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1.  [18F]FLT-PET to predict pharmacodynamic and clinical response to cetuximab therapy in Ménétrier’s disease 
Annals of nuclear medicine  2012;26(9):757-763.
Molecular imaging biomarkers of proliferation hold great promise for quantifying response to personalized medicine. One such approach utilizes the positron emission tomography (PET) tracer 3′-deoxy-3′ [18F]-fluorothymidine ([18F]FLT), an investigational agent whose uptake reflects thymidine salvage-dependent DNA synthesis. The goal of this study was to evaluate [18F]FLT-PET in the setting of Ménétrier’s disease (MD), a rare, premalignant hyperproliferative disorder of the stomach treatable with cetuximab therapy. Over 15 months, a patient with confirmed MD underwent cetuximab therapy and was followed with sequential [18F]FLT-PET. For comparison to MD, an [18F]FLT-PET study was conducted in another patient to quantify uptake in a normal stomach.Prior to cetuximab therapy, stomach tissue in MD was easily visualized with [18F]FLT-PET, with pre-treatment uptake levels exceeding normal stomach uptake by approximately 4-fold. Diminished [18F]FLT-PET in MD was observed following the initial and subsequent doses of cetuximab and correlated with clinical resolution of the disease. To our knowledge, this study reports the first clinical use of [18F]FLT-PET to assess proliferation in a premalignant disorder. We illustrate that the extent of MD involvement throughout the stomach could be easily visualized using [18F]FLT-PET, and that response to cetuximab could be followed quantitatively and non-invasively in sequential [18F]FLT-PET studies. Thus, [18F]FLT-PET appears to have potential to monitor response to treatment in this and potentially other hyperproliferative disorders.
doi:10.1007/s12149-012-0636-x
PMCID: PMC3543701  PMID: 22821337
FLT; proliferation; treatment response; EGFR; Ménétrier’s disease
2.  Dual-time-point F-18 FDG PET/CT imaging for differentiating the lymph nodes between malignant lymphoma and benign lesions 
Annals of Nuclear Medicine  2012;27(2):163-169.
Purpose
The purpose of the present study is to evaluate the clinical value of dual-time-point F-18 FDG PET/CT imaging to differentiate malignant lymphoma (ML) from benign lymph node (BLN).
Materials and methods
The subjects were 310 lymph nodes in 84 patients (195 ML lesions in 30 patients and 115 BLN in 54 patients associated with various etiologies.). F-18 FDG PET/CT scan was performed at 50 min (early scan) and at 100 min (delayed scan) after the injection. First, the maximum standardized uptake value (SUVmax) of each lesion at early and delayed scans was calculated. Second, we estimated the difference between early and delayed SUVmax (D-SUVmax) and the retention index (RI-SUVmax) to evaluate the change of tracers in the lesions. Furthermore, proper cut-off values of them were evaluated using receiver operating characteristic analysis. The efficacy of each parameter was analyzed with ANOVA.
Results
Delayed SUVmax and D-SUVmax in ML were significantly higher than those in BLN. Proper cut-off value in delayed SUVmax was 4.0 and in D-SUVmax was 1.0. When the proper cut-off value in D-SUVmax was applied, the D-SUVmax yielded the role of diagnosis with sensitivity of 82.6 %, specificity of 65.2 %, positive predictive value of 80.1 % and negative predictive value of 68.8 %, respectively.
Conclusions
The delayed SUVmax and D-SUVmax were useful indices to differentiate ML from BLN, regardless of histologic subtype. Dual-time-point F-18 FDG PET/CT imaging may help to consider whether there is any need to proceed to more invasive tests, such as biopsy, in individual patients.
doi:10.1007/s12149-012-0669-1
PMCID: PMC3575551  PMID: 23188388
18F-FDG PET/CT; Dual-time-point imaging; Lymphoma; Benign lymph node; Standardized uptake value
3.  Three-dimensional brain phantom containing bone and grey matter structures with a realistic head contour 
Annals of Nuclear Medicine  2012;27(1):25-36.
Introduction
A physical 3-dimensional phantom that simulates PET/SPECT images of static regional cerebral blood flow in grey matter with a realistic head contour has been developed. This study examined the feasibility of using this phantom for evaluating PET/SPECT images.
Methods
The phantom was constructed using a transparent, hydrophobic photo-curable polymer with a laser-modelling technique. The phantom was designed to contain the grey matter, the skull, and the trachea spaces filled with a radioactive solution, a bone-equivalent solution of K2HPO4, and air, respectively. The grey matter and bone compartments were designed to establish the connectivity. A series of experiments was performed to confirm the accuracy and reproducibility of the phantom using X-ray CT, SPECT, and PET.
Results
The total weight was 1997 ± 2 g excluding the inner liquid, and volumes were 563 ± 1 and 306 ± 2 mL, corresponding to the grey matter and bone compartments, respectively. The apparent attenuation coefficient averaged over the whole brain was 0.168 ± 0.006 cm−1 for Tc-99 m, which was consistent with the previously reported value for humans (0.168 ± 0.010 cm−1). Air bubbles were well removed from both grey-matter and bone compartments, as confirmed by X-ray CT. The phantom was well adapted to experiments using PET and SPECT devices.
Conclusion
The 3-dimensional brain phantom constructed in this study may be of use for evaluating the adequacy of SPECT/PET reconstruction software programs.
doi:10.1007/s12149-012-0655-7
PMCID: PMC3549246  PMID: 23011903
Brain phantom quality control; SPECT; PET; Attenuation correction
4.  Performance of a semiconductor SPECT system: comparison with a conventional Anger-type SPECT instrument 
Annals of Nuclear Medicine  2012;27(1):11-16.
Objective
The performance of a new single photon emission computed tomography (SPECT) scanner with a cadmium-zinc-telluride (CZT) solid-state semiconductor detector (Discovery NM 530c; D530c) was evaluated and compared to a conventional Anger-type SPECT with a dual-detector camera (Infinia).
Methods
Three different phantom studies were performed. Full width at half maximum (FWHM) was measured using line sources placed at different locations in a cylindrical phantom. Uniformity was measured using cylindrical phantoms with 3 different diameters (80, 120, and 160 mm). Spatial resolution was evaluated using hot-rod phantoms of various diameters (5, 9, 13, 16, and 20 mm). Three different myocardial phantom studies were also performed, acquiring projection data with and without defects, and evaluating the interference of liver and gallbladder radioactivity. In a clinical study, the D530c employed list-mode raw data acquisition with electrocardiogram (ECG)-gated acquisition over a 10-min period. From the 10-min projection data, 1-, 3-, 5-, 7- and 10-min SPECT images were reconstructed.
Results
The FWHM of the D503c was 1.73–3.48 mm (without water) and 3.88–6.64 mm (with water), whereas the FWHM of the Infinia was 8.17–12.63 mm (without water) and 15.48–16.28 mm (with water). Non-uniformity was larger for the D530c than for the Infinia. Truncation artifacts were also observed with the D530c in a Φ160 mm phantom. The contrast ratio, as defined by myocardial defect/non-defect ratio, was better for the D530c than for the Infinia, and the influence from liver and gallbladder radioactivities was less. Quantitative gated SPECT (QGS) software demonstrated significant differences between data captured over a 10-min period, relative to those acquired over periods of <5 min; there was no difference between ejection fractions calculated using data capture for periods ≥5 min (p < 0.05).
Conclusions
The D530c is superior to the Infinia, with regard to both spatial resolution and sensitivity. In this study, these advantages were confirmed by the myocardial phantom and in a clinical setting, using the QGS software.
doi:10.1007/s12149-012-0653-9
PMCID: PMC3549244  PMID: 22956363
Semiconductor camera; Spatial resolution; Sensitivity; Myocardial SPECT
5.  Time course of bone metabolism at the residual ridge beneath dentures observed using 18F-fluoride positron emission computerized-tomography/computed tomography (PET/CT) 
Annals of Nuclear Medicine  2012;26(10):817-822.
Objective
Excessive pressure due to wearing mal-adapting dentures is well known to cause residual bone resorption beneath the denture. X-rays have been commonly utilized to evaluate the changes in the bone beneath the denture. However, X-ray images merely detect bone density and relatively large changes in the bone shape and structure, whereas nuclear medicine imaging can detect functional changes, which occur prior to structural changes. This article aimed to describe the time course of the bone metabolism at the residual ridge beneath the denture following denture use by 18F-fluoride positron emission computerized-tomography (PET)/computed tomography (CT) scanning.
Methods
Three subjects, who had a free-end edentulous mandible, were treated with a denture replacing the edentulous region of the dental arch. The metabolic changes in the residual bone beneath the denture were assessed by 18F-fluoride PET/CT imaging. 18F-fluoride PET/CT scanning was performed at baseline, and 4–6 and 13 weeks after denture use. A volume of interest (VOI) was placed on their mandibles at the edentulous region beneath the denture on the PET/CT image. CT value and mean standardized uptake value (SUV) of the VOI were calculated. The difference in the time variation between the CT value and SUV was analyzed.
Results
The adaptation of the denture base to the residual ridge was successful, and there was no trouble such as pain at the residual ridge beneath the denture. The SUVs of each VOI significantly increased at 4–6 weeks after denture use and then decreased at 13 weeks in all three subjects (P < 0.05; two-way ANOVA, Dunnett test). On the other hand, the CT images showed no obvious changes in the bone shape or structure beneath the dentures, and the CT values of each VOI remained static after denture use in all three subjects.
Conclusions
This study indicates that in the present first-time removable partial denture (RPD) users, wearing of a well-adapted RPD initially increased bone metabolism beneath the denture and then decreased it at around 13 weeks after RPD use without any bone structural changes detectable by clinical X-rays. These metabolic changes are a mechanobiological reaction to the pressure induced by RPD use.
doi:10.1007/s12149-012-0648-6
PMCID: PMC3524501  PMID: 22903818
Bone metabolism; Denture; Mechanobiology; 18F-fluoride PET
6.  F-18 fluorodeoxyglucose uptake and water-perfusable tissue fraction in assessment of myocardial viability 
Annals of Nuclear Medicine  2012;26(8):644-655.
Objectives
15O-water-perfusable tissue fraction (PTF) has been shown to be a potential index for assessing myocardial viability in PET, an alternative to 18F-fluorodeoxyglucose (FDG). This study aimed to directly compare these two independent methods in assessing myocardial viability in patients with abnormal wall motion.
Methods
PET study was performed on 16 patients with previous myocardial infarction, before coronary artery bypass graft operation (CABG). The protocol included a 15O-carbonmonoxide static, a 15O-water dynamic and an 18F-FDG dynamic scan, during the euglycemic hyperinsulinemic clamp. Echocardiography was performed at the time of PET and 5–12 months after the CABG, and the wall motion recovery was evaluated on segmental and global bases. Consistency between PTF and 18F-FDG was evaluated visually and also in a quantitative manner. Predictive values for the wall motion recovery were also compared between the two approaches.
Results
The image quality of 18F-FDG was superior to that of 15O-water. The qualitative PTF showed significantly smaller defects than 18F-FDG, and the quantitative PTF showed slightly greater values than 18F-FDG in the infarcted region. The two methods were, however, consistent visually and also quantitatively. The predictive values of the wall motion recovery were almost equal between the two approaches. The absolute 18F-FDG uptake was varied in normal segments, and predictive values for the wall motion recovery by the absolute 18F-FDG was less (accuracy: 80 %) compared with those by the relative 18F-FDG (accuracy: 87 %) and the quantitative PTF (accuracy: 89 %).
Conclusion
Despite the small sample size, PTF appears to give consistent results with the 18F-FDG approach, and might be an alternative viability assessment.
doi:10.1007/s12149-012-0631-2
PMCID: PMC3475968  PMID: 22797841
Myocardial viability; Chronic myocardial infarction; 18F-FDG; Water perfusable tissue fraction; Positron emission tomography
7.  Computer-aided diagnosis system for bone scintigrams from Japanese patients: importance of training database 
Annals of Nuclear Medicine  2012;26(8):622-626.
Aim
Computer-aided diagnosis (CAD) software for bone scintigrams have recently been introduced as a clinical quality assurance tool. The purpose of this study was to compare the diagnostic accuracy of two CAD systems, one based on a European and one on a Japanese training database, in a group of bone scans from Japanese patients.
Method
The two CAD software are trained to interpret bone scans using training databases consisting of bone scans with the desired interpretation, metastatic disease or not. One software was trained using 795 bone scans from European patients and the other with 904 bone scans from Japanese patients. The two CAD softwares were evaluated using the same group of 257 Japanese patients, who underwent bone scintigraphy because of suspected metastases of malignant tumors in 2009. The final diagnostic results made by clinicians were used as gold standard.
Results
The Japanese CAD software showed a higher specificity and accuracy compared to the European CAD software [81 vs. 57 % (p < 0.05) and 82 vs. 61 % (p < 0.05), respectively]. The sensitivity was 90 % for the Japanese CAD software and 83 % for the European CAD software (n.s).
Conclusion
The CAD software trained with a Japanese database showed significantly higher performance than the corresponding CAD software trained with a European database for the analysis of bone scans from Japanese patients. These results could at least partly be caused by the physical differences between Japanese and European patients resulting in less influence of attenuation in Japanese patients and possible different judgement of count intensities of hot spots.
doi:10.1007/s12149-012-0620-5
PMCID: PMC3475966  PMID: 22729550
Computer-aided diagnosis; Bone scintigram; Bone metastases; Artificial neural networks
8.  Detection of recurrent prostate cancer with 18F-fluorocholine PET/CT in relation to PSA level at the time of imaging 
Annals of Nuclear Medicine  2012;26(6):501-507.
Purpose
To evaluate fluorine-18 fluorocholine (FCH) PET/CT for the detection of recurrent prostate cancer in relation to prostate-specific antigen (PSA) level.
Methods
FCH PET/CT was performed in 50 patients with rising PSA levels at follow-up of primary treatment of prostate cancer (radical prostatectomy in 28, radiation therapy in 13, and brachytherapy in 9). PET detection rates were determined at various PSA thresholds and examined by receiver operating characteristic analysis.
Results
Findings consistent with recurrent prostate cancer were noted on FCH PET/CT in 31/50 (62 %) patients, with positive findings in 17/18 (94 %), and 11/13 (85 %), 2/7 (29 %), and 1/12 (8 %) patients with PSA >4, >2–4, >0.5–2, and ≤0.5 ng/mL, respectively. These findings were indicative of local/regional recurrence in 23 cases and systemic recurrence in 8 cases, with only a single route of recurrence (i.e., either hematogenous, lymphatic, or intraprostatic) in 84 % of PET scans with positive findings. Abnormal tumor activity was detected in 88 % of patients with a PSA level of 1.1 ng/mL or higher, and in only 6 % of patients with a PSA level below this threshold value.
Conclusion
FCH PET/CT may serve to identify the route of tumor progression in patients with recurrent prostate cancer; however, the likelihood of tumor detection may be related to the PSA level at the time of imaging.
doi:10.1007/s12149-012-0601-8
PMCID: PMC3400027  PMID: 22549847
Fluorocholine; Prostate cancer; Positron emission tomography
9.  Normal values for nuclear cardiology: Japanese databases for myocardial perfusion, fatty acid and sympathetic imaging and left ventricular function 
Annals of Nuclear Medicine  2010;24(3):125-135.
Myocardial normal databases for stress myocardial perfusion study have been created by the Japanese Society of Nuclear Medicine Working Group. The databases comprised gender-, camera rotation range- and radiopharmaceutical-specific data-sets from multiple institutions, and normal database files were created for installation in common nuclear cardiology software. Based on the electrocardiography-gated single-photon emission computed tomography (SPECT), left ventricular function, including ventricular volumes, systolic and diastolic functions and systolic wall thickening were also analyzed. Normal databases for fatty acid imaging using 123I-beta-methyl-iodophenyl-pentadecanoic acid and sympathetic imaging using 123I-meta-iodobenzylguanidine were also examined. This review provides lists and overviews of normal values for myocardial SPECT and ventricular function in a Japanese population. The population-specific approach is a key factor for proper diagnostic and prognostic evaluation.
doi:10.1007/s12149-009-0337-2
PMCID: PMC2855806  PMID: 20108130
Normal database; Myocardial perfusion imaging; Systolic and diastolic function; 123I-BMIPP database; 123I-MIBG database
10.  [F-18]-fluorodeoxyglucose PET–CT of the normal prostate gland 
Annals of nuclear medicine  2008;22(9):787-793.
Objective
We determined the glucose metabolism and computed tomographic (CT) density of the normal prostate gland in relation to age and prostate size on [F-18] fluorodeoxyglucose positron emission tomography (PET)–CT.
Methods
We determined the CT density (Hounsfield Units, HU) and glucose metabolism (standardized uptake value, SUV) of the normal prostate in 145 men (age range 22–97 years) on PET–CT scans which were performed for indications unrelated to prostate pathology. Correlations among SUV, HU, prostate size, and age were calculated using Pearson’s correlation coefficients, scatter plots, and linear regression trend lines. The SUV and HU values were also compared among different primary cancer types using the Kruskal–Wallis test.
Results
The population average and range of the normal prostate size were 4.3 ± 0.5 cm (mean ± SD) and 2.9– 5.5 cm, respectively. The population average of mean and maximum CT densities was 36.0 ± 5.1 HU (range 23–57) and 91.7 ± 20.1 HU (range 62–211), respectively. The population average of mean and maximum SUV was 1.3 ± 0.4 (range 0.1–2.7) and 1.6 ± 0.4 (range 1.1– 3.7), respectively. Mean SUV tended to decrease as the prostate size increased (r = −0.16, P = 0.058). Higher mean HU was correlated with higher mean SUV (r = 0.18, P = 0.033). The strongest association was observed between age and prostate size. The prostate gets larger as age increases (r = 0.32, P < 0.001). Prostate mean SUV, max SUV, mean HU, and max HU were not significantly different among different types of primary cancers.
Conclusions
Although the normal prostate size increases with age, it does not significantly affect the gland’s metabolism and CT density, and therefore age–correction of these parameters may be unnecessary.
doi:10.1007/s12149-008-0177-5
PMCID: PMC2636719  PMID: 19039557
Prostate; FDG; PET–CT

Results 1-10 (10)