Biodistribution Of 18F-FDG Research Articles

Steroid-Induced Activated White Adipose Tissue Detected on 18F-FDG PET/CT.

White adipose tissue (WAT) usually shows negligible 18F-FDG uptake due to negligible glucose utilization. However, corticosteroids alter the biodistribution of 18F-FDG and increase uptake in WAT. Here, we present a case of diffusely increased 18F-FDG uptake in WAT secondary to high-dose corticosteroid therapy for nephrotic syndrome.

Various Aspects of Fasting on the Biodistribution of Radiopharmaceuticals.

It is demonstrated that fasting can alter the biodistribution of radiopharmaceuticals in nuclear medicine. Various studies have highlighted that fasting is interpreted to be easy for physicians during PET study, fasting is one of the most important factors determining the usefulness of this protocol. It is well documented that fasting can suppress normal 18F-FDG PET uptake during nuclear cardiology. However, there is no consensus about the usefulness of fasting on radiopharmaceuticals, especially on 18F-FDG in PET imaging, but special attention should be paid to the setting of the fasting duration. Nevertheless, it does seem we still need extensive clinical studies in the future. The present study aims to review the various aspects of fasting, especially metabolic alteration on radiopharmaceutical biodistribution. In this study, we focused more on the effect of fasting on 18F-FDG biodistribution, which alters its imaging contrast in cardiology and cancer imaging. Therefore, shifting substrate metabolism from glucose to free fatty acids during fasting can be an alternative approach to suppress physiological myocardial uptake.

Impact of Blood Glucose Level on Biodistribution of 18F-FDG in Brain for the Assessment of Neurodegenerative Disorders

Purpose: Hyperglycemia have effect on the FDG uptake in the brain, potentially mimic the patterns seen in early neurodegenerative disease in normal individuals. Therefore, in this study, the impact of blood glucose level on the cerebral uptake of 18F-FDG was evaluated and establish suitable blood glucose level cutoff for the assessment of neurodegenerative disorders.

Evaluation of doxorubicin-induced early multi-organ toxicity in male CD1 mice by biodistribution of 18F-FDG and 67Ga-citrate. Pilot study

The search for methods that identify early toxicity, induced by chemotherapy, is urgent. Changes in the biodistribution of radiopharmaceuticals could give information on early toxicity. Ten-week-old CD1 male mice were divided into four groups. Two groups were administered a weekly dose of 5 mg/kg of doxorubicin hydrochloride (DOX) for 5 weeks and the control groups were administered saline solution. One week after the end of treatment, the biodistribution of 18F-FDG and 67Ga-citrate were carried out, as was the quantification of plasma enzymes CK, CK-MB, LDH and AST. All enzymes were higher in the treated animals, but only significant (p < 0.05) in the case of CK-MB. 18F-FDG uptake increased in all organs of treated animals except retroperitoneal fat, being significant in spleen, brain, heart, liver, lung, kidney, and inguinal fat. 67Ga-citrate had a more complex pattern. The uptake in the DOX group was higher in spleen, lung, kidney, testes, and gonadal fat, it did not change in brain, heart, and liver, and it was lower in the rest of the organs. It only showed significant differences in lung and pancreas. A thorough discussion of the possible causes that produced the change in biodistributions of both radiopharmaceuticals is included. The pilot study showed that both radiopharmaceuticals could identify early multi-organ toxicity induced by DOX. Although 18F-FDG seems to be better, 67Ga-citrato should not be ruled out a priori. The detection of early toxicity would serve to adopt treatments that prevent its progression, thus improving patient’s quality of life.

Oncologic significance of unexpected osseous foci on FDG-PET without correlative CT abnormalities.

Our purpose was to explore the clinical significance of unexpected osseous foci on 18F-FDG-PET without correlative CT abnormalities (FWCT) in patients referred for oncologic evaluation. The significance of FDG-avid foci without correlative CT abnormalities has been previously explored in tissues such as breast, lung, liver, and prostate; however, osseous foci without correlative CT abnormalities continue to present challenges in diagnostic interpretations. This study is a retrospective review of 120 osseous FWCT, reported in 91 patients, and their corresponding clinical follow-up. We included only patients with at least 6months of clinical follow-up leading to a final diagnosis, reviewing bone biopsy results, follow-up imaging, and clinical notes. We excluded those patients on active chemotherapy at the time of the scan. For reports describing > 3 foci, we only analyzed the one with highest maximum standardized uptake value (SUVmax). As a measure of uptake intensity, we obtained focus-to-liver ratios (F/L) utilizing their SUVmax and corresponding hepatic 3D SUVmean. Of 91 patients, 74 (81%) had biopsy-confirmed primary malignancies and 17 (19%) had suspicious findings on diagnostic imaging, but no proven primary malignancy. 50 of 120 (42%) osseous foci were malignant and 70 (58%) were benign. 49 of 120 (41%) foci were solitary and 71 (59%) were 0 with other foci (non-solitary). Malignancy resulted from 15/49 (31%) solitary foci and 35/71 (49%) non-solitary foci. Malignant lesions had a mean F/L 2.37 ± 0.397 and benign lesions a mean F/L 1.49 ± 0.169. Osseous malignancy correlated with a higher uptake intensity (Spearman = 0.408; P < 0.01) and was significantly associated with F/L ≥ 2.0 (P < 0.001). Osseous FWCT led to restaging and management modification in 12/91 (13%) patients. Osseous FWCT frequently represent early stages of malignancy. A higher index of suspicion is warranted for osseous FWCT associated with underlying myeloproliferative neoplasms, breast and lung cancer, and moderate (F/L 1.0-2.0) or high (F/L > 2.0) uptake intensity. Interpreting physicians encountering these variables can recommend interval follow-up with 18F-FDG-PET/CT or correlation with contrast-enhanced MRI or tissue biopsy. In patients with an altered biodistribution of 18F-FDG in the bone marrow (e.g., recent chemotherapy cycle), follow-up FDG-PET can be obtained at an appropriate time interval following oncologic treatment.

Comprehensive analysis of the influence of G-CSF on the biodistribution of 18F-FDG in lymphoma patients: insights for PET/CT scheduling

Aims(1) To perform a comprehensive analysis of the time elapsed between the last G-CSF injection and the PET/CT examination on the biodistribution of 18F-FDG, with emphasis on liver, spleen, and bone marrow uptake, and (2) to investigate whether an inversion of the liver to spleen ratio affects the Deauville scoring.Materials and methodsRetrospectively included were 74 consecutive diffuse large B cell lymphoma (DLBCL) patients referred for baseline and interim examinations and receiving immunochemotherapy with various G-CSF regimens. A comprehensive evaluation considering baseline metabolic active tumour volume (MATV), factors affecting liver uptake, the type of G-CSF, and the time elapsed between chemotherapy/G-CSF and interim PET/CTs was performed.ResultsMean (± SD) percentage variations between baseline and interim PET/CTs (i-PET/CT) for bone marrow (%Variation_BONE), liver (%Variation_LIVER) and spleen (%Variation_SPLEEN) were equal to 32.0 ± 46.9%, 16.1 ± 42.8%, and 10.6 ± 51.1 %, respectively. %Variation_LIVER and %Variation_SPLEEN were higher in patients using lenograstim, but this was linked to lower uptakes at baseline and was therefore likely not due to G-CSF itself. The mean delay between G-CSF injection and i-PET/CT acquisition was not an independent explanatory variable for %Variation_BONE, %Variation_LIVER, and %Variation_SPLEEN. On the contrary, %Variation_BONE and %Variation_SPLEEN were negatively correlated to the time-lapse between the end of chemotherapy and i-PET/CT: ρ = − 0.342 (p = 0.010) and ρ = − 0.529 (p < 0.0001), respectively. Patients with a time-lapse since the last injection of chemotherapy < 17 days displayed higher bone and spleen SUVmaxEARL. %Variation_LIVER was positively correlated to baseline MATV: ρ = 0.243 (p = 0.039). Patients displaying a high baseline MATV ≥ 177 cc had significantly lower liver SUVmaxEARL at baseline. This difference was no longer observed at i-PET/CT, after tumours had shrunk.ConclusionsNeither the type of G-CSF used nor the time elapsed between its last injection and i-PET/CT examination independently influences bone, hepatic, or splenic uptakes at i-PET/CT. The major determinant for the occurrence of a bone or spleen hypermetabolism on i-PET/CT is the time elapsed between the chemotherapy and the examination, which should be maintained above 15 days. Inversion of the liver to spleen ratio appeared to be due to increased spleen hypermetabolism on i-PET/CT, making unlikely an impact on the Deauville scoring.

Sex differences in the effects of acute stress on cerebral glucose metabolism: A microPET study

Stress has been considered as a risk factor for the development and aggravation of several diseases. The hypothalamic-pituitary-adrenal axis (HPA) is one of the main actors for the stress response and homeostasis maintenance. Positron emission tomography (PET) has been used to evaluate neuronal activity and to study brain regions that may be related to the HPA axis response. Since neuroimaging is an important tool in detecting neuroendocrine-related changes, we used fluorodeoxyglucose-18 (18F-FDG) and positron emission microtomography (microPET) to evaluate sexual differences in the glucose brain metabolism after 10, 30 and 40 min of acute stress in Balb/c mice. We also investigated the effects of restraint stress in blood, liver and adrenal gland 18F-FDG biodistribution using a gamma counter. A decreased glucose uptake in the whole brain in both females and males was found. Additionally, there were time and sex-dependent alterations in the 18F-FDG uptake after restraint stress in specific brain regions, indicating that males could be more vulnerable to the short-term effects of acute stress. According to the gamma counter biodistribution, only females showed a significant decreased glucose uptake in the blood, liver and right adrenal after restraint stress. In addition, in comparisons between the sexes, males showed a decreased glucose uptake in the whole brain and in several brain regions compared to females. In conclusion, exposure to acute restraint stress resulted in significant decreased glucose metabolism in the brain, with particular effects in different regions and organs in a sex-specific manner.

Monitoring internal contamination from OEW of an 18F-FDG production plant: WBC or head counting setup?

The production 18F-FDG for positron emission tomography (PET) has consistently increased over the past two decades. The risk of internal contamination at 18F-FDG production facilities exists. A setup for evaluation of the 18F-FDG activity incorporated into the OEW brain, called Head Counting System (HCS), was presented in previous works. In this study, the whole body counter setup (WBC) was evaluated for monitoring 18F incorporations. The Monte Carlo Virtual Software (VMC in-vivo) and the MCNPx code were used to assess the system calibration coefficient (CC). Three 18F distributions were simulated: i) uniformly distributed in soft tissue (UDST); ii) Na18F biodistribution (NAFB); and iii) 18F-FDG biodistribution (FDGB). The calibration coefficient of WBC was compared to the current head counting system CC under the same biodistribution conditions. The ICRP male reference voxelized phantoms (RCP_AM) was used in the simulations. The results showed that the WBC setup was more efficient than the head counter for all the studied 18F distributions: UDST = 1060 %, FDGB = 488 % and NAFB = 340 %. Despite this, especially for 18F-FDG, the possibility of bladder voiding before measurement can lead to considerable uncertainties when the WBC setup is used. On the other hand, bladder activity does not show great influence the calibration coefficient of the head counting system. Future work will evaluate the WBC sources of uncertainties in the measurement of 18F incorporated activity.

Sex as a Biologic Variable in Preclinical Imaging Research: Initial Observations with 18F-FLT.

The study objective was to investigate whether sex influences 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) uptake and tissue distribution in mouse models of cancer. Methods:18F-FLT biodistribution was measured in 3 strains of male and female mice (129S6/SvEv, athymic nude, and BALB/c). 18F-FDG biodistribution was measured for comparison. 18F-FLT uptake was also measured in female 129S6/SvEv mice bearing estrogen-dependent SSM3 mouse mammary tumors, male athymic nude mice bearing androgen-dependent CWR22 prostate cancer xenografts, and male and female athymic nude mice bearing estrogen-independent MDA-MB-231 human breast cancer xenografts. Ki-67 expression was assayed by immunohistochemistry. PET/CT imaging was performed to visualize 18F-FLT biodistribution and to determine pharmacokinetics. Results: Greater 18F-FLT activity was observed in blood, liver, muscle, heart, kidney, and bone in female than male mice. Pharmacokinetic analysis demonstrated higher early renal 18F-FLT activity and greater accumulation of 18F-FLT in the urinary bladder in male than female mice. The differential pattern of 18F-FLT biodistribution between the sexes seen with 18F-FLT was not observed with 18F-FDG. Increased tumoral 18F-FLT uptake compared with muscle was observed in both the SSM3 mammary tumors (2.4 ± 0.17 vs. 1.6 ± 0.14 percentage injected dose [%ID]/g at 2 h after injection, P = 0.006) and the CWR22 prostate cancer xenografts (0.34 ± 0.08 vs. 0.098 ± 0.033 %ID/g at 2 h after injection, P = 0.03). However, because of higher nonspecific muscle uptake in female mice, tumor-to-muscle uptake ratios were greater for CWR22 tumors than for SSM3 tumors (4.2 ± 0.78 vs. 1.5 ± 0.049 at 2 h after injection, P = 0.008). Sex-dependent differences in 18F-FLT uptake were also observed for MDA-MB-231 xenografts (tumor-to-muscle ratio, 7.2 ± 0.9 for female vs. 16.9 ± 8.6 for male, P = 0.039). Conversely, greater tumoral Ki-67 staining was observed in female mice (71% ± 3% for female vs. 54% ± 2% for male, P = 0.009), and this finding more closely matched the relative differences in absolute 18F-FLT tumor uptake values (4.5 ± 0.99 %ID/g for female vs. 1.9 ± 0.30 %ID/g for male, P = 0.03). Conclusion: Depending on whether female or male mice are used, differences in biodistribution and nonspecific tissue uptake can adversely affect quantitative measures of 18F-FLT uptake. Thus, sex is a potential variable to consider in defining quantitative imaging metrics using 18F-FLT to assess tumor proliferation.

Effect of Toxoplasma gondii infection on glucose metabolism in the brain of pregnant rats by [18F]FDG microPET imaging

Toxoplasma gondii (T. gondii) is a pathogenic protozoan parasite, infection of which in early pregnancy increases the risk of serious sequelae in fetus. The aim of this study is to investigate the effect of T. gondii infection on glucose metabolism in the brain of pregnant rats by microPET using 18F-fluorodeoxygulcose (18F-FDG) as the tracer. Thirty female SD rats were divided into the T. gondii infection and control group. After set for pregnancy, the body weight was assessed, T. gondii infection was identified by PCR, ELISA technology and immunohistochemistry, and glucose metabolism in brain of rats was monitored by microPET scan. Our results showed that brain glucose metabolism was significantly increased in T. gondii-infected group comparing to the control, indicating microPET scan is more sensitive to detect the abnormality than traditional measurements. In addition, bio-distribution of 18F-FDG in T. gondii-infected rats was assessed by using another twenty female SD rats, which has higher uptake of 18F-FDG at 30 min after injection in whole brain. Furthermore, the expression profile of GLUT1 was also higher in the brain of pregnant rats of the infected group. Therefore, microPET can be effectively applied to in vivo assessment of small animals and contributes to early diagnosis of T. gondii infection, which also assists in understanding birth defects caused by T. gondii infection.

Normal conus medullaris FDG uptake in children

The biodistribution of 18F-FDG has been well described in both adults and children. Many findings are limited to children and warrant understanding prior to interpretation. To determine the normal level of conus medullaris uptake, not previously reported in the literature to date, in a series of consecutive FDG PET/CT scans performed in children. With IRB approval, we retrospectively reviewed 100 consecutive whole-body pediatric 18F-FDG PET/CT examinations obtained for various clinical indications. Scans that showed visible uptake of FDG at the conus were objectively evaluated, and standardized uptake value (SUV) was determined. Maximum SUV of the conus was compared to background, normal liver and lung, and ratios were recorded. Pathology in the conus was excluded. The scans of 100 patients ages 5 months to 24 years (mean 11.7 years) were reviewed. Three patients were excluded. Seventy percent showed uptake at the conus medullaris. SUVs ranged from 1.33 to 4.2 (mean 2.14). Low-level 18F-FDG uptake is common in the conus medullaris, represents normal distribution in children and should not be interpreted as metastatic disease to the CNS.

Rapid Reduction of 1-Receptor Binding and 18F-FDG Uptake in Rat Gliomas After In Vivo Treatment with Doxorubicin

Sigma-receptors are strongly overexpressed in most rodent and human tumors and are proliferation markers. To evaluate the potential of a radiolabeled sigma1-ligand for therapy monitoring, we compared early changes of 11C-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine (11C-SA4503) binding and 18F-FDG uptake in gliomas after in vivo chemotherapy. C6 cells (2.5 x 10(6)) were subcutaneously injected into the right shoulder of male Wistar rats. After 7 d, the tumor volume was 0.60 +/- 0.08 cm3. Animals then received either saline or doxorubicin (8 mg/kg, intraperitoneally). One control and 1 treated rat were imaged simultaneously, 24 or 48 h after treatment, under pentobarbital anesthesia. Rodents (n = 20) were scanned first with 11C-SA4503 (25 MBq, intravenously) followed more than 100 min afterward by 18F-FDG (20 MBq, intravenously), using a dedicated small-animal PET camera (60-min protocol, tumors in the field of view). Tumor homogenates were prepared and subjected to sigma-receptor assays. The biodistribution of 18F-FDG was assessed. Tumors appeared 4-5 d after inoculation and grew exponentially. No significant reduction of tumor growth was visible within 48 h after doxorubicin treatment. Both PET tracers visualized the tumors and showed reduced uptake after chemotherapy (11C-SA4503: 26.5% +/- 6.5% at 24 h, 26.5% +/- 7.5% at 48 h; 18F-FDG: 22.6% +/- 3.2% at 24 h, 27.4% +/- 3.2% at 48 h; ex vivo 18F-FDG: 22.4% +/- 5.4% at 24 h, 31.7% +/- 12.7% at 48 h). Sigma1-receptor density in treated tumors was also reduced (from 172 +/- 35 to 125 +/- 28 fmol/mg of protein). Both 11C-SA4503 binding and 18F-FDG uptake declined in gliomas after chemotherapy. Decreased binding of 11C-SA4503 corresponded to a loss of sigma1-receptors from the tumors. Changes in tracer uptake preceded the morphologic changes by at least 48 h.

Paediatric oncology: role of18F-fluorodeoxyglucose positron emission tomography/computerized tomography

This review deals with the usefulness of combined 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) imaging for the diagnosis and follow-up of extracranial paediatric tumours. After a discussion of the pathophysiologic biodistribution of 18F-FDG, the main indications for 18F-FDG PET/CT imaging in paediatric malignancies are outlined. Moreover, the normal variants of physiologic biodistribution of 18F-FDG and its potential related pitfalls are pointed out.

18F-FDG PET/CT fusion imaging in paediatric solid extracranial tumours

This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of paediatric solid extracranial tumours. Following a brief discussion of the basic principles and methodology of PET/CT system, it reviews the main characteristics of the tumours that can be visualised with 18F-FDG PET and presents examples of cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the management of patients. It will also discuss the physiologic biodistribution of 18F-FDG, outlining the normal variants in the paediatric patients that may lead to misinterpretation.