Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing RANKL/OPG ratio and depressing the TLR4/MyD88 signaling pathway.

Periodontitis (PD) is an inflammatory disease characterized by gingival inflammation and resorption of alveolar bone. Impaired receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) signaling caused by enhanced production of pro-inflammatory cytokines plays an essential role in the pathogenesis of PD. Considering melatonin possesses significant anti-inflammatory property, this study aimed to determine whether prophylactic treatment with melatonin would effectively normalize RANKL/OPG signaling, depress toll-like receptor 4/myeloid differentiation factor 88 (TLR4/MyD88)-mediated pro-inflammatory cytokine activation, and successfully suppress the pathogenesis of PD. PD was induced in adult rats by placing the ligature at molar subgingival regions. Fourteen days before PD induction, 10, 50, or 100 mg/kg of melatonin was intraperitoneally injected for consecutive 28 days. Biochemical and enzyme-linked immunosorbent assay were used to detect TLR4/MyD88 activity, RANKL, OPG, interleukin 1ß, interleukin 6, and tumor necrosis factor-α levels, respectively. The extent of bone loss, bone mineral intensity, and calcium intensity was further evaluated by scanning electron microscopy, micro-computed tomography, and energy-dispersive X-ray spectroscopy. Results indicated that high RANKL/OPG ratio, TLR4/MyD88 activity, and pro-inflammatory cytokine levels were detected following PD. Impaired biochemical findings paralleled well with severe bone loss and reduced calcium intensity. However, in rats pretreated with melatonin, all above parameters were successfully returned to nearly normal levels with maximal change observed in rats receiving 100 mg/kg. As prophylactic treatment with melatonin effectively normalizes RANKL/OPG signaling by depressing TLR4/MyD88-mediated pro-inflammatory cytokine production, dietary supplement with melatonin may serve as an advanced strategy to strengthen oral health to counteract PD-induced destructive damage.

Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis.

L-3,4-Dihydroxy-6-[F-18]fluorophenylalanine positron emission tomography demonstrating dopaminergic system abnormality in the brains of obsessive-compulsive disorder patients.

AIM: Obsessive-compulsive disorder (OCD) is a chronic disabling neuropsychiatric disorder. Current treatment modalities, such as pharmacological and behavioral methods, are sometimes unsatisfactory. The mesolimbic dopaminergic pathway is supposed to have a role in the pathogenesis of OCD. In this study, L-3,4-Dihydroxy-6-[F-18]fluorophenylalanine (F-18 FDOPA) positron emission tomography (PET) is exploited to investigate the possible abnormality of dopaminergic neuronal circuits in the brains of OCD patients in vivo. METHODS: The study subjects were recruited after psychological assessment and gave written informed consent to participate. The F-18 FDOPA PET scans were performed on five OCD patients and six healthy volunteers at 120 min after 185 MBq of F-18 FDOPA intravenous injection. The PET results were analyzed with the Statistical Parametric Mapping tool. RESULTS: Compared to the healthy subjects, the OCD brains showed increased dopaminergic metabolism in the left frontal premotor cortex (P < 0.001), along with trends toward an increase in the left posterior cingulate gyrus, the left cuneus, the left lingual gyrus, the right cuneus and precuneus, the right lingual gyrus, the right middle temporal gyrus, the left cerebellum, and the right cerebellum (P < 0.01). CONCLUSION: Our observations suggest that the increased dopaminergic neuronal function in these brain areas may be implicated in the pathogenesis of OCD.

Effects of chronic treatment with diosgenin on bone loss in a D-galactose-induced aging rat model.

D-galactose is known to cause oxidative stress and induce aging-related diseases. Our previous study demonstrated that diosgenin can prevent osteoporosis in menopausal rats. The aim of the present study was to determine the effects of oral administration of diosgenin on bone loss in a D-galactose-induced aging rat model. Three groups of twelve-week-old male Wistar rats received a daily injection of D-galactose (150 mg/kg/day, i.p.) and orally administered diosgenin (0, 10, or 50 mg/kg/day) for eight weeks, while a control group received saline injection (1 ml/kg/day, i.p.), then the femurs were taken to measure mechanical and morphological properties. The results showed that frame volume and femur volume decreased and porosity and frame density increased in the D-galactose-induced aging rats compared to controls and that these effects were prevented by co-administration of diosgenin. This suggests that diosgenin might prevent bone loss during aging and provide beneficial effects in osteoporosis in the elderly.

Pneumorrhachis With FDG Uptake Cervical Lesions on PET/CT of a Patient With Suspected Recurrent Hypopharyngeal Cancer.

ABSTRACT: A 57-year-old man presented with odynophagia for 1 week was referred for FDG PET/CT scan to rule out recurrent hypopharyngeal cancer. The FDG PET/CT showed hypermetabolic lesions in hypopharyngeal area and adjacent cervical spine with pneumorrhachis, the presence of intraspinal air, on attenuation CT images, which might indicate a life-threatening infection. An emergency MRI confirmed the presence of cervical spondylodiscitis with an epidural abscess. The patient rapidly progressed to quadriplegia and difficulty voiding on the same day as the PET/CT scan, leading to emergent operation. The patient received antibiotics treatment and discharged 4 months later without evidence of cancer recurrence.

FDG PET/CT Demonstrated Unilateral Striatum Hypometabolism in a Case of Advanced Nasopharyngeal Cancer.

ABSTRACT: A 79-year-old man with nasopharyngeal cancer (NPC) presented with diplopia symptom and a history of diabetes mellitus was referred for an FDG PET/CT scan to determine the pretreatment staging. The FDG PET/CT scan revealed NPC with skull base invasion and decreased FDG uptake at the left striatum. A review of his clinical history and a brain MRI conducted 5 months ago confirmed a previous diagnosis of left hyperglycemic hemichorea. In this NPC patient with inadequate blood sugar control, unilateral striatum hypometabolism may persist for up to 5 months after the initial clinical symptoms.

The effects of perceived stress and life style leading to breast cancer.

Researchers conducted a study in a Taiwanese medical center from June 2009 to June 2011 to investigate the relations of perceived stress and lifestyle to breast cancer. A total of 157 cases and 314 controls completed a structured questionnaire. Using multiple logistic regression models, high perceived stress (adjusted odds ratio [AOR] = 1.65; 95% confidence interval [CI], 1.10-2.47), less than 1,000 kcal of physical activity expenditure per week (AOR, 2.17; 95% CI, 1.39-3.39), and high intake of fried and stir-fried food (AOR, 1.86; 95% CI, 1.24-2.77) were positively associated with breast cancer. Breast cancer was related to joint interactions between high perceived stress and alcohol intake of 11.0 g or more per day (AOR, 2.91; 95% CI, 1.23-6.86), smoking at least one cigarette per day (AOR, 2.52; 95% CI, 1.16-5.47), intake of less than 100 ml of green tea per day (AOR, 2.47; 95% CI, 1.40-4.38), physical activity of less than 1,000 kcal per week (AOR, 3.36; 95% CI, 1.77-6.36), high fried and stir-fried food intake (AOR, 3.18; 95% CI, 1.79-5.63), and high meat and seafood intake (AOR, 1.89; 95% CI, 1.09-3.27). Perceived stress, when combined with potentially risky lifestyle behaviors, may be a contributing factor to breast cancer.

Bladder Distention Demonstrating Vesicourachal Diverticulum on 18 F-FDG PET/CT Images of a Lung Cancer Patient.

ABSTRACT: A 58-year-old man with lung cancer was referred for an 18 F-FDG PET/CT scan for pretreatment staging. The FDG PET/CT scan revealed focal uptakes in the lower abdomen. We differentiated the etiology of the lesions by performing a delayed scan with urine retention and bladder distension. The delayed scan demonstrated a tubular, radioactivity-filled structure arising above the urinary bladder. Combining the FDG PET/CT scan, clinical findings, and ultrasonography, we made the diagnosis of vesicourachal diverticulum.

Long-term outcomes of patients treated with primary stenting for transplant renal artery stenosis: a 10-year case cohort study.

BACKGROUND: The purpose of the present study was to evaluate graft and patient survival and long-term outcomes of primary endoluminal stenting (PES) as an initial treatment for transplant renal artery stenosis (TRAS). METHODS: From December 1999 to March 2010, 744 consecutive patients undergoing renal transplantation were enrolled. Patients were divided into one of two groups: the study group, comprised of 18 patients who underwent PES for TRAS > 60%, and a control group, including the remaining 726 recipients who did not develop TRAS post-transplantation. Primary outcome measures were death-censored graft failure and all-cause mortality. The immediate and long-term effects of PES were evaluated by assessing blood pressure (BP) control and biochemical graft function. RESULTS: The technical success rate for PES was 100%, and minor complication occurred in only one case (5.6% of the study group). With a mean follow-up of 7.1 ± 3.7 and 6.9 ± 2.4 years in the study and control groups, respectively, 4 patients in the study group and 113 patients in the control group reached the primary outcome (log rank P = 0.418). The reduction in stenosis resulted in immediate improvement in BP control and graft function, which persisted throughout the 6 year follow-up period. Restenosis occurred in only one patient (5.6%), but restenosis was not the cause of graft failure. CONCLUSIONS: This study indicated that both the long-term graft and patient survival were as good in TRAS patients treated with PES as in patients without TRAS. The data also supported the use of PES as an initial treatment for TRAS.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.).

In vitro and in vivo osteogenesis of gelatin-modified calcium silicate cement with washout resistance.

The purpose of this study was to evaluate the physicochemical properties and the in vitro and in vivo osteogenesis of the newly developed calcium silicate containing 5 wt% gelatin (CSG) cement compared with calcium silicate (CS) and calcium sulfate hemihydrate (CSH) cements. In addition to the phase composition and microstructure, washout resistance, setting time, and diametral tensile strength of the bone cements were also performed. In vitro examination of cell growth, differentiation, and mineralization were performed with macrophage cell line (RAW 264.7), MG63 human osteoblast-like cells, and human mesenchymal stem cells (hMSCs). The mini-pig model with mandibular alveolar bone defect was used to assess the in vivo function of cement. Histological and histomorphometric assessments were performed at 6 and 12 weeks after implantation. The results indicated that the CS and CSG powders were mainly composed of poorly crystalline ß-dicalcium silicate, and the irregular CSH powders had a highly crystalline phase. After setting, the product of CS and CSG was calcium-silicate-hydrate gel and CSH exhibited a plate-like gypsum crystal structure. The setting time of CS, CSG, and CSH was 19, 35, and 10 min, respectively. Gelatin effectively improved the washout resistance and diametral tensile strength of CS from 2.4 MPa to 3.4 MPa, while CSH had no washout resistance and its strength was 7.6 MPa. The osteogenic activity of MG63 and hMSC cells on the CSG cement surface was consistently shown to be significantly higher than that on the CSH cement surface. Interestingly, CS and CSG cements exhibited lower macrophage expression compared to CSH cements. Twelve week after implantation, the amount of new bone in the defect area of the CS group was slightly higher than that of the CSG and CSH groups. It is concluded that CSG cement had improved anti-washout performance, favorable osteogenesis in vitro and in vivo, which was beneficial for clinical application.

TLD environmental monitoring of new scanner facilities at the Nuclear Medicine Department of the Taiwan Medical University Hospital.

OBJECTIVE: Single-photon emission computed tomography (SPECT) as well as dual energy X-ray absorptiometry (DXA) scanners were designed in July 2018 at the Nuclear Medicine Department (NM), of the Taiwan Medical University Hospital. These scanners emit substantial X-rays from the target, which are tungsten, iron. Therefore, patients undergoing SPECT and DXA diagnosis, in addition to medical personnel, are exposed to undesirable photon leakage. METHODS: Following administration of radiopharmaceuticals, patients become radioactive sources; thus, it is necessary to evaluate a possible increase in the environmental gamma exposure rates in the NM as a result of the operation of the new scanners. A three month evaluation of environmental radiation in the NM was performed using the accurate and sensitive TLD-100H approach, which gives an error rate less than 10%. RESULTS: Detected exposure radiation rates in the NM ranged from 0.12 ± 0.02 to 1.00 ± 0.15 mSv per month, indicating that the imaging room had significantly different radiation rates. The results were compared with previous results, and no significant contribution to the enhancement of environmental gamma radiation was detected, which remained far below the occupational dose recommended by ICRP 60. The minimum detectable dose (MDD) for environmental radiation is also discussed herein to demonstrate the reliability of TLD-100H. CONCLUSION: Recommendations were sent to the authorities of AEC-ROC to implement actions that could reduce doses at these high-dose locations to meet the ALARA principle.

Multicenter integrated positron emission tomography/computer tomography imaging quality assurance accreditation interobserver reliability study with the American College of Radiology phantom.

BACKGROUND: Integrated positron emission tomography/computer tomography (PET/CT) image quality assurance ensures accurate, reproducible, and quantitative assessment of comparable scanner performance. We performed a preliminary multicenter PET/CT imaging quality assurance test with a fillable tomographic phantom in six medical centers in Taiwan. METHODS: The phantom was filled with fixed proportions of fluorine-18 radionuclide solution in the background and with different spheres to simulate cold and hot lesions, and body background radioactivity. Imaging acquisitions were performed by using recommended parameters in different sites according to different brand names of the instrument. All imaging was subjectively scored by eight experienced nuclear medicine physicians as the spatial resolution of four hot vials (score 0-4), six cold spheres (score 0-6), and six cold rod areas (score 0-6), and overall satisfaction (score 0-5). Interobserver correlation and receiver operating characteristic (ROC) curve were analyzed. RESULTS: The detection ability of hot vials, cold spheres, and cold rods was 4.0 ± 0.1, 5.2 ± 0.8, and 3.8 ± 0.9, respectively. Overall satisfaction was 4.0 ± 0.8. The ROC analysis revealed that the area under the curve for hot vials, cold spheres, and cold rods was 0.984, 0.887, and 0.928 respectively. The interobserver correlation for detectability of cold spheres and cold rods was 0.88 and 0.96, respectively. CONCLUSION: The results of the study indicated that (1) PET/CT imaging quality assurance for comparable scanner performance could be established on the basis of a standard phantom and (2) good interobserver correlation can be observed for those with accurate and interpretable results.

[18F]FBAU 3',5'-dibenzoate, a lipophilic prodrug, enhances brain uptake of the cell proliferation tracer [18F]FBAU.

INTRODUCTION: 1-(2-deoxy-2-[(18)F]fluoro-beta-D-arabinofuranosyl)-5-bromouracil ([(18)F]FBAU) is a cell proliferation tracer. However, it does not pass readily through the blood-brain barrier. We synthesized a lipophilic prodrug of [(18)F]FBAU that was intended to enhance brain uptake of [(18)F]FBAU to improve the imaging of brain cell proliferation. METHODS: [(18)F]FBAU was synthesized according to the methods described by Alauddin [J Med Chem 39 (1996) 2835-2843]. The prodrug, 1-(2-deoxy-3,5-O-dibenzoyl-2-[(18)F]fluoro-beta-D-arabinofuranosyl)-5-bromouracil ([(18)F]FBAU 3',5'-dibenzoate), was purified from an intermediate of [(18)F]FBAU. Their lipophilicity was determined by performing octanol/water partition coefficient (log P) measurements. In vitro metabolic fates of the prodrug were examined in rat and mouse plasma and brain homogenates. Brain uptake was determined following iv injection of the radiotracers by killing animals at various time points and dissecting and counting the radioactivity accumulation in the various tissues. RESULTS: Values of log P for [(18)F]FBAU 3',5'-dibenzoate and [(18)F]FBAU were 3.95 and -0.35, respectively. In rat plasma, the prodrug was gradually hydrolyzed to [(18)F]FBAU. Thirty minutes after mixing [(18)F]FBAU 3',5'-dibenzoate in the plasma, 25% of the prodrug had been hydrolyzed. The hydrolysis went more slowly in brain homogenates. At 15 min post injection, relative to animals injected with [(18)F]FBAU, brain uptake of radioactivity in animals injected with [(18)F]FBAU 3',5'-dibenzoate was increased by 150% (P=.005) and 78% (P=.037) in rats and mice, respectively. At 60 min post injection, the radioactive contents extracted from the brain were mostly [(18)F]FBAU. CONCLUSION: The synthesized novel prodrug [(18)F]FBAU 3',5'-dibenzoate has enhanced brain uptake in rodents, suggesting it may be useful as an imaging agent for tracing brain cell proliferation.

Diffuse FDG uptake in acute prostatitis.

Whole body bone scan and abdominal computed tomography (CT) of a 77-year-old man with intractable back pain revealed a destructive bone lesion in the lumbar spine. The F-18 FDG PET/CT scan, performed under the impression of an unknown primary cancer, showed diffusely intense FDG uptake in the enlarged prostate and mild FDG uptake in the lumbar spine. The patient had pyuria and mild fever during admission. Laboratory findings showed elevation of the serum prostate specific antigen (95.69 ng/ml). Blood culture yielded Klebsiella pneumoniae. The prostate biopsy showed acute inflammation with no malignancy and the lumbar spine biopsy showed chronic osteomyelitis.

The Incidence of Totally Implantable Venous Access Devices Insertion and the Associated Abnormalities in Patients With Cancer Revealed in 18F-FDG PET-CT Imaging.

RATIONALE AND OBJECTIVES: The purpose of this retrospective study was to evaluate the incidence of totally implantable venous access devices, also called ports, implantation and the associated abnormalities in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) images for patients with cancer, and to determine the percentage of abnormalities identified in the original reports. MATERIALS AND METHODS: The study aimed to perform a retrospective review of all FDG PET-CT imaging in a 3-year period. Cases of port-associated abnormalities found on the FDG PET-CT images were identified and then correlated with X-ray reports and clinical treatment or follow-up. RESULTS: In total, 2442 FDG PET-CT scans were retrospectively reviewed. Among them, 897 (897 of 2442, 36.7%) demonstrated port implantation. Abnormalities, including 22 port fractures (22 of 897, 2.45%), 14 malposition (1.56%), one infection (0.11%), and one embraced by a fibrin sheath or tumor (0.11%) were found. Only the infectious one had clinical symptoms. Among the 22 fractured ports, eight fractured catheters migrated and became dislodged. All of the malpositioned ports, except two in the contralateral subclavian vein, were found in the ipsilateral jugular vein. Both the port infection and the port embraced by a fibrin sheath or tumor occurred at the tips of the devices, which demonstrated FDG uptake in the mediastinal region. Only seven of the 38 (18.42%) images of port abnormalities had been identified in the original reports. CONCLUSIONS: Based on this study, we recommend that the interpretation of FDG PET-CT scans should include a checklist to record all metallic device implantations and to interpret the whole-body X-ray topography as a standard part of PET-CT image report.

The Relationship of Vocabulary Learning Strategies and Self-Efficacy with Medical English and Terminology.

This study examined the relationship between the use of vocabulary learning strategies and self-efficacy in medical English learning, and whether after an initial six-week course to master the basics of medical terminology, those with higher use of vocabulary learning strategies and those with a higher degree of self-efficacy would have significant score improvements in the medical English proficiency. Second-year medical students (N = 115; M age = 19.6, SD = 0.5; 82 men, 33 women) participated in the study. A one-group pretest-posttest design was used. Measures included medical English tests, the English Vocabulary Learning Strategies Survey (EVLSS), and the English Learning Self-Efficacy Scale (ELSES). Results showed that there was no significant correlation between vocabulary learning strategies and English learning self-efficacy. In addition, as a whole, vocabulary learning strategies and self-efficacy significantly predicted students' score improvements in medical English proficiency.

Prostate Lymphoma Complicated With Prostatorectal Fistula and Multifocal Infection After Chemotherapy.

A 67-year-old man with a biopsy proving prostate diffuse large B-cell lymphoma was referred for an F-FDG PET/CT scan for postchemotherapy treatment monitoring. The FDG PET/CT scan revealed a significant reduction of prostate lymphoma and a prostatorectal fistula formation. The patient developed Klebsiella pneumoniae sepsis, and a follow-up FDG PET/CT 3 months later revealed multifocal lung, bone, and muscle infection. The FDG PET/CT scans of this patient not only demonstrated the effectiveness of chemotherapy for prostate lymphoma but also the complications of a prostatorectal fistula and multiple infectious foci.

SPECT findings in the Kleine-Levin syndrome.

STUDY OBJECTIVES: The Kleine-Levin Syndrome, is a rare disorder with onset during teenage years, but little is known on etiopathogenesis. Seven subjects with Kleine-Levin Syndrome accumulated over time had systematic SPECT studies during (n=5) and out (n=7) of the symptomatic period. SUBJECTS: Seven boys with symptom onset between 11 and 17 years of age and at least 2 episodes per year were followed for a mean of 6 years. METHODS: Electroencephalogram awake-asleep, computed tomography scan, and magnetic resonance imaging studies were performed before Tc-99m ECD single photon emission tomography (SPECT) obtained during day 4 or 5 (n=5) and at least 1 month away from the symptomatic period (n=7). RESULTS: All imaging tests except SPECT were normal. Hypoperfusion of both thalami were seen during the symptomatic period that completely disappeared during the asymptomatic period. Hypoperfusion in other regions were also noted in some, but not all subjects. They persisted during the asymptomatic period in 2 cases over the temporal lobe (2/7 cases), frontal lobe (1/7 cases), and basal ganglia (1/7 cases). The largest amount of persistent hypoperfusion was seen in the subject with longest clinical evolution. CONCLUSION: Hypoperfusion of the thalamus is a consistent finding during the symptomatic period, but perfusion abnormalities may persist even during the asymptomatic period. The longer the duration of the syndrome, the more extended the hypoperfusion regions during the asymptomatic period.

Coincidence planar imaging for dynamic [18F]FDG uptake in nude mice with tumors and inflammation: correlated with histopathology and micro-autoradiography.

The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.