
123I-MIBG γ scintigraphy was first performed as a reference standard. The patient was not given any medication, such as tricyclic anti-depressants, α blockers, and β agonists that could inhibit 123I-MIBG uptake by the tumor during scintigraphy. Lugol’s solution (0.1 mL orally 3 times daily for 2 weeks) was applied to protect the thyroid. The injected dose of 123I-MIBG (MIBG [123I], KIRAMS, Korea) was 148 MBq (4 mCi). Using a dual-head γ camera (Forte, ADAC-Philips, Holt, MO, USA), 4- and 24-hour scintigrams were obtained; no abnormal uptake was observed, even in the left tibial area (Fig 1). Single photon emission CT images of the lower extremity area at 4 and 24 hours were obtained immediately after the respective planar image acquisitions; no abnormal uptake of 123I-MIBG was identified (data not shown). 18F-FPBG PET/CT was performed on the second day of the 123I-MIBG study. After 24 hours’ 123I-MIBG image acquisition, 207.2 MBq (5.6 mCi) of 18F-FPBG was immediately injected intravenously. Whole body PET/CT images were acquired using a PET/CT scanner (DVCT, GE Healthcare, Milwaukee, WI) at 30 minutes, 1 hour, and 2 hours post injection. High uptake of 18F-FPBG was observed in the liver and small intestine, which gradually decreased from 30 minutes to 2 hours post injection. Moderate 18F-FPBG uptake was noticed at the lacrimal and salivary glands. Cardiac uptake of 18F-FPBG was not prominent compared with that of the 123I-MIBG scintigraphy. However, growth plate uptake was greater in 18F-FPBG PET than in 123I-MIBG scintigraphy. 18F-FPBG uptake was readily observed in the left tibial lesion, particularly at 2 hours, and this uptake matched with the gadolinium-diethylenetriaminepentaacetic acid enhanced lesion observed on T1-weighted MRI (Fig 2). The degree of 18F-FPBG uptake was quantified by using the established method for calculating standardized uptake value (SUV): SUV = (decay-corrected radioactivity in a lesion) × (body weight) / (injected radioactivity). The maximum SUVs and average SUVs were derived from volume-of-interest analysis over multiple organs and are shown in Table 1.
Two months later, a tissue biopsy over the left tibia revealed histologic features of metastatic neuroblastoma (Fig 3).
In a preclinical study, 18F-FPBG, a derivative of fluoroalkylbenzylguanidine, was reported to have pharmacologic characteristics similar to those of 123I-MIBG.10 In this study, we tested the diagnostic usability of 18F-FPBG in imaging sympathetic neuronal activity in a 14-year-old boy who had neuroblastoma. 18F-FPBG PET/CT was more sensitive for detecting sympathetic neuronal activity than 123I-MIBG γ scintigraphy. 18F-FPBG uptake was also enhanced in other organs, such as the liver, small intestine, and cartilage growth plate (Fig 2 and Table 1). The elevated hepatic uptake of 18F-FPBG is not inconsistent with that of 123I-MIBG. The reasons 18F-FPBG showed the greater affinity for small intestine and cartilage growth plate compared with 123I-MIBG were not clearly addressed in the current study. However, because 123I-MIBG scintigraphy is considered as the reference standard for evaluating tumors originating from sympathetic neurons,1 our result will have a tremendous clinical impact on the detection and diagnosis of neuroblastoma. First, quantitative evaluation of sympathetic neuronal activity was successfully performed using 18F-FPBG PET/CT, which could not be achieved using 123I-MIBG γ scintigraphy. Because the SUV is widely used for quantifying glucose metabolic activity in 18F-fluorodeoxyglucose PET/CT, the same quantitative approach may be applied to quantifying sympathetic neuronal activity in 18F-FPBG PET/CT. Second, the shorter half-life of 18F (110 minutes), compared with that of 123I (13.2 hours), poses a reduced radiation risk to the patient, although the accurate dosimetry remains to be determined. This is particularly important in the case of neuroblastoma, a malignant tumor of infancy and childhood. Third, the short imaging time (2–3 hours) of 18F-FPBG PET/CT, in contrast to that of 123I-MIBG scintigraphy (4–24 hours), would substantially reduce inconvenience to the patient.
Sympathetic neuronal activity has been successfully evaluated by using 124I-labeled MIBG.11 124I-MIBG PET imaging has been mainly used for the purpose of pre-therapy dosimetry of 131I-MIBG treatment.12–14 A clinical trial of 124I-MIBG PET regarding neuroblastoma detection in comparison with 123I-MIBG scintigraphy is currently ongoing.15
To the best of our knowledge, our study was the first to use an 18F-labeled radiopharmaceutical for evaluating sympathetic neuronal activity in neuroblastoma. Despite the positive results obtained in the current case, further clinical studies with larger populations are warranted for confirming the efficacy of 18F-FPBG PET/CT and for obtaining approval from the appropriate regulatory government body. However, in light of the results obtained here, we suggest that 18F-FPBG is a promising PET imaging agent for evaluating sympathetic neuronal activity in neuroblastoma.
- Accepted September 10, 2014.
- Address correspondence to Won Woo Lee, MD, PhD (Professor), Department of Nuclear Medicine, Seoul National University Bundang Hospital, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea. E-mail:
Dr Suh drafted the initial manuscript and collected the data; Drs Park, Choi, BC Lee, and So designed the data collection instruments and coordinated and supervised data collection; Dr WW Lee had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of the data analysis, and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: Supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111627-1101-0000100).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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