Annals of Nuclear Medicine (v.29, #9)

Predicting pleural invasion using HRCT and 18F-FDG PET/CT in lung adenocarcinoma with pleural contact by Takashi Tanaka; Takayoshi Shinya; Shuhei Sato; Toshiharu Mitsuhashi; Koichi Ichimura; Junichi Soh; Shinichi Toyooka; Mitsumasa Kaji; Shinichiro Miyoshi; Susumu Kanazawa (757-765).
To evaluate the relevance of high-resolution computed tomography (HRCT) findings and fluorine-18-fluorodeoxyglucose (18F-FDG) uptake for risk stratification of visceral pleural invasion by lung adenocarcinoma.The HRCT findings and 18F-FDG uptake for lung adenocarcinomas with pleural contact on CT were retrospectively analyzed in 208 consecutive patients (94 females and 114 males; median age, 69.0 years) between January 2009 and December 2013, with institutional review board approval. The HRCT findings and maximum standardized uptake value (SUVmax) were recorded for each patient. Multivariate logistic regression was used for statistical analysis, and subgroup analysis stratified for whole tumor size ≤3 cm was also performed.Multivariate analysis showed that SUVmax [odds ratio (OR) 1.09, 95 % confidence interval (CI) 1.02–1.16, P = 0.014] and obtuse angle (OR 4.14, 95 % CI 1.97–8.74, P < 0.001) were significant independent predictors for visceral pleural invasion. Receiver operating characteristic (ROC) analysis showed that, compared with the multivariate models [area under the curve (Az) 0.819–0.829], SUVmax alone (Az 0.815) was useful in predicting visceral pleural invasion. In the subgroup analysis, multivariate analysis showed that SUVmax (OR 1.29, 95 % CI 1.12–1.50, P = 0.001) and contact length with the pleura (OR 1.13, 95 % CI 1.05–1.22, P = 0.001) were significant independent predictors for visceral pleural invasion. ROC analysis showed that SUVmax alone (Az 0.844) showed similar diagnostic performance to the multivariate models (Az 0.845–0.857).SUVmax alone and multivariate models including SUVmax are useful for the prediction of visceral pleural invasion by lung adenocarcinoma.
Keywords: Lung adenocarcinoma; Visceral pleural invasion; 18F-FDG; PET/CT; HRCT

FDG uptake observed around the lumbar spinous process: relevance to Baastrup disease by Kayo Nishimatsu; Yuji Nakamoto; Takayoshi Ishimori; Kaori Togashi (766-771).
In positron emission tomography (PET) with F-18-fluorodeoxyglucose (FDG), non-tumorous focal uptake is often observed around the lumbar spinous processes (LSPs). Close approximation of LSPs with sclerosis is often seen, which is called Baastrup disease. The aim of this study was to characterize this finding in terms of location and subjects’ age and investigate the relation between PET and CT findings.The PET/CT scans of 40 patients each in the fifth, sixth, seventh, eighth, and ninth decades were screened for FDG uptake around the LSPs from L1–2 through L5–S1. Patients with metastasis to the lumbar spine or recent chemotherapy or rheumatoid arthritis-related disease were excluded. Focal uptake greater than blood pool activity was considered positive. Positive uptake was compared among the ages and locations. We also evaluated the relationship between FDG uptake and CT morphology.Overall, focal uptake was observed in 122 LSPs in 71 patients. At least one positive uptake was seen in 9, 21, 15, 12, and 14 of 40 patients (16, 30, 30, 20, and 26 of 200 regions) in each age group of 40s through 80s, respectively (p = 0.12). As for the location, uptake around L1–2, L2–3, L3–4, L4–5, and L5–S1 was observed in 19, 22, 39, 35, and 7 regions, respectively (p < 0.01). There was no statistically significant difference in PET positivity among the five age groups, but positive uptake was predominantly seen in L3–4. Degeneration on CT was apparent in 58, 74, 108, 123, and 144 regions in each age group, respectively (p < 0.01), and in 38, 79, 131, 151, and 108 regions in each location, respectively (p < 0.01). The PET positive ratio was higher in CT positive group than in CT negative group (14 vs. 10 %, p < 0.05), but there was no significant difference of quantitative values (p = 0.10). Of 42 regions in 27 patients who had serial PET/CT scans that were initially PET-positive, 35 regions (83 %) turned negative on a later PET-scan.Focal uptake around the LSPs was commonly seen in the mid-lumbar vertebrae, independent of age, and was not always correlated with morphological changes. This uptake should not be assumed to represent osseous metastasis.
Keywords: Positron emission tomography; Computed tomography; Spine; Lumbar spinous process; Baastrup disease

Relationship of quantitative parameters of myocardial perfusion SPECT and ventricular arrhythmia in patients receiving cardiac resynchronization therapy by Po-Nien Hou; Shih-Chuan Tsai; Wan-Yu Lin; Chien-Ming Cheng; Kuo-Feng Chiang; Yu-Cheng Chang; Jin-Long Huang; Guang-Uei Hung; Shih-Ann Chen; Ji Chen (772-778).
Ventricular arrhythmia is the major cause of sudden cardiac death for patients with heart failure, including those receiving implantation of cardiac resynchronization therapy (CRT). The purpose of this study was to assess the value of myocardial perfusion SPECT (MPS) in predicting ventricular arrhythmia for patients with CRT.Fifty-one patients (35 males, mean age 64 ± 12 years) who had received CRT for at least 6 months were enrolled for resting gated MPS. Three main quantitative parameters of MPS, including extent of myocardial scar, left ventricular ejection fraction (LVEF) and LV dyssynchrony (phase SD), were generated by Emory Cardiac Toolbox. Using the recorded ventricular arrhythmia in the device, including ventricular tachycardia (VT) and ventricular fibrillation (VF), as the primary end point, the value of quantitative parameters of MPS in predicting the development of VT/VF was assessed.Twenty (39 %) of the 51 patients developed VT/VF during the follow-up (15.3 ± 12.7 months). The patients with VT/VF had significantly lower LVEF (24 ± 12 vs. 36 ± 17 %, p < 0.005), larger scar areas (36 ± 19 vs. 22 ± 12 %, p < 0.05) and larger phase SD (57° ± 20° vs. 43° ± 17°, p < 0.01). When categorizing the patients by the median values of LVEF, scar and phase SD, univariate regression analysis showed that lower LVEF (<29 %), larger scar (>23 %) and larger phase SD (>50°) were related to the development of VT/VF (p = 0.006, 0.011 and 0.064, respectively). However, only LVEF was marginally significant as an independent predictor of VT//VF on multivariate regression analysis (p = 0.0573). Survival analysis with Kaplan–Meier curves showed that the survival probability for VT/VF in those with LVEF >29 %, scar areas <23 % and phase SD < 50° was significantly better than in the others (HR 5.16, 95 % CI 1.20–22.16) by log-rank test (χ 2 = 5.9894, p = 0.014).Lower LVEF, larger scar and/or more dyssynchrony assessed by MPS were related to the development of ventricular arrhythmia for patients with CRT, and further defibrillator implantation may be considered for these patients.
Keywords: SPECT; Quantitation; Phase analysis; Cardiac resynchronization therapy; Ventricular arrhythmia

Arginine–arginine–leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model.The hexapeptide, glutamic acid–cysteine–glycine (ECG)–RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG–RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g.A high yield of Tc-99m ECG–RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG–RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG–RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG–RRL accumulated minimally in inflammatory lesions.We successfully developed Tc-99m ECG–RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG–RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG–RRL effectively distinguished between cancerous tissue and inflammatory lesions.
Keywords: Arginine–arginine–leucine; RRL; Tc-99m; Tumor imaging

Carbon-14 urea breath test: does it work in patients with partial gastric resection? by Fuat Dede; Hüseyin Civen; Faysal Dane; Mehmet Aliustaoglu; Serdar Turhal; Halil Turgut Turoglu; Sabahat Inanir (786-791).
The diagnostic value of Carbon-14 urea breath test (C-14 UBT) in the detection of Helicobacter pylori (H. pylori) infection in non-operated patients has been proved. However, the efficacy of C-14 UBT in patients with partial gastric resection (PGR) has not been evaluated yet. Herein, the results of the C-14 UBT and H. pylori stool antigen test (HpSAT) in this patient group were compared with the endoscopic findings.Multi-breath samples C-14 UBT and HpSAT were performed in all patients on the same day. Histology was used as a gold standard for testing C-14 UBT and HpSAT diagnostic efficacies.30 patients (mean age: 54.6 ± 11 year) with PGR were included. The sensitivity and specificity of standard C-14 UBT were 29 and 100 %, respectively. When breath samples were collected at 20th min, and >35 CPM was selected as radioactivity threshold, the sensitivity raised to 86 % without any loss of specificity. The specificity and sensitivity of the HpSAT were 71 and 96 %, respectively.The sensitivity of the standard C-14 UBT was very poor for patients with PGR, and results of HpSAT were superior in this population. Certain modifications are needed if C-14 UBT is to be used in PGR patients.
Keywords: Carbon-14 urea breath test; Stool antigen test; Partial gastrectomy; Gastric cancer; Helicobacter pylori

Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults by Yoshinori Yamada; Hiroshi Nakatani; Hisashi Yanaihara; Masahiro Omote (792-798).
Technetium etarfolatide (99mTc-EF) is a radioactive diagnostic imaging agent that was developed to assess the expression of folate receptors in tumors. Administering folic acid prior to the administration of 99mTc-EF has been shown to improve SPECT images. Here, we conducted a phase I clinical trial to assess the safety, pharmacokinetics, and radiation dosimetry of 99mTc-EF injection following pre-administration of folic acid in healthy Japanese male adults.Six healthy Japanese male adults were enrolled in the study. Folic acid was intravenously administered, followed 1–3 min later by an intravenous injection of 99mTc-EF (740 MBq ± 20 %). Assessments of subjective symptoms and objective findings, electrocardiograms, physical examination, and laboratory tests were performed before and up to 7 days after the injection to assess the safety of 99mTc-EF. Blood and urine collections and whole-body planar imaging were conducted at various time points up to 24 h after the injection to assess the pharmacokinetics of 99mTc-EF. The internal radiation dosimetry was calculated based on the pharmacokinetics results using the MIRD method.Five adverse events were observed in three subjects (50 %) after administration of the folic acid and 99mTc-EF, while these events were mild and non-serious. Of those five events, three were considered to be related to the administered agents. The radioactivity in blood rapidly decreased and showed a biphasic profile. The activity of 99mTc-EF at 5 min post injection was largest in the bone marrow, followed by the liver and kidneys, and had decreased within 24 h in all organs/tissues without appreciable retention. The pharmacokinetics results suggested that 99mTc-EF was mainly eliminated by kidney. The results also suggested that when administered at 925 MBq of 99mTc-EF, which is the maximum dose generally used for clinical trials in other countries, the corresponding effective dose of 99mTc-EF is equal to or less than those determined for the current radioactive diagnostic imaging agents.The results of this study assessing the safety and radiation dosimetry of 99mTc-EF with folic acid pre-administration suggested that folic acid and 99mTc-EF should be appropriate for further studies. No pharmacokinetics concerns were noted.
Keywords: 99mTc-etarfolatide; Folate receptor; Companion diagnostics; SPECT; Phase I

Evaluation of a short dynamic 18F-fluoride PET/CT scanning method to assess bone metabolic activity in spinal orthopedics by Marloes J. M. Peters; Roel Wierts; Elisabeth M. C. Jutten; Servé G. E. A. Halders; Paul C. P. H. Willems; Boudewijn Brans (799-809).
A complication after spinal fusion surgery is pseudarthrosis, but its radiological diagnosis is of limited value. 18F-fluoride PET with its ability to assess bone metabolism activity could be of value. The goal of this study was to assess the clinical feasibility of calculating the static standardized uptake value (SUV) from a short dynamic scan without the use of blood sampling, thereby obtaining all dynamic and static parameters in a scan of only 30 min. This approach was tested on a retrospective patient population with persisting pain after spinal fusion surgery.In 16 patients, SUVs (SUVmax, SUVmean) and kinetic parameters (K 1, k 2, k 3, v b, K i,NLR, K 1/k 2, k 3/(k 2 + k 3), K i,patlak) were derived from static and dynamic PET/CT scans of operated and control regions of the spine, after intravenous administration of 156–214 MBq 18F-fluoride. Parameter differences between control and operated regions, as well as between pseudarthrosis and fused segments were evaluated. SUVmean at 30 and 60 min was calculated from kinetic parameters obtained from the dynamic data set (SUVmean,2TCM). Agreement between measured and calculated SUVs was evaluated through Bland–Altman plots.Overall, statistically significant differences between control and operated regions were observed for SUVmax, SUVmean, K i,NLR, K i,patlak, K 1/k 2 and k 3/(k 2 + k 3). Diagnostic CT showed pseudarthrosis in 6/16 patients, while in 10/16 patients, segments were fused. Of all parameters, only those regarding the incorporation of bone [K i,NLR, K i,patlak, k 3/(k 2 + k 3)] differed statistically significant in the intervertebral disc space between the pseudarthrosis and fused patients group. The mean values of the patient-specific blood clearance rate $$ au^{*}$$ τ ∗ differed statistically significant between the pseudarthrosis and the fusion group, with a p value of 0.011. This may correspond with the lack of statistical significance of the SUV values between pseudarthrosis and fused patients. Bland–Altman plots show that calculated SUVmean,2TCM values corresponded well with the measured SUVmean values.This study shows the feasibility of a 30-min dynamic 18F-fluoride PET/CT scanning and this may provide dynamic parameters clinically relevant to the diagnosis of pseudarthrosis.
Keywords: 18F-fluoride PET/CT; SUV; Kinetic modeling; Lumbar spine; Spinal fusion

Biodistribution and estimation of radiation-absorbed doses in humans for 13N-ammonia PET by Chang Yi; Donglan Yu; Xinchong Shi; Qiao He; Xuezhen Zhang; Xiangsong Zhang (810-815).
To evaluate the biodistribution of radiation-absorbed doses of 13N-ammonia in healthy people.Five healthy human subjects underwent whole-body PET and CT scans after injection of 555–740 MBq of 13N-ammonia. Five serial dynamic emission scans in each healthy volunteer were acquired. Regions of interest were drawn on the CT image and transferred to the corresponding transverse PET slice. Estimates of the radiation-absorbed doses were calculated using the medical internal radiation dosimetry method.The highest concentrations of 13N-ammonia were found in the heart and liver, followed by pancreas, brain, spleen and stomach. The highest absorbed organ doses were to the heart wall (7.14E−03 ± 3.63E−03 mGy/MBq) and kidneys (6.02E−03 ± 3.53E−03 mGy/MBq). The effective dose (ED) was 6.58E−03 ± 1.23E−03 mSv/MBq.With these new estimates for 13N-ammonia dosimetry, the results for Chinese people were not appreciably different from those of the previous study performed with old devices. As one of the most important myocardial perfusion PET tracers, the whole-body 13N-ammonia PET appears to be safe for humans, yielding a relatively modest radiation burden that would allow multiple PET studies on the same subject per year.
Keywords: 13N-ammonia; Whole-body PET/CT; Dosimetry; Tumor

Children with unilateral hydronephrosis are followed up with anteroposterior pelvic diameter (APD), hydronephrosis grade, mercaptoacetyltriglycine (MAG-3) drainage pattern and differential renal function (DRF). Indeterminate drainage preserved DRF in higher grades of hydronephrosis, in some situations, complicating the decision-making process. Due to an asymmetric renal area ratio, falsely negative DRF estimations can result in missed optimal surgery times. This study was designed to assess whether correcting the DRF estimation according to kidney area could reflect the clinical situation of a hydronephrotic kidney better than a classical DRF calculation, concurrently with the hydronephrosis grade, APD and MAG-3 drainage pattern.We reviewed the MAG-3, dimercaptosuccinic acid (DMSA) scans and ultrasonography (US) of 23 children (6 girls, 17 boys, mean age: 29 ± 50 months) with unilateral hydronephrosis. MAG-3 and DMSA scans were performed within 3 months (mean 25.4 ± 30.7 days). The closest US findings (mean 41.5 ± 28.2 days) were used. DMSA DRF estimations were obtained using the geometric mean method. Secondary calculations were performed to correct the counts (the total counts divided by the number of pixels in ROI) according to kidney area. The renogram patterns of patients were evaluated and separated into subgroups. The visual assessment of DMSA scans was noted and the hydronephrotic kidney was classified in comparison to the normal contralateral kidney’s uptake. The correlations of the DRF values of classical and area-corrected methods with MAG-3 renogram patterns, the visual classification of DMSA scan, the hydronephrosis grade and the APD were assessed.DRF estimations of two methods were statistically different (p: 0.001). The categories of 12 hydronephrotic kidneys were changed. There were no correlations between classical DRF estimations and the hydronephrosis grade, APD, visual classification of the DMSA scan and uptake evaluation. The DRF distributions according to MAG-3 drainage patterns were not different. Area-corrected DRF estimations correlated with all: with an increasing hydronephrosis grade and APD, DRF estimations decreased and MAG-3 drainage patterns worsened. A decrease in DRF (<45 %) was determined when APD was ≥10 mm. When APD was ≥26 mm, a reduction of DRF below 40 % was determined.Our results suggest that correcting DRF estimation for asymmetric renal area ratio in unilateral hydronephrosis can be more robust than the classical method, especially for higher grades of hydronephrotic kidneys, under equivocal circumstances.
Keywords: Hydronephrosis; DRF; DMSA; MAG-3; Supranormal function; UPJ; Pelvic diameter

Relationship between fragmented QRS and paradoxical septal motion in coronary artery bypass graft patients by Ahmet Barutçu; Semra Ozdemir; Yusuf Ziya Tan; Ali Ümit Yener; Sedat Özcan; Emine Gazi (825-832).
Paradoxical septal motion (PSM) can cause confusion in the assessment of ventricular function with scintigraphy even in the absence of ventricular septal damage and ischemia. Fragmented QRS (fQRS) is associated with various cardiac disorders. In this study, we aimed to determine the correlation between paradoxical septal motion and fQRS after coronary artery bypass grafting (CABG).We retrospectively reviewed the hospital records showing scintigraphic images and electrocardiograms (ECG) of the patients who had undergone CABG. The patients were classified based on the evaluation of motion and thickening of the septal wall. The patients with regular thickening of the septal wall and abnormal motion were classified as PSM (+) group. The patients with normal motion and thickening of the septal wall were classified as PSM (−) group. fQRS complexes are defined as various RSR patterns either with or without Q-waves on a 12-lead resting ECG.PSM was found to be more common in fQRS patients (p < 0.001). PSM was seen in 91.4 % of cases with fQRS and in 79.8 % of cases without fQRS. No significant differences were found in the phase analysis parameters. A correlation was found between septal wall motion values and the presence of fQRS (r = 0.197, p = 0.012).fQRS was associated with PSM. fQRS may cause PSM in patients with CABG without left bundle branch block due to a conduction defect. PSM and fQRS are predictive of cardiac mortality. Patients diagnosed with PSM and fQRS, should be monitored closely.
Keywords: Paradoxical septal motion; Fragmented QRS; Coronary artery bypass graft

68Ga-DOTATATE uptake in pineal gland, a rare physiological variant: case series by Saima Riaz; Rizwan Syed; Evangelia Skoura; Alshaima Alshammari; Mark Gaze; Rakesh Sajjan; Richard Halsey; Jamshed Bomanji (833-837).
68Ga-DOTATATE PET–CT is widely used for the evaluation of neuroendocrine tumours. Knowledge of the physiological distribution of the radiotracer is of critical importance in characterizing focal areas of uptake. In this case series, we report three paediatric cases (average age 4.7 years ± 0.6 SD) with diagnosed advanced stage IV Neuroblastoma. Two had 68Ga-DOTATATE PET–CT scans and one underwent 68Ga-DOTATATE PET–MRI scan to assess for suitability of molecular therapy. Focal increased tracer uptake in the pineal gland was noted in all cases with no morphological abnormality on the corresponding CT and MRI scans. The uptake within the gland was thought to be a physiological variant rather than metastases owing to the heterogeneity of somatostatin receptors expression. The pineal gland has been reported to express somatostatin receptors. The physiological distribution of 68Ga-DOTATATE uptake in the pineal gland is not routinely seen. Furthermore, the possibility of pineal meningioma is very unlikely as pineal meningiomas are very rare and there was no convincing morphological evidence of meningiomas on CT/MRI scan.
Keywords: Somatostatin receptor; 68Ga-DOTATATE; PET–CT scan; PET–MRI scan; Pineal gland