Fluorine-19 NMR imaging of glucose metabolism

Metabolic imaging reflecting glucose metabolism in the glycolytic and aldose reductase sorbitol (ARS) pathways was performed noninvasively in rat using fluorinated glucose analogs, 2-fluoro-2-deoxy-D-glucose (2-FDG) or 3-fluoro-3-deoxy-D-glucose (3-FDG), and fluorine-19 (19F) nuclear magnetic resonance (NMR) imaging. 19F images of 2-FDG-6-phosphate, a main metabolite of 2-FDG in the glycolytic pathway, showed high glucose utilization in the brain, spinal cord, and heart. Images of 3-fluoro-3-deoxy-D-sorbitol (3-FDSL), a main metabolite of 3-FDG in the ARS pathway, demonstrated the heterogeneous nature of the spatial distribution of aldose reductase activities, being highest in the brain and lens. The extremely low toxicity of 3-FDG indicates promise for clinical application of 3-FDG NMR imaging.     

Synthesis and biological evaluation of a fluorine-18-labeled nonsteroidal androgen receptor antagonist, N-(3-[18F]fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide

INTRODUCTION: Androgen receptor (AR), which is overexpressed in most prostate cancers, is the target of androgen ablation and antiandrogen therapies: it is also the target for the receptor-mediated imaging of AR-positive prostate cancer using radiolabeled ligands. Previous AR imaging agents were based on a steroidal core labeled with fluorine. To develop a novel class of nonsteroidal imaging agents, with binding and pharmacological characteristics that are more similar to those of clinically used AR antagonists, we synthesized N-(3-fluoro-4-nitronaphthyl)-cis-5-norbornene-endo-2,3-dicarboxylic imide (3-F-NNDI), an analog of recently reported AR antagonist ligands. METHODS: 3-F-NNDI was synthesized in six steps starting with 1-nitronaphthalene, with fluorine incorporation as the final step. The labeling of 3-F-NNDI with fluorine-18 was achieved through a novel, extremely mild, S(N)Ar displacement reaction of an o-nitro-activated arene trimethylammonium salt, and 3-[(18)F]F-NNDI was prepared in high specific activity. RESULTS AND DISCUSSION: 3-F-NNDI was found to have an AR-binding affinity similar to that of its parent compound. In vitro assays demonstrated high stability of the labeled compound under physiological conditions in buffer and in the blood. Androgen target tissue uptake in diethylstilbestrol-pretreated male rats, however, was minimal, probably because of extensive metabolic defluorination the radiolabeled ligand. CONCLUSIONS: This study is part of our first look at a novel class of nonsteroidal AR antagonists as positron emission tomography (PET) imaging agents that are alternatives to steroidal AR agonist-based imaging agents. Although 3-[(18)F]F-NNDI has significant affinity for AR, it showed limited promise as a PET imaging agent because of its poor target tissue distribution properties.     

Analysis of 2-[Fluorine-18]-Fluoro-2-deoxy-D-glucose uptake kinetics in PET studies of pulmonary inflammation

Dynamic positron emission tomography (PET) imaging of the lung using the radiotracer 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is an emerging method to assess noninvasively the metabolic activity of pulmonary inflammatory cells. Nevertheless, because of the distinct functional and structural characteristics of inflamed lung tissue standard methods of (18)F-FDG analysis can be substantially limited and there is no consensus about the best method for quantification of the (18)F-FDG signal for acute or chronic inflammatory lung diseases. This article gives an overview on recent advances in quantitative analysis of (18)F-FDG uptake kinetics in non-neoplastic inflamed lung tissue.     

Morphologic and functional changes in nontumorous liver tissue after radiofrequency ablation in an in vivo model: comparison of 18F-FDG PET/CT, MRI, ultrasound, and CT.

Rimlike contrast enhancement on morphologic imaging and increased tracer uptake on (18)F-FDG PET in the periphery of the necrosis can hamper differentiation of residual tumor from regenerative tissue after radiofrequency ablation of liver lesions. This study used MRI, CT, ultrasound, and (18)F-FDG PET/CT to assess the typical appearance of lesions in nontumorous animal liver tissue after radiofrequency ablation. METHODS: Lesions were created by radiofrequency ablation of normal liver parenchyma in 21 minipigs. Follow-up was performed by 3 contrast-enhanced morphologic modalities-MRI, CT, and ultrasound-and by (18)F-FDG PET/CT immediately, 3 and 10 d, and 1, 2, 3, and 6 mo after radiofrequency ablation. Images were evaluated qualitatively for areas of increased enhancement and regions of elevated tracer uptake. Furthermore, all images were assessed quantitatively by determination of ratios comparing enhancement/tracer uptake in the periphery of the necrosis with enhancement/tracer uptake in normal liver parenchyma. Imaging findings were compared with histopathology findings. RESULTS: Immediately after radiofrequency ablation, no increase in (18)F-FDG uptake was visible, whereas elevated enhancement was noticed in the periphery of the necrosis on all morphologic imaging procedures. At further follow-up, an area of rimlike increase in (18)F-FDG uptake surrounding the necrosis was detected on PET/CT. The rimlike pattern of increased enhancement in the arterial phase was present for all liver lesions on CT, MRI, and ultrasound, especially between day 3 and month 1 after the radiofrequency ablation. Both elevated glucose metabolism and enhancement persisted for 6 mo postinterventionally. Histologic examination showed a hemorrhagic border converting into a regeneration capsule. CONCLUSION: If performed immediately after radiofrequency ablation, (18)F-FDG PET/CT probably has benefits over those of morphologic imaging procedures when assessing liver tissue for residual tumor. Later follow-up may be hampered by visualization of peripheral hyperperfusion and tissue regeneration. Further studies on a patient population are essential.     

<Superscript>125</Superscript>I-BMIPP and <Superscript>18</Superscript>F-FDG uptake in a transgenic mouse model of stunned myocardium

Reported metabolic patterns in myocardial stunning are not uniform. We investigated relative myocardial perfusion, glucose and fatty acid uptake using a technetium-99 hexakis-2-methoxyisobutyl-isonitrile (MIBI), fluorine-18 2-fluoro-2-deoxyglucose (FDG) and iodine-125 15-(p-iodo-phenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) mixture, in a recently developed transgenic (TR) mouse model which mimics stunned myocardium. Twenty-seven mice - 14 TR and 13 age-matched wild type controls (C) - were divided into four groups: TR-fed, TR-fasted, C-fed and C-fasted. Animals were sacrificed 2 h after injection, tissue samples counted and percent-injected dose/gram tissue (% id/g) calculated for each radioisotope. Tissues were also Folch extracted and 125I incorporation into the various lipid pools (TG, triglycerides; DG, diglycerides; FFA, free fatty acids; PL, phospholipids) was determined by thin-layer chromatography (TLC). The pooled data for each of the four groups (TR-fed vs C-fed and TR-fed vs C-fasted) showed no differences in myocardial blood flow (% MIBI id/g), glucose uptake (% FDG id/g) or fatty acid uptake (% BMIPP id/g). Only minor differences were observed in the incorporation of 125I-BMIPP into the myocardial TG, DG, FFA and PL lipid pools. However, significantly decreased myocardial FDG uptake was observed in a subset of fasted mice - four out of ten TR-fasted mice (3.4% vs 20.5% id/g) and three out of nine C-fasted mice (5.5% vs 30.6% id/g). The transgenic mouse model of stunned myocardium shows normal myocardial perfusion and overall intact myocardial glucose and myocardial fatty acid uptake as determined with clinically applicable radiolabelled analogues. These data are in line with the hypothesis that the contractile inefficiency in stunned myocardium is not linked to metabolic alterations but is associated with an insufficient chemical to mechanical energy coupling.     

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.

While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment.     

14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA): evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids

14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (FTHA) is a new radiolabeled long-chain fatty acid (LCFA) analog designed to undergo metabolic trapping subsequent to its commitment to the beta-oxidation pathway. Sulfur-substitution at the sixth carbon of FTHA causes a prolonging of myocardial clearance half-time (T 1/2 approximately 2 hr) in mice with little diminution of myocardial uptake (39.8 +/- 3.0% ID/g at 5 min). Heart-to-blood ratios were 20 +/- 6 and 82 +/- 16 at 1 and 60 min, respectively. In contrast, the 3-thia analog, 13(R,S)-[18F]-fluoro-3-thia-hexadecanoic acid, showed lower uptake and poor retention by heart. Myocardial uptake of FTHA was reduced by 81% (p less than 10(-5) and 87% (p less than 5 x 10(-4] in mice pretreated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) at 1 and 60 min, respectively. Radioanalytical studies showed the major metabolic fate of FTHA in control and POCA treated myocardium to be unidentified metabolite(s) that bind to tissue protein. Smaller amounts of 18F radioactivity were present in myocardium as complex lipids, fatty acid, and unidentified soluble metabolites. The results indicate metabolic trapping of FTHA in myocardium subsequent to its entry into the mitochondrion and encourage its further evaluation as a PET tracer of myocardial LCFA utilization.     

FDG PET scan in a primitive neuroectodermal tumor

Primitive peripheral neuroectodermal tumor (PNET) is a rare tumor that often arises in soft tissue. Magnetic resonance imaging is a good diagnostic tool that can establish the extent of disease. The utility of positron emission tomography (PET) using F-18-fluoro-2-deoxy-D-glucose (FDG) in the diagnostic work-up and staging of PNET has not been well established. We present a case of PNET of the right upper extremity that did not show FDG uptake despite its large size and aggressive nature.     

True tracers: comparing FDG with glucose and FLT with thymidine

As PET metabolic imaging becomes routine in clinical practice, there is a tendency to make imaging and data analysis fast and simple, but interpretation of these pictures by visual inspection does not do justice to the power of PET technology. Tissue data and blood data can be analyzed mathematically to provide parametric images of the PET tracer's biochemistry in terms of a transport parameter and a metabolic flux. The methods for parametric imaging with (11)C tracers of glucose and thymidine have been validated, but the short half-life of this radionuclide and the rapid metabolism of these labeled substrates to [(11)C]CO(2) have led investigators to develop (18)F analogs. While (18)F substitution at critical positions in the natural substrate can block metabolism, it has other effects on the transport and metabolism of the analog tracer. The fidelity with which analog tracers mimic tracers of the authentic substrate is critically evaluated for [(18)F]-2-fluoro-2-deoxyglucose and [(18)F]-3'-fluoro-3'-deoxythymidine.     

Discrepant uptake between fluorine-18 fluorodeoxy glucose and Tc-99m sestamibi in bronchioloalveolar cell carcinoma

Several studies have shown the benefit of fluorine-18 fluorodeoxy glucose (FDG) imaging in the differentiation of solitary pulmonary nodules. The majority of malignant tumor have a higher glucose metabolic rate as compared to benign lesions. However, there is a considerable variety in glucose metabolic rate that depends on the aggressiveness and histological subtype of the tumor. Technetium-99m sestamibi (MIBI) is another tumor imaging agent for SPECT. We present a case of bronchioloalveolar cell carcinoma with a false negative finding in FDG imaging and a positive finding in MIBI imaging. This case clearly indicates that the FDG uptake and MIBI uptake might provide different information regarding characteristics of lung cancer.     

Asymmetrical FDG-PET and MRI findings of striatonigral system in multiple system atrophy with hemiparkinsonism.

The asymmetry of the local cerebral metabolic rate for glucose (lCMRglc) and magnetic resonance (MR) imaging was studied in five patients with multiple system atrophy (MSA) presenting hemiparkinsonism. lCMRglc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET) in these patients and five normal control subjects. MR images were obtained in five patients and 11 control subjects. In all patients, T2-weighted MR images showed hypointense areas in the posterior lateral putamen. They were bigger or lower in intensity on the contralateral side than on the ipsilateral side. Significant glucose hypometabolism was found in the posterior putamen on the contralateral side to hemiparkinsonism. A significant decrease in size was found in the contralateral putamen, caudate nucleus, and pars compacta of the substantia nigra. However, no significant correlation was seen between PET and MRI data. In the control subjects, no apparent asymmetry was observed. PET and MR imaging demonstrated the characteristic asymmetry corresponding to the pathological findings reported in MSA.     

Uptake of FDG (2-fluoro-2-deoxy-D-glucose) as a tumor imaging agent into erythrocytes and accumulation of FDG in tumor cells

Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) injectable was developed as a tumor imaging agent reflecting glucose metabolism. In membrane transportation studies, the uptake of 14C-FDG into erythrocytes decreased with an increase in glucose concentration, and Cytochalasin B, inhibitor of glucose transporter (GLUT), blocked the uptake about 75%. The results means FDG is transported into tumor cells mainly by GLUT as glucose analogues. 18F-FDG is recognized to be phosphorylated to 18F-FDG-6-phosphate with hexokinase. We found that FDG-6-phosphate was further isomerized to 18F-FDM-6-phosphate by phosphoglucose isomerase (PGI) in vitro. About 27% 18F-FDM-6-phosphate was generated at the reaction with 70 U PGI for 90 min. These results show that the 18F-FDG injectable manufactured by the commercial supply system has equivalent properties; membrane transportation characteristic and enzyme affinity, to FDG synthesized at each PET institution.     

新生儿脑18F-FDG PET显像初步研究

目的 观察部分新生儿肺炎患儿和早产儿的脑^18F-脱氧葡萄糖（FDG）PET显像图,从代谢角度分析其脑功能.方法 对9例新生儿肺炎患儿及7例早产儿行脑^18F-FDG PET检查.结果 新生儿正常脑^18F-FDG PET影像与成人及儿童明显不同,整个脑的结构不清晰,其葡萄糖代谢活性区主要集中在丘脑、小脑、感觉运动皮质、基底节等脑组织,其中丘脑摄取^18F-FDG最多,大脑皮质摄取^18F-FDG的量较低.分别用1、2、3 min的透射采集作衰减校正,所得图像质量无明显差异.结论 脑^18F-FDG PET显像可作为研究新生儿脑功能代谢行之有效的方法之一.对新生儿行脑^18F-FDGPET显像应尽量减少透射采集时间.     

False-positive uptake on 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography/computed tomography (PET/CT) in oncological imaging

With the increasing utilization of integrated positron-emission tomography/computed tomography (PET/CT) using the glucose analogue 2-[1?F]-fluoro-2-deoxy-D-glucose (FDG) in oncological imaging, it is important for radiologists and nuclear medicine physicians to be aware that FDG uptake is not specific for malignancy, as many different physiological variants and benign pathological conditions can also exhibit increased glucose metabolism. Such false-positive FDG uptake often arises outside the area of primary interest and may mimic malignant disease, thereby confounding accurate interpretation of PET/CT studies. With the use of illustrative clinical cases, this article will provide a systematic overview of potential interpretative pitfalls and illustrate how such unexpected findings can be appropriately evaluated.     

Serum glucose: effects on tumor and normal tissue accumulation of 2-[F-18]-fluoro-2-deoxy-D-glucose in rodents with mammary carcinoma.

The positron-emitter-labeled glucose analogue 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) accumulates into many cancers after intravenous injection, but the effect of serum glucose levels on FDG uptake in the tumor has not been extensively studied. In vitro, elevated media glucose levels markedly diminished FDG and FDG 6-phosphate uptake and retention in human adenocarcinoma cells, while insulin had no effect. Mammary cancers were established subcutaneously in 12 rats. Six control rats with mammary tumors were fasted overnight. Hyperglycemia was established in six rats by means of continuous glucose infusion (glucose clamp). All animals were then intravenously administered 50 microCi of FDG. Serum glucose levels were 87 mg/dL (4.83 mmol/L) in the control animals and more than 900 mg/dL (49.9 mmol/L) in the hyperglycemic animals. One hour after injection of FDG, mean F-18 uptake in the tumor, brain, small bowel, and ovaries was 2.7-9.7 times lower in the hyperglycemic animals (P less than .02). Mean F-18 activity in the kidneys tended to be somewhat higher in the hyperglycemic animals. FDG uptake in other tissues was comparable between the control and hyperglycemic groups. These data suggest that high serum glucose levels may substantially impair visceral tumor imaging with FDG positron emission tomography.     

MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, ¹⁸F-FDG and ¹¹C-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 μg dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, N = 18), Group B (DES, no-DHT, N = 18) and Group C (DES, DHT, N = 18). In each group, 10 animals received ¹⁸F-FDG, whereas the remaining eight animals were administered ¹¹C-acetate. Rats were sacrificed at 120 min post-injection of ¹⁸F-FDG or 30 min post-injection of ¹¹C-acetate. Pretreatment of the mouse model using DHT (200 μg of DHT in 0.1 mL of sunflower seed oil) or DES (200 μg of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in ¹⁸F-FDG study, while there was no significant difference in ¹¹C-acetate uptake. These results indicate that changes in serum testosterone levels influence ¹⁸F-FDG uptake in the prostate gland, which is closely tied to glucose metabolism, within 24 hours of treatment and in the prostate tumor within 1 week. These early metabolic changes could enable monitoring metabolic changes in prostate tumor following treatment by imaging using ¹⁸F-FDG PET. Further studies are needed to clarify the reason for the insensitivity of ¹¹C-acetate for measuring metabolic change in prostate tumor.     

Assessment of liver tissue after radiofrequency ablation: findings with different imaging procedures.

Our goal was to assess the typical appearance of normal liver tissue immediately after radiofrequency ablation (RF-ablation) when imaged with contrast-enhanced ultrasound, CT, MRI, 18F-FDG PET, and PET/CT. METHODS: Nineteen RF-ablation sessions were performed on nontumorous liver tissue of 10 G?ttingen Mini Pigs. CT, ultrasound, MRI, 18F-FDG PET, and PET/CT were performed immediately after the intervention. All imaging procedures were evaluated qualitatively for areas of increased contrast enhancement (morphologic imaging) and regions of elevated tracer uptake (functional imaging). Images were assessed quantitatively by determination of ratios (r(p/p)) comparing contrast enhancement/tracer uptake in the periphery of the necrosis with contrast enhancement/tracer uptake of normal liver parenchyma. RESULTS: On morphologic imaging, an increase in contrast enhancement surrounding the ablative necrosis was detected in all lesions. Quantification of this area of increased contrast enhancement revealed ratios of r(p/p) = 1.57 +/- 0.2 for CT and r(p/p) = 1.57 +/- 0.19 for MRI. On PET and PET/CT, homogeneous tracer utilization was found surrounding all lesions. There were no areas of a focal or rim-like increase in glucose metabolism. The ratio r(p/p) was found to be 1.05 +/- 0.08 for functional data. Histologic examination revealed pooling of blood in the sinusoids of the lesion's periphery that was caused by outflow obstruction due to the central necrosis. CONCLUSION: On morphologic imaging, a rim-like increase of contrast enhancement was found immediately after RF-ablation resembling peripheral hyperperfusion. This area of contrast enhancement may hamper detection of residual tumor. On the basis of homogeneous tracer distribution surrounding the area of necrosis, PET and PET/CT may serve for early assessment of patients after RF-ablation.     

18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors.

Because of the high glucose metabolism in normal brain tissue 18F-FDG is not the ideal tracer for the detection of gliomas. Methyl-11C-l-methionine (11C-MET) is better suited for imaging the extent of gliomas, because it is transported specifically into tumors but only insignificantly into normal brain. 3'-Deoxy-3'-18F-fluorothymidine (18F-FLT) has been introduced as a proliferation marker in a variety of neoplasias and has promising potential for the detection of brain tumors, because its uptake in normal brain is low. Additionally, the longer half-life might permit differentiation between transport and intracellular phosphorylation. METHODS: PET of 18F-FLT and 11C-MET was performed on 23 patients (age range, 20-70 y) with histologically verified gliomas of different grades. On all patients, conventional MRI was performed, and 16 patients additionally underwent contrast-enhanced imaging. Images were coregistered, and the volumes of abnormality were defined for PET and MRI. Uptake ratios and standardized uptake values (SUVs) of various tumors and regions were assessed by region-of-interest analysis. Kinetic modeling was performed on 14 patients for regional time-activity curves of 18F-FLT from tumorous and normal brain tissue. RESULTS: Sensitivity for the detection of tumors was lower for 18F-FLT than for 11C-MET (78.3% vs. 91.3%), especially for low-grade astrocytomas. Tumor volumes detected by 18F-FLT and 11C-MET were larger than tumor regions displaying gadolinium enhancement (P<0.01). Uptake ratios of 18F-FLT were higher than uptake ratios of 11C-MET (P<0.01). Uptake ratios of 18F-FLT were higher in glioblastomas than in astrocytomas (P<0.01). Absolute radiotracer uptake of 18F-FLT was low and significantly lower than that of 11C-MET (SUV, 1.3+/-0.7 vs. 3.1+/-1.0; P<0.01). Some tumor regions were detected only by either 18F-FLT (7 patients) or 11C-MET (13 patients). Kinetic modeling revealed that 18F-FLT uptake in tumor tissue seems to be predominantly due to elevated transport and net influx. However, a moderate correlation was found between uptake ratio and phosphorylation rate k3 (r=0.65 and P=0.01 for grade II-IV gliomas; r=0.76 and P<0.01 for grade III-IV tumors). CONCLUSION: 18F-FLT is a promising tracer for the detection and characterization of primary central nervous system tumors and might help to differentiate between low- and high-grade gliomas. 18F-FLT uptake is mainly due to increased transport, but irreversible incorporation by phosphorylation might also contribute. In some tumors and tumor areas, 18F-FLT uptake is not related to 11C-MET uptake. In view of the high sensitivity and specificity of 11C-MET PET for imaging of gliomas, it cannot be excluded that 18F-FLT PET was false positive in these areas. However, the discrepancies observed for the various imaging modalities (18F-FLT and 11C-MET PET as well as gadolinium-enhanced MRI) yield complementary information on the activity and the extent of gliomas and might improve early evaluation of treatment effects, especially in patients with high-grade gliomas. Further studies are needed, including coregistered histology and kinetic analysis in patients undergoing chemotherapy.     

Evaluation of treatment response to radiotherapy in head and neck cancer with fluorine-18 fluorodeoxyglucose

Nineteen patients with malignant head and neck tumors were imaged before and during radiation therapy with 18F-2-fluoro-2-deoxy-D-glucose (FDG) to study the effect of radiotherapy (RT) on FDG uptake. All tumor images were FDG-positive before treatment. After RT, a decrement of tumor FDG uptake was found in all but two patients; these were nonradioresponders. There was a significant decrement (p less than 0.001) in uptake ratios after irradiation of 30 +/- 5 Gy among the radioresponsive (CR + PR) but not among the radioresistant (NC + PD) tumors. The administered dose of RT correlated (r = 0.47, p less than 0.05) with the decrement in FDG activity among the CR + PR but not among the NC + PD patients. The biologic half-life of FDG radioactivity in tumor tissue was evaluated by dynamic scintigraphy. A change in the half-life of FDG toward the value observed in normal tissue was associated with treatment response. The results suggest that FDG imaging can be used for follow-up of RT in patients with head and neck cancer.     

Adrenal neoplasms

Adenoma, myelolipoma, phaeochromocytoma, metastases, adrenocortical carcinoma, neuroblastoma, and lymphoma account for the majority of adrenal neoplasms that are encountered in clinical practice. A variety of imaging methods are available for evaluating adrenal lesions including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine techniques such as meta-iodobenzylguanidine (MIBG) scintigraphy and positron-emission tomography (PET). Lipid-sensitive imaging techniques such as unenhanced CT and chemical shift MRI enable detection and characterization of lipid-rich adenomas based on an unenhanced CT attenuation of ≤10?HU and signal loss on opposed-phase compared to in-phase T1-weighted images, respectively. In indeterminate cases, an adrenal CT washout study may differentiate adenomas (both lipid-rich and lipid-poor) from other adrenal neoplasms based on an absolute percentage washout of >60% and/or a relative percentage washout of >40%. This is based on the principle that adenomas show rapid contrast washout while most other adrenal neoplasms including malignant tumours show slow contrast washout instead. (18)F-2-fluoro-2-deoxy-d-glucose-PET ((18)FDG-PET) imaging may differentiate benign from malignant adrenal neoplasms by demonstrating high tracer uptake in malignant neoplasms based on the increased glucose utilization and metabolic activity found in most of these malignancies. In this review, the multi-modality imaging appearances of adrenal neoplasms are discussed and illustrated. Key imaging findings that facilitate lesion characterization and differentiation are emphasized. Awareness of these imaging findings is essential for improving diagnostic confidence and for reducing misinterpretation errors.