Annals of Nuclear Medicine (v.24, #5)

Use of PET in the diagnosis of primary CNS lymphoma in patients with atypical MR findings by Nobuyuki Kawai; Shuichi Okubo; Keisuke Miyake; Yukito Maeda; Yuka Yamamoto; Yoshihiro Nishiyama; Takashi Tamiya (335-343).
The diagnosis of primary central nervous system lymphoma (PCNSL) in immunocompetent patients with atypical magnetic resonance (MR) findings such as disseminated lesions or no (non-enhancing) lesion is sometimes difficult because of mimicking other tumorous and non-tumorous diseases. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and 11C-methionine (MET) can measure the glucose and amino acid metabolism in the lesions and may provide useful information for diagnosing PCNSL in patients with such subtle MR findings.We performed PET studies with FDG and MET in 17 histologically proven PCNSL and compared the uptake of FDG and MET qualitatively and quantitatively in the tumors between 12 typical and 5 atypical MR findings.All typical PCNSL showed strong uptake of FDG and MET; however, visual analysis of FDG and MET uptake in atypical PCNSL was not very useful for finding lesions in the brain. Semiquantitative FDG and MET uptake values (SUVmax) and quantitative FDG influx rate constant (K i ) in the tumors are significantly lower in atypical PCNSL compared with those in typical PCNSL. These values obtained in the lesions with atypical MR findings were also not useful for differentiating PCNSL from other tumorous and non-tumorous diseases. The k 3 values evaluated by FDG kinetic analysis in atypical PCNSL were similar to those obtained in typical PCNSL.Visual analysis of FDG and MET uptake in atypical PCNSL was not useful for finding the lesions in the brain. Semiquantitative and quantitative values obtained in the lesions with atypical MR findings were also not useful for differentiating PCNSL from other tumorous and non-tumorous diseases. The k 3 values evaluated by FDG kinetic analysis in atypical PCNSL may provide valuable information in the diagnosis of PCNSL.
Keywords: Fluorodeoxyglucose; Kinetic analysis; Methionine; Primary central nervous system lymphoma; Positron emission tomography

Prospective evaluation of solitary thyroid nodule on 18F-FDG PET/CT and high-resolution ultrasonography by Maria Mathew D’Souza; Raman Kumar Marwaha; Rajnish Sharma; Abhinav Jaimini; Shaji Thomas; Dinesh Singh; Manjula Jain; Param Jit Singh Bhalla; Madhavi Tripathi; Anjani Tiwari; Anil Mishra; Anupam Mondal; Rajendra Prashad Tripathi (345-355).
The utility of 18F-FDG PET/CT in the assessment of thyroid nodules is unclear as there are several conflicting reports on the usefulness of SUV as an indicator to distinguish benign from malignant thyroid lesions. This study incorporated an additional parameter, namely dual time point imaging, to determine the diagnostic accuracy of PET/CT imaging. The performance of 18F-FDG PET/CT was compared to that of high-resolution ultrasound which is routinely used for the evaluation of thyroid nodules.Two hundred patients with incidentally detected solitary thyroid nodules were included in the study. Each patient underwent ultrasound and PET/CT evaluation within 7 days of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively, in a blinded manner. The PET/CT criteria employed were maximum SUV (SUVmax) at 60 min and change in SUVmax at delayed (120 min) imaging. Final diagnosis was based on pathological evaluation and follow-up.Of the 200 patients, 26 had malignant and 174 had benign nodules. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasound were 80.8, 81.6, 39.6, 96.6 and 81.5%, respectively. Using SUVmax at 60 min as the diagnostic criterion, the above indices were 80.8, 84.5, 43.8, 96.7 and 84%, respectively, for PET/CT. The SUVmax of malignant thyroid lesions was significantly higher than benign lesions (16.2 ± 10.6 vs. 4.5 ± 3.1, respectively; p = 0.0001). Incorporation of percentage change in SUVmax at delayed imaging as the diagnostic criterion yielded a slightly improved sensitivity, specificity, PPV, NPV and accuracy of 84.6, 85.6, 46.8, 97.4 and 85.5%, respectively. There was a significant difference in percentage change in SUVmax between malignant and benign thyroid lesions (14.9 ± 11.4 vs. −1.6 ± 13.7, respectively; p = 0.0001). However, there was no statistically significant difference (95% confidence interval) between the diagnostic performance of PET/CT and ultrasound.Routine use of 18F-FDG PET/CT with SUVmax at 60 min as the sole diagnostic criterion does not appear to have a significant advantage over high-resolution ultrasound in the evaluation of thyroid nodules. Incorporation of dual time point imaging enhances image interpretation, and yields a higher diagnostic performance, yet it is not statistically significant. Bearing in mind the cost, limited availability and radiation exposure, routine use of 18F-FDG PET/CT for distinguishing benign from malignant thyroid nodules cannot be recommended.
Keywords: 18F-FDG positron emission tomography/computed tomography; Ultrasonography; Thyroid nodule; Malignant

The objective of this study was to describe the PET/CT findings of mucin-producing non-small cell lung cancer (NSCLC) and how those findings are associated with pathology.A review of all patients with FDG-PET/CT identified 11 patients with histopathologically confirmed mucin-producing NSCLC; 3 mucinous bronchioloalveolar carcinoma (mBAC), 5 mixed-type adenocarcinoma with prominent mucinous BAC pattern (ADENO + mBAC), and 3 mixed-type adenocarcinoma with mucin production (ADENO + MUCIN) in our institute.Among 11 patients, only 2 lesions (18%) evidenced positive PET results for standardized uptake value (SUV) of 3.5 (by ROC analysis) whereas all cases were detected correctly at CT. The mean SUV was 2.0 in the 9 lesions not detected and 2.5 in all cases. The mean SUV of pure mBAC was 1.93, that of mucin-producing adenocarcinoma was 2.69 without a significant difference (p = 0.279). No significant correlations between tumor size or stage and SUV were determined.PET/CT for SUV is limited in the detection of mucin-producing NSCLC. Therefore, the CT component of PET/CT may allow for significantly improved sensitivity and help to reduce delayed diagnose. The SUV in mBACs were lower than the other types of mucin-producing adenocarcinoma; however, we determined no significant difference to exist between the SUVs of two groups of lung cancer.
Keywords: Bronchioloalveolar carcinoma; Adenocarcinoma; PET/CT; Fusion

To investigate the changes in cerebral glucose metabolism in patients with posttraumatic cognitive impairment after memantine therapy.We performed serial F-18 fluorodeoxyglucose positron emission tomography studies before and after memantine therapy (20 mg per day) on 17 patients with posttraumatic cognitive impairment using statistical parametric mapping analysis. In addition, covariance analysis was performed to identify regions, where changes in regional cerebral glucose metabolism correlated significantly with increased Mini-Mental Status Examination scores.Statistical parametric mapping analysis demonstrated that, compared with baseline, significantly increased cerebral glucose metabolism occurred in both inferior, middle and superior frontal gyri, both angular gyri, both precuneus, the right middle cingulum, the left inferior parietal lobule, the left fusiform gyrus, the left precentral gyrus, the left paracentral lobule, and the left lingual gyrus after memantine therapy (P uncorrected < 0.005). In contrast, cerebral glucose metabolism was significantly decreased in both cerebellum, the left thalamus, the left olfactory, the right middle temporal gyrus, the right amygdala, and the right insula (P uncorrected < 0.005). In the correlation analysis, improvements in Mini-Mental Status Examination scores after memantine therapy were significantly associated with increased cerebral glucose metabolism in the inferior and middle frontal gyri and the inferior parietal lobule of the left hemisphere (P corrected < 0.0001).Our findings indicate that the prefrontal and the parietal association cortices may be the relevant structures for the pharmacological response to memantine therapy in patients with posttraumatic cognitive impairment.
Keywords: Cerebral metabolism; Posttraumatic cognitive impairment; Memantine

Clinical implication and prognosis of normal baseline cerebral blood flow with impaired vascular reserve in patients with major cerebral artery occlusive disease by Makoto Isozaki; Yoshikazu Arai; Takashi Kudo; Yasushi Kiyono; Masato Kobayashi; Toshihiko Kubota; Ken-ichiro Kikuta; Hidehiko Okazawa (371-377).
To investigate the prognosis of patients with cerebrovascular steno-occlusive disease who have preserved baseline cerebral blood flow (CBF) and reduced cerebral vasoreactivity (CVR), they were followed up after scans of positron emission tomography (PET).Fifty-seven patients with symptomatic unilateral major cerebral arterial occlusion or severe stenosis underwent O-15 gas and water PET scans to measure cerebral blood volume, metabolic rate of oxygen, oxygen extraction fraction (OEF), and CBF at the baseline and after acetazolamide administration. Thirty of them (mean age 60 ± 10 years) had normal ipsilateral CBF, and were followed prospectively at least 30 months from the last ischemic event. They were medically treated for cerebral circulation and underlying diseases during follow-up periods. The primary endpoint was determined as stroke recurrence during the follow-up.Thirty patients were divided into two groups of reduced CVR (N = 16, 63 ± 8 years) and normal CVR (N = 14, 56 ± 10 years) on the basis of CVR values from healthy volunteers. None of them showed significant laterality in baseline CBF and OEF between the hemispheres although patients with reduced CVR showed a tendency of ipsilateral increases in OEF and CBV. Patients were followed up for 50.5 ± 19.0 and 48.1 ± 12.4 months in the reduced and normal CVR groups, respectively. Although one patient with reduced CVR died of heart disease, there was no incidence of ischemic events during follow-up periods for either group.In the present prospective study, patients with sufficient baseline CBF showed good prognosis and no difference in recurrent stroke risks even though they had poor CVR in the affected hemisphere, indicating that these patients can be treated by medication for cerebral circulation and baseline diseases if they have high risk factors for neurosurgical treatment.
Keywords: Cerebrovascular disease; Long-term prognosis; Cerebrovascular reactivity; Misery perfusion; Cerebral blood flow

Myocardial washout of 99mTc-tetrofosmin and response to steroid therapy in patients with cardiac sarcoidosis by Hirokazu Kudoh; Sei Fujiwara; Hideyuki Shiotani; Hiroya Kawai; Kenichi Hirata (379-385).
Early diagnosis and initiating treatment of cardiac sarcoidosis are essential because cardiac involvement is an important prognostic factor. Although there are many reports on the diagnosis of cardiac sarcoidosis, the literature on predicting the efficacy of steroid therapy is very limited. The purposes of this study were to investigate the myocardial washout of 99mTc-tetrofosmin (TF), and to evaluate the predictability of left ventricular (LV) functional recovery after steroid therapy in patients with cardiac sarcoidosis.We performed TF-gated SPECT and echocardiography for ten patients with cardiac sarcoidosis before and after initiating steroid therapy. SPECT images were acquired at 30 min (early images) and 3 h (delayed images) after injection. We calculated the total defect score (TDS) and left ventricular ejection fraction (LVEF). The washout score (WOS) was considered as the difference between the early and delayed TDS. In addition, we defined ΔLVEF as the change in LVEF after initiating steroid therapy. Furthermore, we analyzed the regional TF myocardial uptake (%uptake) and the regional LV function (wall thickness, WT) by the 20-segment model on polar maps as regional indices. The regional washout (RWO) was defined as the change in %uptake between the early and delayed images in TF SPECT before the therapy. We calculated the improvement factor of the regional LV function as ΔWT (WT after initiating therapy − WT before the therapy) and investigated the relationships among the indices.We observed WO in 6 of 10 patients (60%). Decreased WT on echocardiography was observed in only 2 of 6 patients (33.3%) in the WO(+) group and in all 4 patients (100%) in the WO(−) group (p < 0.05). WOS before initiating steroid therapy exhibited a good correlation with ΔLVEF (r = 0.685, p < 0.05). In the regional analysis, %uptake in the early images and delayed images before therapy did not significantly correlate with ΔWT. In contrast, RWO before therapy was well correlated with ΔWT (r = 0.435, p < 0.05).Our preliminary study shows that there is a relationship between washout of 99mTc-tetrofosmin and the LV functional recovery after steroid therapy in patients with cardiac sarcoidosis.
Keywords: Cardiac sarcoidosis; Washout of 99mTc-tetrofosmin; Left ventricular functional recovery

Estimation of 123I-IMP arterial blood activity from dynamic planar imaging of the chest using a graph plot method for the quantification of regional cerebral blood flow by Seiji Tomiguchi; Kuniyuki Tashiro; Shinya Shiraishi; Morikatsu Yoshida; Koichi Kawanaka; Yoshitake Takahashi; Tsutomu Soma; Yasuyuki Yamashita (387-393).
I-123-labeled N-isopropyl-p-iodoamphetamine (123I-IMP) is used for the measurement of regional cerebral blood flow (rCBF). A continuous or single arterial blood sampling (ABS) is necessary to estimate an integral of arterial input function (AIF) for the measurement of rCBF by using a microsphere model analysis. Therefore, a method of measuring rCBF without any blood sampling is desired. The aim of this study was to establish a method to estimate the AIF from the time–activity curve of the lungs after an injection of 123I-IMP, using a regression analysis for the measurement of rCBF without any blood sampling.Thirty-seven prospective studies in 10 consecutive patients were enrolled. A chest planar dynamic imaging for 3 min and continuous ABS for 5 min after a bolus injection of 167MBq 123I-IMP were performed in all studies. Data from the chest imaging were analyzed in comparison with ABS data (AIF(5)) in the first 10 studies, and an equation for estimation yielding accurate AIF(5) from the total counts cleared from the lungs, during 5 min after injection of 123I-IMP (TCL(5)), was derived. The validity of the proposed method was evaluated in the subsequent 27 studies.A good correlation was obtained between the AIF and TCL by regression analysis in the first 10 studies (r = 0.94, P < 0.001). An equation for the estimation of AIF by the regression analysis in the first 10 studies was defined as follows: estimated AIF = 2147 + 4.174 × TCL(5). In the subsequent 27 studies, a good linear correlation was obtained between the measured and the estimated AIF(5) by using the equation (r = 0.79, P < 0.001).AIF(5) can be accurately estimated from TCL(5). Therefore, estimated AIF(5) can be used for the measurement of rCBF instead of ABS data.
Keywords: CBF measurement; Arterial input function; 123I-IMP; Pulmonary dynamic imaging

Ability of 18F-FDG PET/CT to diagnose recurrent colorectal cancer in patients with elevated CEA concentrations by Yukishige Kyoto; Mitsuru Momose; Chisato Kondo; Michio Itabashi; Shingo Kameoka; Kiyoko Kusakabe (395-401).
Elevated levels of serum carcinoembryonic antigen (CEA) in patients with colorectal cancer (CRC) during follow-up suggest recurrence, which can be visualized by 18F-FDG PET/CT. Since the magnitude of CEA elevation reflects cancer volume, the ability of PET/CT to detect recurrence in patients with only mildly elevated CEA might be limited. However, the accuracy of PET/CT in detecting recurrence associated with elevated CEA has not been fully assessed. We retrospectively evaluated the diagnostic performance of 18F-FDG PET/CT postoperatively relative to CEA levels among patients with CRC.We visually assessed 75 PET/CT evaluations of 57 postoperative patients with CEA >5.0 ng/ml. Tumor volumes were also determined using image analysis software. The final diagnosis was confirmed based on histopathological findings, or at least on 6 months of clinical follow-up.Two lung cancers were excluded and we finally analyzed data from 73 of the 75 PET/CT evaluations. Recurrences were diagnosed in 54 (prevalence 74%). The sensitivity and specificity of PET/CT to detect recurrence was 50/54 (93%) and 14/19 (74%), respectively. The positive and negative predictive values were 91 and 78%, respectively, and the positive and negative likelihood ratios were 3.52 and 0.10, respectively. Values for the sensitivity of PET/CT were 88 and 95%, and those for specificity were 78 and 70%, at serum CEA concentrations of 5–10 and >10 ng/ml, respectively. Serum CEA (r = 0.500, p < 0.001) significantly correlated with cancer volumes.The present findings showed that 18F-FDG PET/CT could accurately detect recurrent CRC irrespective of the elevated CEA concentration.
Keywords: Positron emission tomography (PET); Recurrent colorectal cancer; Carcinoembryonic antigen (CEA); Tumor volume

Synthesis and evaluation of [11C]XR9576 to assess the function of drug efflux transporters using PET by Kazunori Kawamura; Fujiko Konno; Joji Yui; Tomoteru Yamasaki; Akiko Hatori; Kazuhiko Yanamoto; Hidekatsu Wakizaka; Makoto Takei; Nobuki Nengaki; Toshimitsu Fukumura; Ming-Rong Zhang (403-412).
XR9576 (tariquidar) is an anthranilic acid derivative and potent P-glycoprotein (P-gp) inhibitor. XR9576 has undergone phase I and II studies as combined chemotherapy against cancer. XR9576 has been developed as a useful therapeutic agent but not as a PET probe. We therefore developed [11C]XR9576 as a PET probe and assessed whether PET studies using [11C]XR9576 are a promising approach to assess P-gp function primarily.We synthesized [11C]XR9576 by methylation of 7-O-desmethyl XR9576 with [11C]methyl iodide. In in vivo tissue distribution, the effects of co-injection with XR9576 on the uptake of [11C]XR9576 in mice were investigated. PET studies using [11C]XR9576 were performed in P-gp and/or Bcrp knockout mice as well as in wild-type mice. Metabolites of [11C]XR9576 were measured in the brain and plasma of mice.[11C]XR9576 was successfully synthesized with suitable radioactivity for injection as well as appropriate radiochemical purity and stability. In in vivo tissue distribution, the brain uptake of [11C]XR9576 significantly increased about tenfold of control on co-injection with >10 mg/kg of XR9576. In PET studies, the AUCbrain [0–60 min] in P-gp and P-gp/Bcrp knockout mice was 2- and 11-fold higher than that in wild-type mice. [11C]XR9576 showed a high metabolic stability (>90% unchanged form) in the brain and plasma of mice 30 min after injection. These results suggest that a tracer amount of [11C]XR9576 behave as the P-gp and Bcrp substrate, and the increased brain uptake or AUCbrain of [11C]XR9576 correlates with P-gp and Bcrp functions.PET studies using [11C]XR9576 may be a promising approach for evaluating deficiency of the function of drug efflux transporters targeting intracranial diseases and tumors.
Keywords: XR9576; Tariquidar; 11C; P-glycoprotein; Drug efflux transporters; Positron emission tomography (PET)

Optimization of transmission scan duration for 15O PET study with sequential dual tracer administration using N-index by Nobuyuki Kudomi; Hiroshi Watabe; Takuya Hayashi; Hisashi Oka; Yoshinori Miyake; Hidehiro Iida (413-420).
Cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of O2 (CMRO2) can be quantified by PET with the administration of H 2 15 O and 15O2. Recently, a shortening in the duration of these measurements was achieved by the sequential administration of dual tracers of 15O2 and H 2 15 O with PET acquisition and integration method (DARG method). A transmission scan is generally required for correcting photon attenuation in advance of PET scan. Although the DARG method can shorten the total study duration to around 30 min, the transmission scan duration has not been optimized and has possibility to shorten its duration. Our aim of this study was to determine the optimal duration for the transmission scan. We introduced ‘N-index’, which estimates the noise level on an image obtained by subtracting two statistically independent and physiologically equivalent images. The relationship between noise on functional images and duration of the transmission scan was investigated by N-index.We performed phantom studies to test whether the N-index reflects the pixel noise in a PET image. We also estimated the noise level by the N-index on CBF, OEF and CMRO2 images from DARG method in clinical patients, and investigated an optimal true count of the transmission scan.We found tight correlation between pixel noise and N-index in the phantom study. By investigating relationship between the transmission scan duration and N-index value for the functional images by DARG method, we revealed that the transmission data with true counts of more than 40 Mcounts results in CBF, OEF, and CMRO2 images of reasonable quantitative accuracy and quality.The present study suggests that further shortening of DARG measurement is possible by abridging the transmission scan. The N-index could be used to determine the optimal measurement condition when examining the quality of image.
Keywords: Transmission scan; PET; O-15 gas; Image quality

Constrictive tuberculous pericarditis diagnosed using 18F-fluorodeoxyglucose positron emission tomography: a report of two cases by Eleni Testempassi; Kazuo Kubota; Miyako Morooka; Kimiteru Ito; Yoko Masuda-Miyata; Hiroyuki Yamashita; Kenji Ito; Akio Mimori; Hirofumi Kuroki (421-425).
We present two cases of tuberculous pericarditis that were diagnosed using 18F-fluorodeoxyglycose (18F-FDG) positron emission tomography (PET). Here, we highlight the value of 18F-FDG-PET for demonstrating tuberculous pericardial involvement as well as disease dissemination and activity. The patients received antitubercular treatment, and their symptoms and findings resolved accordingly.
Keywords: FDG; PET-CT; Tuberculosis; Pericarditis

Point-like radioactive source with multiple absorber capsules for evaluating PET scanners by Tomoyuki Hasegawa; Eiji Yoshida; Yasushi Sato; Keiichi Oda; Yasuhiro Wada; Takahiro Yamada; Taiga Yamaya; Hideo Murayama; Kyoko Saito (427-432).
Radioactive sources for evaluating sensitivity and uncertainty in the radioactivity measurements performed using PET scanners must be equipped with absorber materials that ensure the annihilation of positrons. Attenuation and scattering owing to the absorber materials produce uncertainty in the performance evaluation. The aim of this study is to propose a point-like radioactive source with multiple absorber capsules, for which evaluation can be independent of scatter and attenuation owing to the source absorbers.The point-like source consists of a small spherical radioactive part and a set of successively sized cylindrical aluminum absorber capsules. Data were collected for different total absorber thicknesses. By an extrapolation technique, the effects of the source absorbers were eliminated. Sensitivity and uncertainty in the radioactivity measurements of PET scanners were evaluated with this technique.Sensitivity and uncertainty of radioactivity measurement to the point-like radioactive source were evaluated successfully with this method.The proposed point-like radioactive source is useful for evaluating performance characteristics of PET scanners in a way that is independent of the effects of the source absorbers.
Keywords: Radioactive source; PET; Performance evaluation