Neurofibroma with increased uptake of [F-18]-fluoro-2 deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose interpreted as a metastatic lesion

We report a patient with a solitary spinal neurofibroma in the posterior mediastinum interpreted as a metastatic tumor. A 46-year-old female with rectal cancer who had undergone operation and subsequent adjuvant chemotherapy two years previously was referred to our department for a follow-up whole body FDG-PET study. PET scan revealed a mass with increased uptake of FDG (SUV=4.6) in the posterior mediastinum. MRI examination showed a dumbbell neurogenic tumor originating from the intercostal nerve at T6 level. A subsequent CT-guided biopsy demonstrated a neurofibroma.     

Intense uptake of [F-18]-fluoro-2 deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose in active pulmonary tuberculosis

FDG PET is well recognized for its utility in cancer workup. Nonetheless, the differentiation between malignant and benign pulmonary lesions by FDG PET is challenging. The authors report three proved cases of pulmonary tuberculosis in acute active and open stages. The activities and extents of infection were demonstrable in FDG PET, which could not be observed in either chest radiograph or computed tomography.     

High [<Superscript>18</Superscript>F] 2-fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose (FDG) uptake of adrenocortical adenoma showing subclinical Cushing's syndrome

A 48-year-old woman with left adrenal tumor, which showed increased uptake of [18F] 2-fluoro-2-deoxy-D-glucose (FDG) was presented. Her adrenal tumor was incidentally discovered, although she had no remarkable illness, and her blood pressure was normal. Hormonal examination including dexamethason suppression test and diurnal variation in serum cortisol level confirmed preclinical Cushing's syndrome. CT, MRI and 131I-adosterol scintigraphy showed findings consistent with adenoma. FDG-PET revealed that tumor had standardized uptake value of 4.8, which was higher than usual benign tumors. Histological diagnosis of the resected adrenal tumor was adrenocortical adenoma without evidence of malignancy. Although the current literature showed that adenomas in general did not exhibit increased FDG uptake, adenoma in the present case with subclinical Cushing's syndrome showed intense uptake of FDG, suggesting FDG-PET could evaluate hormonal function of an adrenocortical adenoma in a completely asymptomatic normocortisolism patient.     

Ovarian cancer recurrence: role of whole-body positron emission tomography using 2-[fluorine-18]-fluoro-2-deoxy-<Emphasis Type="SmallCaps">D</Emphasis>-glucose

This study was designed to assess the value of whole-body positron emission tomography (PET) using 2-[fluorine-18]-fluoro-2-deoxy- D-glucose (FDG) for the diagnosis of recurrent ovarian cancer. Twenty-five patients who had previously undergone surgery for ovarian cancer were imaged using whole-body FDG-PET. During the 4 weeks preceding the PET study, conventional imaging, comprising computed tomography (CT) and magnetic resonance (MR) imaging of the abdomen and/or pelvis, was performed and serum CA125 levels were measured. PET imaging was commenced at 60 min after the intravenous administration of FDG in all patients. PET results were compared with the results of conventional imaging and CA125 levels, and related to pathological findings and clinical follow-up for more than 6 months. FDG-PET showed a sensitivity of 80% (16/20), a specificity of 100% (5/5) and an accuracy of 84% accuracy (21/25) for the diagnosis of recurrent ovarian cancer. The sensitivity, specificity and accuracy of conventional imaging were 55% (11/20), 100% (5/5) and 64% (16/25), respectively. PET could detect recurrent lesions in seven of nine patients in whom conventional imaging was falsely normal, while conventional imaging was true positive in two of four patients with false-negative PET results. The CA125 results showed a sensitivity of 75% (15/20), a specificity of 100% (5/5) and an accuracy of 80% accuracy (20/25). Among the 15 patients with true-positive CA125 results, PET correctly detected abnormal foci of recurrence in 13 patients (86.7%) whereas conventional imaging showed recurrent lesions in only eight patients (53.3%). In conclusion, our preliminary study demonstrates that FDG-PET may be accurate and useful for the detection of tumour recurrence when conventional imaging is inconclusive or negative, especially in patients with abnormal CA125 levels.     

Differentiation between malignant and benign pathologic fractures with F-18-fluoro-2-deoxy-<Emphasis Type="SmallCaps">D</Emphasis>-glucose positron emission tomography/computed tomography

Objective To evaluate the efficacy of F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) in differentiating malignant from benign pathologic fractures. Materials and methods F-18 FDG PET/CT was performed on 34 patients with pathologic fractures between May 2004 and June 2007. Fractures were located in tubular bones (26), in the pelvis (six), in the spine (one) and in a rib (one). The FDG uptake pattern at the fracture site was described, whether FDG uptake occurred in the marrow or cortex and soft tissue. Maximum standardized uptake values (SUVmax, the largest value at the region of interest) were measured at the fracture site, including cortical bone, bone marrow and soft tissue. As a reference standard, biopsy was used for 12 patients and clinical follow-up for 22 patients. Sensitivity, specificity and diagnostic accuracy of PET/CT were calculated. Results There were 19 malignant and 15 benign fractures. In the malignant fractures, PET/CT demonstrated high (mean SUVmax 12.0, range 4.3 to 45.7) F-18 FDG uptake in bone marrow in most cases (17 of 19). In benign fractures, there was low FDG uptake (mean SUVmax 2.9, range 0.6 to 5.5) within cortical bone or adjacent soft tissue around the fracture, rarely in the marrow. There were significant differences in the pattern of intramedullary FDG uptake (P < 0.001) and in the mean SUVmax (P < 0.01) between malignant and benign fractures. The sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT were 89.5%, 86.7% and 88.2%, respectively, with a cut-off SUVmax set at 4.7. The time interval between fracture and PET/CT did not significantly influence FDG uptake at the fracture site. Conclusion F-18 FDG PET/CT reliably differentiated between malignant and benign fractures based on the SUVmax and based on medullary uptake, which was characteristic for malignant fractures. This research was supported by the Yeungnam University research grants in 2007.     

2-[Fluorine-18]-fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose positron emission tomography/computed tomography versus whole-body diffusion-weighted MRI for detection of malignant lesions: initial experience

Objectives The new magnetic resonance whole body diffusion-weighted imaging with background body signal suppression (DWIBS) uses short tau inversion recovery-echo planar imaging sequence under normal respiration. DWIBS is different from 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG PET) imaging in technology, but their images are similar. We compared the two modalities regarding the detection and characterization of malignant tumors. Methods DWIBS and ¹⁸F-FDG PET/computed tomography (CT) were performed on 16 cancer patients on the same day. The diagnoses were the following: lung cancer (n = 12), colon cancer (n = 2), breast cancer (n = 1), and pulmonary metastasis (n = 1). A total of 27 malignant tumors (15 lung cancer, 5 pulmonary metastases of parathyroid cancer, 3 pulmonary metastases of lung cancer, 3 colon cancer, 1 breast cancer) and seven reference organs around malignant lesions (two liver regions, four normal lymph nodes, one muscle region) were evaluated visually and quantitatively using the apparent diffusion coefficient (ADC) (×10⁻³ mm²/s) and standardized uptake value (SUV). Results Twenty-five (92.6%) of the 27 malignant lesions were detected visually with DWIBS imaging in contrast to 22 malignant tumors (81.5%) with ¹⁸F-FDG PET/CT imaging. The quantitative evaluation showed that there was a significant difference between the mean SUVs of the reference organs (n = 7, 1.48 ± 0.62) and the malignant (n = 22, 5.36 ± 2.80) lesions (P < 0.01). However, there was no significant difference between the mean ADCs of the reference organs (n = 7, 1.54 ± 0.24) and the malignant (n = 25, 1.18 ± 0.70) lesions. Conclusions DWIBS can be used for the detection of malignant tumors or benign tumors; however, it may be difficult to differentiate between benign and malignant lesions by ADC.     

Evaluation of whole-body cancer screening using <Superscript>18</Superscript>F-2-deoxy-2-fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose positron emission tomography: a preliminary report

OBJECTIVE: (18)F-2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) is a promising screening modality targeting whole body. However, the validity of PET cancer screening remains to be assessed. Even the screening accuracy for whole-body screening using FDG-PET has not been evaluated. In this study, we investigated the screening accuracy of PET cancer screening. METHODS: A total of 2911 asymptomatic participants (1629 men and 1282 women, mean age 59.79 years) underwent both FDG-PET and other thorough examinations for multiple organs (gastrofiberscopy, total colonofiberscopy or barium enema, low-dose thin section computed tomography and sputum cytology, abdominal ultrasonography, an assay of prostate-specific antigen, mammography, mammary ultrasonography, Pap smear for the uterine cervix, and magnetic resonance imaging for the endometrium and ovaries) between February 2004 and January 2005, and followed sufficiently. The detection rate, sensitivity, specificity, and positive predictive value of FDG-PET were calculated using cancer data obtained from all examinations along with a 1 year follow-up. RESULTS: From among 2911 participants FDG-PET found 28 cancers, 129 cancers were PET negative. PET-positive cancers comprised seven colorectal cancers, four lung cancers, four thyroid cancers, three breast cancers, two gastric cancers, two prostate cancers, two small intestinal sarcomas (gastrointestinal stromal tumors), one malignant lymphoma, one head and neck malignancy (nasopharyngeal carcinoid tumor), one thymoma, and one hepatocellular carcinoma. PET-negative cancers included 22 gastric cancers and 20 prostate cancers that were essentially difficult to detect using FDG-PET. The overall detection rate, sensitivity, specificity, and positive predictive value were estimated to be 0.96%, 17.83%, 95.15%, and 11.20%, respectively. CONCLUSIONS: FDG-PET can detect a variety of cancers at an early stage as part of a whole-body screening modality. The detection rate of PET cancer screening was higher than that of other screening modalities, which had already shown evidence of efficacy. However, the sensitivity of PET cancer screening was lower than that of other thorough examinations performed at our institute. FDG-PET has some limitations, and cancer screening using only FDG-PET is likely to miss some cancers.     

Potential impact of [<Superscript>18</Superscript>F]3'-deoxy-3'-fluorothymidine versus [<Superscript>18</Superscript>F]fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose in positron emission tomography for colorectal cancer

Ohne Zusammenfassung     

Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-<Emphasis Type="SmallCaps">d</Emphasis>-glucose with positron emission tomography in patients with small cell lung cancer

Objective  

The objective of this study is to determine whether 2-deoxy-2-[18F] fluoro-d-glucose with positron emission tomography (FDG-PET) imaging and quantitative PET parameters can predict outcome and differentiate patients with limited disease (LD) from extensive disease (ED) in patients with small cell lung cancer (SCLC).     

Predictive Value of Preoperative Volume-Based 18F-2-Fluoro-2-Deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-Glucose Positron Emission Tomography/Computed Tomography Parameters in Patients with Resectable Lung Adenocarcinoma

Purpose

This study aimed to investigate the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volume-based PET parameters, using ¹⁸F-2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with surgically resectable lung adenocarcinoma.

Methods

We retrospectively evaluated 149 patients with lung adenocarcinoma who underwent ¹⁸F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax), MTV, and TLG of the primary tumor with threshold value of SUVmax 30, 40, and 50% were calculated, respectively. To compare the predictive performance of volume-based PET parameters, recurrence-free survival was assessed using the Kaplan-Meier method.

Results

The study included 70 males and 79 females with an average age of 65.8 years. The median follow-up time was 45.4 months. Recurrence was observed in 53 patients (35.6%). The mean?±?SD SUVmax, MTV_30%, and TLG_30% of the entire cohort were 4.79?±?2.94, 19.45?±?24.85, and 56.43?±?101.88, respectively. The cut-off values of MTV_30% and TLG_30% for recurrence were 11.07 ad 30.56, respectively. The 1-year recurrence-free survival (RFS) rate was 96.5% in low-MTV_30% patients compared with 86.2% in high-MTV_30% patients (p?=?0.018) and 96.0% in low-TLG_30% patients compared with 88.5% in high-TLG_30% patients (p?<?0.001). On univariate and multivariate analysis, TLG_30% (HR, 2.828, p?<?0.001; HR, 2.738, p?<?0.001, respectively) was an independent prognostic factor for predicting recurrence-free survival (RFS).

Conclusion

TLG_30% value was observed to be a significant prognostic factor for RFS in patients with lung adenocarcinoma treated by surgical resection.

     

Clinical significance of 2-[<Superscript>18</Superscript>F]fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose positron emission tomography for the assessment of <Superscript>131</Superscript>I-metaiodobenzylguanidine therapy in malignant phaeochromocytoma

Purpose  

The aim of this study was to evaluate the significance of 2-[¹⁸F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in the assessment of the therapeutic response to ¹³¹I-metaiodobenzylguanidine (MIBG) in malignant phaeochromocytoma.     

Diagnosis of tumor in the nasal cavity and paranasal sinuses with [<Superscript>11</Superscript>C]choline PET: Comparative study with 2-[<Superscript>18</Superscript>F]fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose (FDG) PET

[11C]choline (11C-choline) positron emission tomography (PET) was performed to evaluate its clinical utility in the diagnosis of tumors in the nasal cavity and paranasal sinuses. We studied 22 patients with suspicion of malignant tumors in the nasal cavity and paranasal sinuses. Tumor uptake of 11C-choline was measured with standardized uptake value (SUV) and correlated with the pathological diagnosis. 2-[18F]fluoro-2-deoxy-D-glucose (FDG) PET was performed in all patients for comparison. Both 11C-choline and FDG PET depicted squamous cell carcinoma showing an increased activity significantly higher than that of normal tissue, and these SUVs were significantly higher than those of benign lesions. FDG uptake in malignant tumors as a whole was variable. Although 11C-choline uptake in squamous cell carcinoma was lower than FDG uptake, 11C-choline uptake in malignant tumors was relatively uniform and statistical significance was found. PET with 11C-choline may be useful to diagnosis tumors in the nasal cavity and paranasal sinuses.     

Value of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="SmallCaps">l</Emphasis>-tyrosine PET for the diagnosis of recurrent glioma

Purpose The prognosis of patients with recurrent gliomas depends on reliable and early diagnosis of tumour recurrence after initial therapy. In this context, magnetic resonance imaging (MRI) and computed tomography (CT) often fail to differentiate between radiation- and tumour-induced contrast enhancement. Furthermore, absence of contrast enhancement, or even of ¹⁸F-fluorodeoxyglucose uptake in PET, does not exclude recurrence. The aim of this study was to establish the diagnostic value of O-(2-[¹⁸F]fluoroethyl)-l-tyrosine (FET) PET in recurrent gliomas.Methods Fifty-three patients with glioma (primary grading: 27=WHO grade IV, 16=grade III, 9=grade II, 1=grade I) and clinically suspected recurrence underwent FET PET scans 4–180 months after different treatment modalities. For semiquantitative evaluation, maximal SUV (SUV_max) and mean SUV within 80% and 70% isocontour thresholds (SUV₈₀/SUV₇₀) were evaluated and the respective ratios to the background (BG) were calculated. PET results were correlated with MRI/CT, clinical follow-up or biopsy findings.Results All patients presented with FET uptake, of varying intensity, in the area of the primary tumour after initial therapy. In the 42 patients with confirmed recurrence, there was additional distinct focal FET uptake with significantly higher values compared with those in the 11 patients without clinical signs of recurrence and showing only low and homogeneous FET uptake at the margins of the resection cavity. With respect to tumour grading, there was a slight but non-significant increase from WHO II (SUV_max/BG: 2.53±0.28) to WHO III (SUV_max/BG: 2.84±0.49) and WHO IV (SUV_max/BG: 3.55±1.07) recurrence.Conclusion FET PET reliably distinguishes between post-therapeutic benign lesions and tumour recurrence after initial treatment of low- and high-grade gliomas.     

Associations between liver <Superscript>18</Superscript>F fluoro-2-deoxy-<Emphasis Type="SmallCaps">d</Emphasis>-glucose accumulation and various clinical parameters in a Japanese population: influence of the metabolic syndrome

Purpose  

Liver demonstrates a heterogeneous ¹⁸F fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake pattern and sometimes shows an abnormally increased uptake even when there is no malignant tissue. The aim of this study was to evaluate the relationships of liver ¹⁸F-FDG uptake as related to physical factors, fatty liver, blood glucose (BG), and other biochemical data.     

Comparison of subcutaneous and intraperitoneal injection of <Emphasis Type="SmallCaps">d</Emphasis>-luciferin for in vivo bioluminescence imaging

Purpose  We compared subcutaneous (SC) injection and intraperitoneal (IP) injection of d-luciferin for in vivo bioluminescence imaging (BLI) to determine the utility of SC injection. Methods  Mice bearing SC tumours stably expressing firefly luciferase underwent in vivo BLI using SC and IP injection of d-luciferin. BLI studies were repeated at an interval of 3 h using a given injection route to assess repeatability and using different injection routes to assess correlation. In mice bearing both SC and IP tumours, BLI was performed successively using intravenous (IV), SC, and IP injection of d-luciferin. Haematological malignancy model mice underwent BLI using SC and IP injection. Results  In SC tumours, the peak time was slightly shorter and the peak signal was greater using SC injection than using IP injection. The repeatability of determining peak signals was comparable between the two injection routes, and a good correlation was observed between them. In mice bearing both SC and IP tumours, signals from IP tumours relative to those from SC tumours were much greater using IP injection than using IV or SC injection. In the haematological malignancy model, signals from the spleen relative to those from the bone marrow were greater using IP injection than using SC injection. Conclusion  In addition to rare injection failure, the IP injection of d-luciferin led to the overestimation of signals from IP tissues. For BLI, SC injection was shown to be a convenient alternative to IP injection.     

The potential use of 2-[<Superscript>18</Superscript>F]fluoro-2-deoxy-<Emphasis Type="SmallCaps">D</Emphasis>-galactose as a PET/CT tracer for detection of hepatocellular carcinoma

Purpose  

The aim of the study was to evaluate the feasibility of using the hepatocyte-specific positron emission tomography (PET) tracer 2-[¹⁸F]fluoro-2-deoxy-D-galactose (FDGal) as a tracer for hepatocellular carcinoma (HCC).     

Liver uptake of free fatty acids in vivo in humans as determined with 14(<Emphasis Type="Italic">R</Emphasis>,<Emphasis Type="Italic">S</Emphasis>)-[<Superscript>18</Superscript>F]fluoro-6-thia-heptadecanoic acid and PET

Increased delivery of circulating free fatty acids (FFA) to the liver has been implicated in the pathogenesis and progression of diabetes. The liver is inaccessible for direct measurement in humans in vivo. We measured liver FFA uptake with positron emission tomography (PET) and 14(R,S)-[¹⁸F]fluoro-6-thia-heptadecanoic acid ([¹⁸F]FTHA) in healthy men. We evaluated the use of graphical analysis and linear fit to describe uptake data over time, and compared the use of metabolite-corrected vs uncorrected input functions. Rapid accumulation of tracer in the liver was observed with time, leading to progressively higher tissue to blood radioactivity ratios. Using metabolite-corrected input function curves, linear fit to the data (r value) exceeded 0.99 in all subjects, during each fitting time frame. Values of liver FFA influx rate constant and uptake were 0.34±0.01 ml min^–1 ml^–1 and 0.20±0.02 µmol min^–1 ml^–1, respectively, and were minimally affected by the choice of the fitting interval. Expressed per unit mass, liver FFA uptake was ~50 times higher than that reported in skeletal muscle; in the whole organ, FFA uptake was twice as high as in skeletal muscles. The use of metabolite-uncorrected input functions significantly worsened the spread of data around the fitted line and led to a remarkable underestimation of liver FFA uptake at all time intervals. In conclusion, our data provide non-invasive quantification of hepatic FFA uptake in humans, showing the liver to handle a high FFA flux. [¹⁸F]FTHA-PET appears a valuable tool for the investigation of hepatic FFA turnover in humans.     

Uptake of 4-borono-2-[<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">L</Emphasis>-phenylalanine in sporadic and neurofibromatosis 2-related schwannoma and meningioma studied with PET

Purpose Meningiomas and schwannomas associated with neurofibromatosis 2 (NF2) are difficult to control by microsurgery and stereotactic radiotherapy alone. Boron neutron capture therapy (BNCT) is a chemically targeted form of radiotherapy requiring increased concentration of boron-10 in tumour tissue. PET with the boron carrier 4-borono-2-[¹⁸F]fluoro-L-phenylalanine ([¹⁸F]FBPA) allows investigation of whether 4-borono-L-phenylalanine (BPA) concentrates in NF2 tumours, which would make BNCT feasible. Methods We studied dynamic uptake of [¹⁸F]FBPA in intracranial meningiomas (n=4) and schwannomas (n=6) of five sporadic and five NF2 patients. Tracer input function and cerebral blood volume were measured. [¹⁸F]FBPA uptake in tumour and brain was assessed with a three-compartmental model and graphical analysis. These, together with standardised uptake values (SUVs), were used to define tumour-to-brain [¹⁸F]FBPA tissue activity gradients. Results Model fits with three parameters K ₁ (transport), k ₂ (reverse transport) and k ₃ (intracellular metabolism) were found to best illustrate [¹⁸F]FBPA uptake kinetics. Maximum SUV was two- to fourfold higher in tumour as compared with normal brain and independent of NF2 status. The increased uptake was due to higher transport of [¹⁸F]FBPA in tumour. In multiple-time graphical analysis (MTGA, Gjedde-Patlak plot) the tumour-to-brain [¹⁸F]FBPA influx constant (K _i -MTGA) ratios varied between 1.8 and 5.4 in NF2-associated tumours while in sporadic tumours the ratio was 1–1.4. Conclusion [¹⁸F]FBPA PET offers a viable means to evaluate BPA uptake in meningiomas and schwannomas in NF2. Based on our results on tumour uptake of [¹⁸F]FBPA, some of these benign neoplasms may be amenable to BNCT. Financial support: This work was sponsored in part by the Department of Army, Grant No. DAMD17-00-1-0545. The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, MD 21702-5014, USA, is the awarding and administering acquisition office. The content of the information of this paper does not necessarily reflect the position or the policy of the US Government.     

Reliable radiosynthesis of 4-[<Superscript>10</Superscript>B]borono-2-[<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">l</Emphasis>-phenylalanine with quality assurance for boron neutron capture therapy-oriented diagnosis

Objective

The aim of this study was to establish a reliable and routine method for the preparation of 4-[¹⁰B]borono-2-[¹⁸F]fluoro-l-phenylalanine (l-[¹⁸F]FBPA) for boron neutron capture therapy-oriented diagnosis using positron emission tomography.

Methods

To produce l-[¹⁸F]FBPA by electrophilic fluorination of 4-[¹⁰B]borono-l-phenylalanine (l-BPA) with [¹⁸F]acetylhypofluorite ([¹⁸F]AcOF) via [¹⁸F]F₂ derived from the ²⁰Ne(d,α)¹⁸F nuclear reaction, several preparation parameters and characteristics of l-[¹⁸F]FBPA were investigated, including: pre-irradiation for [¹⁸F]F₂ production, the carrier F₂ content in the Ne target, l-BPA-to-F₂ ratios, separation with high-performance liquid chromatography (HPLC) using 10 different eluents, enantiomeric purity, and residual trifluoroacetic acid used as the reaction solvent by gas chromatography-mass spectrometry.

Results

The activity yields and molar activities of l-[¹⁸F]FBPA (n?=?38) were 1200?±?160 MBq and 46–113 GBq/mmol, respectively, after deuteron-irradiation for 2 h. Two 5 min pre-irradiations prior to [¹⁸F]F₂ production for ¹⁸F-labeling were preferable. For l-[¹⁸F]FBPA synthesis, 0.15–0.2% of carrier F₂ in Ne and l-BPA-to-F₂ ratios?>?2 were preferable. HPLC separations with five of the 10 eluents provided injectable l-[¹⁸F]FBPA without any further formulation processing, which resulted in a synthesis time of 32 min. Among the five eluents, 1 mM phosphate-buffered saline was the eluent of choice. The l-[¹⁸F]FBPA injection was sterile and pyrogen-free, and contained very small amounts of D-enantiomer (<?0.1% of l-[¹⁸F]FBPA), l-BPA (<?1% of l-FBPA), and trifluoroacetic acid (<?0.5 ppm).

Conclusions

l-[¹⁸F]FBPA injection was reliably prepared by the electrophilic fluorination of l-BPA with [¹⁸F]AcOF followed by HPLC separation with 1 mM phosphate-buffered saline.

     

The added value of [<Superscript>18</Superscript>F]fluoro-<Emphasis Type="SmallCaps">L</Emphasis>-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children

Purpose Neuroendocrine diseases are a heterogeneous group of entities with the ability to take up amine precursors, such as L-DOPA, and convert them into biogenic amines, such as dopamine. Congenital hyperinsulinism of infancy (HI) is a neuroendocrine disease secondary to either focal adenomatous hyperplasia or a diffuse abnormal pancreatic insulin secretion. While focal hyperinsulinism may be reversed by selective surgical resection, diffuse forms require near-total pancreatectomy when resistant to medical treatment. Here, we report the diagnostic value of PET with [¹⁸F]fluoro-L-DOPA in distinguishing focal from diffuse HI. Methods Forty-nine children were studied with [¹⁸F]fluoro-L-DOPA. A thoraco-abdominal scan was acquired 45–65 min after the injection of 4.2 ± 1.0 MBq/kg of [¹⁸F]fluoro-L-DOPA. Additionally, 12 of the 49 children were submitted to pancreatic venous catheterisation for blood samples (PVS) and 31 were also investigated using MRI. Results We identified abnormal focal pancreatic uptake of [¹⁸F]fluoro-L-DOPA in 15 children, whereas diffuse radiotracer uptake was observed in the pancreatic area in the other 34 patients. In children studied with both PET and PVS, the results were concordant in 11/12 cases. All patients with focal radiotracer uptake and nine of the patients with diffuse pancreatic radiotracer accumulation, unresponsive to medical treatment, were submitted to surgery. In 21 of these 24 patients, the histopathological results confirmed the PET findings. In focal forms, selective surgery was followed by clinical remission without carbohydrate intolerance. Conclusion These data demonstrate that PET with [¹⁸F]fluoro-L-DOPA is an accurate non-invasive technique allowing differential diagnosis between focal and diffuse forms of HI.