18F-FDG Accumulation Research Articles

Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway.

It has been reported that irisin regulated exercise-mediated adipocyte browning; however, the systematical effects of irisin on the metabolism of glucose and lipid in diabetes are largely unknown. In the present study, we investigated the role and underlying mechanism of irisin in glucose utilization and lipid metabolism in diabetic mice. A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated. Irisin improved glucose tolerance and glucose uptake as evidenced by increased (18)F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-β phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid β-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes. Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.

Increased bone marrow uptake of 18F-FDG in leukemia patients: preliminary findings

The aim of this retrospective study was to evaluate the characteristics of increased bone marrow uptake of 18F-FDG in patients with leukemia who underwent whole-body 18F-FDG PET/CT. The 18F-FDG PET/CT images of 9 patients with histologically proven leukemia were reviewed. The accumulation of 18F-FDG in the bone marrow was evaluated, and was compared with histological subtype, clinical course, and hematological findings. Nine patients (4 males, 5 females; age range, 5–58 years) had increased bone marrow uptake of 18F-FDG, including 6 patients with acute lymphoblastic leukemia, 1 with acute myeloid leukemia, 1 with chronic myeloid leukemia, and 1 with mature B cell neoplasm. Bone marrow uptake was generally diffuse but focal or inhomogeneous uptake was common, especially in the upper and lower extremities. Patients with increased bone marrow uptake of 18F-FDG commonly complained of fever and bone pain. No correlations between 18F-FDG uptake and peripheral blood findings were observed. Patients with leukemia may have increased bone marrow uptake of 18F-FDG on PET/CT, possibly reflecting leukemic cell activity. Leukemia can be included in the differential diagnosis when increased bone marrow uptake of 18F-FDG is observed.

Spatiotemporal PET Imaging of Dynamic Metabolic Changes After Therapeutic Approaches of Induced Pluripotent Stem Cells, Neuronal Stem Cells, and a Chinese Patent Medicine in Stroke.

This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia-reperfusion injury. Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P < 0.05) or glucose transporter-1 expression (P < 0.01). Immunohistochemical and immunofluorescence studies found that transplanted iPSCs survived and migrated to the ischemic region and expressed protein markers for cells of interest. Spatiotemporal PET imaging with (18)F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia-reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually.

Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and sialadenitis (Mikulicz's disease) and for differentiating it from Sjögren's syndrome (SS), with an emphasis on sonography.

IntroductionThe aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in the imaging features between IgG4-DS and Sjögren’s syndrome (SS).MethodsThirty-nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were enrolled. Images of the parotid and submandibular glands obtained using sonography, 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and maxillofacial radiologists randomly reviewed the arranged image sets under blinded conditions. Each observer scored the confidence rating regarding the presence of the characteristic imaging findings using a 5-grade rating system. After scoring various findings, diagnosis was made as normal, IgG4-DS or SS, considering all findings for each case.ResultsOn sonography, multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and obscuration of submandibular gland configuration were detected mainly in patients with SS (median scores 4, 4 and 3, respectively). Reticular and nodal patterns were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT revealed a tendency for abnormal 18F-FDG accumulation and swelling of both the parotid and submandibular glands in patients with IgG4-DS, particularly in the submandibular glands. On MRI, SS had a high score regarding the findings of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5). Sonography showed the highest values among the four imaging modalities for sensitivity, specificity and accuracy. There were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058) concerning accuracy.ConclusionsChanges in the submandibular glands affected by IgG4-DS could be easily detected using sonography (characteristic bilateral nodal/reticular change) and FDG-PET/CT (abnormal 18F-FDG accumulation). Even inexperienced observers could detect these findings. In addition, sonography could also differentiate SS. Consequently, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, involves no radiation exposure and is an effective imaging modality.

Relationship Between 18F-FDG PET/CT Scans and KRAS Mutations in Metastatic Colorectal Cancer.

Several studies have shown that KRAS mutations in colorectal cancer (CRC) result in the lack of response to anti-epidermal growth factor receptor-based therapy; thus, KRAS mutational testing has been incorporated into routine clinical practice. However, 1 limitation of this test is the heterogeneity of KRAS status, which can be either intratumoral heterogeneity within an individual primary CRC or discordant KRAS status between a primary CRC and its corresponding metastases. We previously reported that (18)F-FDG accumulation was significantly higher in primary CRCs with mutated KRAS than in those with wild-type KRAS. However, the clinical utility of the previous report has been limited because endoscopic biopsy for testing KRAS status is safe and feasible only in primary CRC. The purpose of this study was to investigate whether KRAS status is associated with (18)F-FDG accumulation in metastatic CRC and whether (18)F-FDG PET/CT scans can be used to predict the KRAS status of metastatic CRC. A retrospective analysis was performed on 55 metastatic CRC tumors that were identified by (18)F-FDG PET/CT before surgical resection. Maximum standardized uptake value (SUVmax) of the respective metastatic tumor was calculated from (18)F-FDG accumulation. From the analysis with the 55 tumors, no significant correlation was found between SUVmax and KRAS status. We next analyzed only tumors larger than 10 mm to minimize the bias of partial-volume effect and found that SUVmax was significantly higher in the KRAS-mutated group than in the wild-type group (8.3 ± 4.1 vs. 5.7 ± 2.4, respectively; P = 0.03). Multivariate analysis indicated that SUVmax remained significantly associated with KRAS mutations (P = 0.04). KRAS status could be predicted with an accuracy of 71.4% when an SUVmax cutoff value of 6.0 was used. (18)F-FDG accumulation into metastatic CRC was associated with KRAS status. (18)F-FDG PET/CT scans may be useful for predicting the KRAS status of metastatic CRC and help in determining the therapeutic strategies against metastatic CRC.

The effect of P-glycoprotein on 18F-FDG uptake in tumor-bearing nude mice

Objective To evaluate the relationship between 18F-FDG uptake and P-gp expression in Bcap37 or Bcap37/MDR1 tumor-bearing BALB/c nude mice. Methods Bcap37 or Bcap37/MDR1 cells were injected into BALB/c nude mice (1×107 cells/ml, 0.2 ml/mouse) to construct mice models. Bcap37(n=5) or Bcap37/MDR1 (n=5) tumor-bearing mice fasted for 6 h before imaging. After anesthesia, the mice were injected with 7.4 MBq of 18F-FDG via tail vein. The dynamic microPET scans were carried out for 90 min. On the microPET images, the ROI was drawn and the TAC was obtained. The next day, those 10 mice underwent dynamic microPET scans after injected with elacridar (GF120918) and 18F-FDG. Another 10 mice, 5 with Bcap37 tumors and 5 with Bcap37/MDR1 tumors, were used. After 7.4 MBq 18F-FDG with or without 2.0 mg/kg GF120918 was administered via tail vein, microPET images were acquired at 60 min. ROI was drawn over the tumors and SUVmean was obtained. Two-sample t test was used to analyze the data. Results GF120918 did not significantly alter the 18F-FDG accumulation curve in Bcap37 tumors, but significantly enhanced the 18F-FDG accumulation in Bcap37/MDR1 tumors. GF120918 did not influence 18F-FDG uptake (SUVmean) in Bcap37 tumors (1.052±0.028, 1.028±0.045, t=1.792, P>0.05), but significantly increased the SUVmean in Bcap37/MDR1 tumors (1.015±0.043, 0.712±0.031, t=3.365, P 0.05). Conclusions 18F-FDG is a substrate of P-gp. 18F-FDG imaging combined with GF120918 injection may be an effective noninvasive method for the detection of tumor's MDR. Key words: Breast neoplasms; Fluorine radioisotopes; Deoxyglucose; P-glycoprotein; Mice, nude

Oncocytic adenomas of thyroid-mimicking benign or metastatic disease on 18F-FDG-PET scan.

The literature is sparse concerning 18F-fluorodeoxyglucose (18F-FDG) accumulation in the Hürthle cell neoplasm (HCN) of the thyroid. Given the difficulty of accurately diagnosing HCN, even with ultrasound (US) and fine needle aspiration biopsy (FNAB), the ability to accurately characterize these lesions by 18F-FDG positron emission tomography (PET) would be of value. To describe six cases of oncocytic proliferation in the thyroid gland that mimics the presence of metastatic disease and was detected incidentally by an 18F-FDG PET scan. We conducted whole-body 18F-FDG PET examinations for cancer staging in 1862 oncological patients from 2012 to 2013. Among them, six subjects (4 women, 2 men; age range, 45-85 years) with focal-enhanced 18F-FDG accumulation in the thyroid gland were selected from the study population. This study group was further investigated using 99 m-Tc-pertechnetate scintigraphy, US, and FNAB. Two experienced nuclear physicians reviewed the images. Gray-scale US and color Doppler (CD) sonographic examinations of the thyroid were undertaken for all subjects using a sonographic device Logiq 5 Expert (GE Medical Systems, Osaka, Japan) equipped with a 7-12 MHz linear array transducer. In all six cases, abnormal 18F-FDG uptake was found locally in the thyroid. The average SUVmax of the HCN was 5.8 (range, 2.6-16). In all six cases, 99 m-Tc-pertechnetate scintigraphy showed a cold spot. Compared with normal parenchymal vascularity, five of the six masses were shown to be hypervascular by CD ultrasonography. On PET scans, oncocytic proliferations of the thyroid may mimic metastases of other malignancies. The focal-enhanced uptake of 18F-FDG PET may be associated with a focal increase in the metabolic activity of the thyroid parenchyma due to the presence of oncocytes. Our study emphasizes the importance of obtaining cytological evidence before making a diagnosis of metastatic disease.

Abstract P5-01-15: The uptake of 18F-fluorodeoxyglucose (18F-FDG) by normal breast tissues as measured by a dedicated breast positron emission tomography (PET) scanner: A preliminary study

Abstract Introduction Breast positron emission tomography (PET ) is a molecular imaging method which identifies breast cancers with high sensitivity and specificity. Dedicated breast PET scanners have an improved spatial resolution compared to whole body PET scanners, and are able to differentiate between glandular and fat tissues within the breast. The aim of this study is to determine how normal breast tissues take up 18F-FDG with time. Method In this IRB-approved prospective study, patients with a newly diagnosed invasive breast cancer who desired breast conservation surgery were recruited. Participants underwent bilateral breast PET scans using a two-ring dedicated breast PET scanner (MAMMI breast PET, Oncovision, GEM Imaging S.A.) after receiving a standard 18F-FDG dose of 5 mCu. After an uptake phase of 60 minutes, all patients were scanned at 3 time points: at 60 minutes, 90 minutes and 120 minutes post-injection. Reconstructed images obtained on the MAMMI breast PET scanner were then read and processed using the OsiriX software. For each scan performed at each time point, a series of continuous axial images through the central portion of the breast containing the nipple as a landmark was identified. Two elliptical 1cm2 regions of interest (ROI) were drawn, one on the central portion of the glandular parenchyma and a second on the fat. This was propagated through the included slices, after ensuring that the ROI lay entirely within the desired component of the breast in the same region for each breast. In the ipsilateral breast, the quadrant opposite the index tumor was used to avoid contamination. The mean SUV values for breast parenchyma and breast fat were measured, compared to the mammographic density of the breast tissues and tabulated against time. Results 9 patients participated in the study, yielding a total of 54 breast PET scans for analysis (bilateral scans for each patient at 3 time points). The mean SUV measurements for breast parenchyma ranged from 0.7 to 2.8 and the mean SUV measurements for breast fat ranged from 0.1 to 0.8. The mean SUV of breast parenchyma was approximately 3 to 4 times that of the mean SUV of breast fat at each time point. There was a gradual increase in the mean SUV of breast parenchyma and breast fat with time, although the increase appeared more pronounced with breast parenchyma. Patients with dense breast tissues tended to have a higher parenchymal mean SUV value. Conclusion Normal breast parenchyma demonstrates a greater uptake of 18F-FDG compared to breast fat tissues at a ratio of approximately 3-4 to 1. There is accumulation of 18F-FDG with time in both parenchymal and fatty tissues within the breast, more so with the former. Knowledge of the background SUV measurement of parenchymal tissues is important as this affects the SUV measurement of the underlying breast cancer. Increasing accumulation of FDG with time may decrease the contrast resolution of a cancer, especially in patients with dense breast parenchyma. Citation Format: Sze Yiun Teo, Jasper Chaal, Jung Ah Lee, Michel Herranz. The uptake of 18F-fluorodeoxyglucose (18F-FDG) by normal breast tissues as measured by a dedicated breast positron emission tomography (PET) scanner: A preliminary study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-01-15.

Urinary 8-hydroxy-2′-deoxyguanosine as a novel biomarker of inflammatory activity in patients with cardiac sarcoidosis

BackgroundInflammation and oxidative stress play a crucial role in the pathogenesis of cardiac sarcoidosis (SAR). We investigated whether urinary (U) 8-hydroxy-2′-deoxyguanosine (8-OHdG)—an oxidative DNA damage marker—was related to SAR inflammatory activity. MethodsU-8-OHdG levels were measured in 31 SAR patients, classified as active (n=17) or non-active (n=14) based on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG-PET/CT), 28 dilated cardiomyopathy (DCM) patients, and 30 controls. In active SAR patients, U-8-OHdG levels were reexamined and compared with 18F-FDG-PET/CT results at 6months after corticosteroid treatment to assess therapeutic response. ResultsImmunohistochemical examination of left ventricle (LV) autopsy samples from SAR patients revealed positive 8-OHdG staining in cardiomyocyte nuclei from LV sections showing 18F-FDG accumulation on PET/CT, while serum 8-OHdG levels were significantly higher in the coronary sinus than in the aortic root only in active SAR patients. U-8-OHdG levels in SAR patients were higher than those in controls, and significantly higher in active SAR patients than in non-active SAR and DCM patients. U-8-OHdG was a powerful predictor of active SAR in receiver operating characteristic curve analysis (AUC, 0.98; 95% CI, 0.94–1.02; optimal cutoff value, 13.1ng/mg creatinine), with a sensitivity of 88.2% and a specificity of 92.9%. U-8-OHdG levels in responders significantly decreased at 6months after corticosteroid treatment initiation, in proportion with the decrease in the focal cardiac uptake of 18F-FDG. ConclusionsU-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients.

18F-FDG PET/CT in patients with adult-onset Still's disease.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has become useful for the detection and diagnosis of inflammatory conditions, including rheumatic diseases, immunoglobulin (Ig) G4-related disease and giant cell arteritis. However, few articles based on small sample sizes (n = 7) diagnosed as adult-onset Still's disease (AOSD) have been published. The study aim was to observe the reliable characteristics and usefulness of (18)F-FDG PET/CT for the evaluation of consecutive patients with AOSD. Eligible patients were selected from among those who had undergone (18)F-FDG PET/CT between May 2007 and June 2014. Twenty-six consecutive AOSD patients were recruited retrospectively according to criteria set by Yamaguchi et al. All patients underwent evaluation by (18)F-FDG PET/CT. The characteristics and usefulness of (18)F-FDG PET/CT for evaluation of consecutive patients with AOSD were evaluated. All 26 patients had (18)F-FDG-avid lesion(s) related to their particular disease. Diffuse and homogeneous accumulation of (18)F-FDG was seen in the bone marrow (26/26; 100 %; maximum standardized uptake (SUVmax), 2.10-6.73) and spleen (25/26; 96.15 %). The SUVmax of affected lymph nodes was 1.3-9.53 (mean ± SD, 4.12 ± 2.24). The SUVmax and size factors (maximum diameter and areas) of affected lymph nodes were significantly different (P = 0.033 and P = 0.012, respectively). (18)F-FDG PET/CT showed the general distribution of (18)F-FDG accumulation. This factor helped to exclude malignant disease and aided the diagnosis of AOSD (42.3 %) in 11 cases when combined with clinical features and aided decisions regarding appropriate biopsy sites, such as the lymph nodes (n = 9) and bone marrow (n = 13). (18)F-FDG PET/CT is a unique imaging method for the assessment of metabolic activity throughout the body in subjects with AOSD. Characteristics or patterns of AOSD observed on (18)F-FDG PET/CT can be used for the indication and diagnosis or to guide the clinical management of ASOD.

Psoriatic Inflammation Facilitates the Onset of Arthritis in a Mouse Model

Psoriatic arthritis (PsA) is a seronegative, inflammatory joint disease associated with psoriasis. In most patients with PsA, skin lesions precede arthritis; however, the causality of skin inflammation for the development of arthritis remains unclear. Gp130F759/F759 knock-in (F759) mice develop autoimmune arthritis after 1 year of age through persistent signal transducer and activator of transcription 3 (Stat3) activation due to impairment in SOCS3-dependent negative regulation. Here, we crossed F759 mice with K5.Stat3C transgenic mice, in which keratinocytes express constitutive active Stat3 (Stat3C), leading to generation of psoriasis-like skin change. F759 mice harboring the K5.Stat3C transgene not only had aggravated skin lesions but also spontaneously developed arthritis with high penetrance in adjacent paws as early as 3 weeks of age. The joint lesions included swelling of the peripheral paws and nail deformities contiguous with the skin lesions, closely resembling PsA. Histopathologic study revealed enthesitis and bone erosions, with mononuclear cell infiltrates. Quantitative reverse transcriptase-PCR (RT-PCR), immunohistochemical analyses, and flow cytometry showed upregulation of the IL-23/T helper type 17 (Th17) pathway in affected joints. Furthermore, enforced generation of psoriasis-like skin inflammation by topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) in F759 mice induced swelling of the underlying joints. This animal model renders psoriatic inflammation as the driver of arthritis and helps to further understand the pathogenesis of PsA.

Pulmonary arteriovenous malformation mimicking a pulmonary tumour on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography.

Pulmonary arteriovenous malformations are rare congenital abnormal connections between the pulmonary arteries and veins. The patients are usually asymptomatic [1]. Although their aetiology is unclear, it is presumed that genetic abnormalities constitute a predisposition [1, 2]. An arteriovenous malformation might cause serious complications if it remains undiagnosed and untreated [3]. We report a unique case of focal 18F-fluorodeoxyglucose (18F-FDG) uptake in a pulmonary arteriovenous malformation mimicking a mass lesion. A 74-year-old female patient with cyanosis and clubbing in her fingers and toes was referred to the Nuclear Medicine Department for positron-emission tomography (PET)/computed tomography (CT) imaging to assess a solitary pulmonary nodule with irregular margins in the right upper lobe detected on CT (Figure 1A). The CT appearance suggested a malignant lesion. On 18F-FDG PET/CT, there was increased focal uptake in the pulmonary nodule, suggesting a mass lesion, possibly malignant (Figure 1B). There is no described typical uptake pattern for arteriovenous malformations in FDG PET/CT images. 18F-FDG accumulation in a pulmonary mass suggests malignancy in most cases, although FDG accumulates in several benign conditions. Pulmonary angiography revealed afferent and efferent vessels with high contrast accumulation. Based on these findings, a pulmonary arteriovenous malformation was diagnosed. Subsequently, the patient underwent right video-assisted thoracoscopic surgery, a mini-thoracotomy, and wedge resection. The specimen confirmed the diagnosis of pulmonary arteriovenous malformation (Figure 2). Figure 1 A – CT image showing a solitary pulmonary nodule in the anterior segment of the upper pole of the right lung. B – On 18F-FDG PET/CT, increased focal uptake was seen in the pulmonary nodule, suggesting a malignancy (SUVmax 4.2 kBq/ml) Figure 2 The specimen was stained with (A) haematoxylin and eosin and (B) Elastica van Gieson, which showed large and small vessels, confirming the diagnosis of pulmonary arteriovenous malformation Pulmonary arteriovenous malformations are often diagnosed radiologically [4–6]. A chest X-ray might reveal a solitary nodule or be completely normal. Thorax CT is usually the second diagnostic tool in a patient with a suspected pulmonary arteriovenous malformation [7, 8], which causes dyspnoea and cyanosis in most cases [1, 3]. Pulmonary angiography gives the ultimate diagnostic information [4, 8]. The CT appearance of our patient's arteriovenous malformation suggested a malignant solitary mass. The moderately increased FDG uptake also caused diagnostic confusion. There is no typical uptake pattern of arteriovenous malformations in FDG PET/CT images.

Chondromyxoid Fibroma of the Femur Can Not Be Differentiated ofrm Chondrosarcoma by 18F-FDG PET/CT, and Histopathology is Still the Final Diagnsotic Tool

Chondromyxoid fibroma is an extremely rare, benign cartilaginous tumor, which might be misdiagnosed as hondrosarcoma. Recent studies reported that PET/CT could distinguish benign cartilaginous tumors from chondrosarcomas with maximum Standardized Uptake Value (SUVmax) of more than 2.0. In the literature, 4 cases of chondromyxoid fibroma have been reported on PET/CT with high accumulation of 18FFDG. However, no paper has explained the reason for this high accumulation. In this paper, we present a case of femoral chondromyxoid fibroma and discuss the rational reason for high accumulation of 18F-FDG by PET/CT in accordance with histology. Here, a 20-year-old female presented with a lesion located in the medial aspect of the left distal femur. Radiography revealed an eccentric radiolucency in the metaphysis of the left distal femur. CT images clearly demonstrated a cortical destruction of the posterior wall. PET/CT images clearly demonstrated an abnormal 18F-FDG uptake of the distal aspect of the left femur with SUVmax value of 6.6, indicating a chondrosarcoma. In the present case, histology showed a number of multinucleated giant cells at the periphery of the lobules in the tumor, which can explain the high accumulation.

Primary pulmonary amyloidosis misdiagnosed as malignancy on dual-time-point fluoro-deoxyglucose positron emission tomography/computed tomography: A case report and review of the literature

Primary pulmonary amyloidosis is an uncommon manifestation, characterized by amyloid deposition in the lungs and other associated tissue. The clinical presentation of amyloidosis is variable, with non-specific symptoms. The current study reports the case of a 59-year-old female presenting with primary pulmonary amyloidosis, indistinguishable from lung malignancy based on 18F-fluoro-deoxyglucose (18F-FDG) accumulation on dual-time-point (DTP) FDG-positron emission tomography/computed tomography (PET/CT) imaging and the similarities in morphological changes. A percutaneous CT-guided thoracoscopic biopsy was subsequently performed. Histological examination revealed that the specimens contained amorphous, homogeneous material with a number of polyclonal plasma cells, lymphocytes and giant cells. A diagnosis of primary nodular parenchymal pulmonary amyloidosis was determined, and the patient was discharged without chemotherapy. The patient remained in good clinical condition during follow-up. The present case indicated that localized nodular amyloidosis with increased FDG uptake on DTP FDG PET must be considered in the differential diagnosis of growing lung nodules, and that a histological examination must be conducted to distinguish this condition from malignancies of the lung.

Clinically relevant strategies for lowering cardiomyocyte glucose uptake for 18F-FDG imaging of myocardial inflammation in mice.

Myocardial inflammation is an emerging target for novel therapies and thus for molecular imaging. Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has been employed, but requires an approach for suppression of cardiomyocyte uptake. We tested clinically viable strategies for their suitability in mouse models in order to optimize preclinical imaging protocols. C57BL/6 mice (n = 56) underwent FDG PET under various conditions. In healthy animals, the effect of low-dose (5units/kg) or high-dose (500units/kg, 15min prior) intravenous heparin, extended fasting (18h) and the impact of conscious injection with limited, late application of isoflurane anaesthesia after 40min of conscious uptake were examined in comparison to ketamine/xylazine anaesthesia. Conscious injection/uptake strategies were further evaluated at 3days after permanent coronary artery occlusion. Under continuous isoflurane anaesthesia, neither heparin administration nor extended fasting significantly impacted myocardial (18)F-FDG accumulation. Injection with 40min uptake in awake mice resulted in a marked reduction of global myocardial (18)F-FDG uptake compared to standard isoflurane anaesthesia (5.7 ± 1.1%ID/g vs 30.2 ± 7.9%ID/g, p < 0.01). Addition of heparin and fasting further reduced uptake compared to conscious injection alone (3.8 ± 1.5%ID/g, p < 0.01) similar to ketamine/xylazine (2.4 ± 2.2%ID/g, p < 0.001). In the inflammatory phase, 3days after myocardial infarction, conscious injection/uptake with and without heparin/fasting identified a marked increase in myocardial (18)F-FDG accumulation that was similar to that observed under ketamine/xylazine. Continuous isoflurane anaesthesia obscures any suppressive effect of heparin or fasting on cardiomyocyte glucose utilization. Conscious injection of FDG in rodents significantly reduces cardiomyocyte uptake and enables further suppression by heparin and fasting, similar to clinical observations. In contrast to ketamine/xylazine, this represents a more physiological, translatable strategy for suppression of cardiomyocyte (18)F-FDG uptake when targeting myocardial inflammation.

Regulation of 18F-FDG accumulation in colorectal cancer cells with mutated KRAS.

KRAS gene mutations occur in approximately 40% of colorectal cancers (CRCs) and are associated with resistance to anti-epidermal growth factor receptor antibody therapy. We previously demonstrated that (18)F-FDG accumulation in PET was significantly higher in CRCs with mutated KRAS than in those with wild-type KRAS in a clinical setting. Here, we investigated the mechanisms by which mutated KRAS increased (18)F-FDG accumulation. Using paired isogenic human CRC cell lines that differ only in the mutational status of the KRAS gene, we measured (18)F-FDG accumulation in these cells in vitro and in vivo. We also investigated the roles of proteins that have a function in (18)F-FDG accumulation. Finally, we examined the relationship among mutated KRAS, hypoxia-inducible factor 1α (HIF-1α), and maximum standardized uptake value with 51 clinical CRC samples. In the in vitro experiments, (18)F-FDG accumulation was significantly higher in KRAS-mutant cells than in wild-type controls under normoxic conditions. The expression levels of glucose transporter 1 (GLUT1) and hexokinase type 2 (HK2) were higher in KRAS-mutant cells, and (18)F-FDG accumulation was decreased by knockdown of GLUT1. Hypoxic induction of HIF-1α was higher in KRAS-mutant cells than in wild-type controls; in turn, elevated HIF-1α resulted in higher GLUT1 expression and (18)F-FDG accumulation. In addition, HIF-1α knockdown decreased (18)F-FDG accumulation under hypoxic conditions only in the KRAS-mutant cells. Small-animal PET scans showed in vivo (18)F-FDG accumulation to be significantly higher in xenografts with mutated KRAS than in those with wild-type KRAS. The immunohistochemistry of these xenograft tumors showed that staining of GLUT1 was consistent with that of HIF-1α and pimonidazole. In a retrospective analysis of clinical samples, KRAS mutation exhibited a significantly positive correlation with expressions of GLUT1 and HIF-1α and with maximum standardized uptake value. Mutated KRAS caused higher (18)F-FDG accumulation possibly by upregulation of GLUT1; moreover, HIF-1α additively increased (18)F-FDG accumulation in hypoxic lesions. (18)F-FDG PET might be useful for predicting the KRAS status noninvasively.

Correlation of 18F-BPA and 18F-FDG uptake in head and neck cancers

Background and purposeThe aim of this study was to compare the accumulation of 4-borono-2-18F-fluoro-phenylalanine (18F-BPA) with that of 18F-fluorodeoxyglucose (18F-FDG) in head and neck cancers, and to assess the usefulness of 18F-FDG PET for screening candidates for boron neutron capture therapy (BNCT). Material and methodsTwenty patients with pathologically proven malignant tumors of the head and neck were recruited from March 2012 to January 2014. All patients underwent both whole-body 18F-BPA PET/CT and 18F-FDG PET/CT within 2weeks of each other. The uptakes of 18F-BPA and 18F-FDG at 1h after injection were evaluated using the maximum standardized uptake value (SUVmax). ResultsThe accumulation of 18F-FDG was significantly correlated with that of 18F-BPA. The SUVmax of 18F-FDG ⩾5.0 is considered to be suggestive of high 18F-BPA accumulation. Conclusions18F-FDG PET might be an effective screening method performed prior to 18F-BPA for selecting patients with head and neck cancer for treatment with BNCT.

Relationship between 18F-FDG accumulation and lactate dehydrogenase A expression in lung adenocarcinomas.

(18)F-FDG PET has been widely used in the management of malignant tumors. Lactate dehydrogenase A (LDHA) plays an important role in the development, invasion, and metastasis of malignancies. However, the relationship between (18)F-FDG accumulation and LDHA expression has not been investigated. Retrospective analysis was conducted for 51 patients with lung adenocarcinomas who underwent (18)F-FDG PET. The relationship between maximum standardized uptake value and the expression of LDHA, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) were examined. RNA interference was used to analyze the role of LDHA in tumor metabolism and growth in A549 cells. The AKT, also known as protein kinase B, pathway was also investigated to evaluate the molecular mechanisms of the relationship between LDHA expression and (18)F-FDG uptake. Maximum standardized uptake value was significantly higher in the LDHA high-expression group than the LDHA low-expression group (P = 0.018). GLUT1 expression in lung adenocarcinomas was positively correlated with (18)F-FDG accumulation and LDHA expression whereas HK2 expression was not. Knockdown of LDHA led to a significant decrease in GLUT1 expression, (18)F-FDG uptake, and cell proliferation. The activated form of AKT was also decreased after LDHA knockdown. LDHA increases (18)F-FDG accumulation into non-small cell lung cancer, possibly by upregulation of GLUT1 expression but not HK2 expression. LDHA may modulate (18)F-FDG uptake in lung adenocarcinomas via the AKT-GLUT1 pathway. These results indicate that (18)F-FDG PET/CT may predict LDHA expression levels and response to anti-LDHA therapy in lung adenocarcinomas.

Small-animal PET demonstrates brain metabolic change after using bevacizumab in a rat model of cerebral ischemic injury.

To evaluate the effect of bevacizumab on cerebral ischemia, we used 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F-FDG) small-animal positron emission tomography (PET) in the middle cerebral artery occlusion (MCAO) rat model. After baseline neurologic function tests and PET studies, MCAO Sprague-Dawley rats received bevacizumab or normal saline (controls). Weekly PET imaging and neurologic function tests showed that the (18)F-FDG accumulation in the bevacizumab group was similar to that in the controls during the first 2 weeks, but lower than in controls at weeks 3 and 4. However, no difference was found in neurological scores between the groups. The number of von Willebrand factor-positive cells in the bevacizumab group was lower than that in controls. The expression of vascular endothelial growth factor was higher than in controls at week 4. These results suggested that bevacizumab does not influence functional recovery in this model of cerebral ischemia during a 4-week period, but inhibits vascular formation and metabolic recovery, which may be considered in cancer patients with a recent ischemic stroke.

Standardized Spatial Heterogeneity of Baseline Intratumoral 18F-FDG Accumulation for Outcome Prediction of Concurrent Chemoradiation Therapy in Cervical Cancer

Standardized Spatial Heterogeneity of Baseline Intratumoral 18F-FDG Accumulation for Outcome Prediction of Concurrent Chemoradiation Therapy in Cervical Cancer