Annals of Nuclear Medicine (v.23, #3)

Positron emission tomography (PET) measurement of cerebral blood flow and metabolism has been a basic and standard method for evaluation of hemodynamics in patients with cerebral vascular disease (CVD). Despite the recent rapid spread of PET and PET/CT facilities, the number of patient examinations with 15O-gas PET scans is declining because most facilities are used for cancer studies. They avoid 15O-gas PET study because it is time consuming and the technique and calculation methods appear to be complicated. However, reconsidering the benefits and usefulness of conventional 15O-gas PET study is a good opportunity to understand its potential possibility. Physiological evaluation of cerebral perfusion and metabolism provided the basic concept of hemodynamics in impaired circulation and the development of evidence-based medicine in neurosurgical treatment for CVD. This method can be used for two major objectives, clinical examination with a less-invasive simplified method, and quantitative precise measurements with model analysis for research purposes. Both are important for developing further practical and investigational approaches using 15O-gas PET.
Keywords: Cerebral blood flow; Cerebral oxygen metabolism; 15O-PET; Cerebral autoregulation; Cerebrovascular reactivity

The relationship between 24 h/4 h radioiodine-131 uptake ratio and outcome after radioiodine therapy in 1402 patients with solitary autonomously functioning thyroid nodules by Mauro Filesi; Laura Travascio; Teresa Montesano; Angelo D. Di Nicola; Marzia Colandrea; Fabio Ugolini; Rocco Bruno; Milton D. Gross; Annarita Vestri; Domenico Rubello; Giuseppe Ronga (229-234).
To evaluate the role of 24 h/4 h uptake ratio (UR) in response to radioiodine-131 (131I) therapy in patients with autonomously functioning thyroid nodules (AFTN).A total of 1402 consecutive hyperthyroid patients were treated with 131I, between 1958 and 2005. Therapeutic doses (D) were calculated according to the formula: D = weight of nodule × dose per gram of nodular tissue (q)/24 h 131I uptake. The ratios of the 24 and 4 h uptake were retrospectively calculated and the patients were grouped according to outcome and q into three groups of UR (≤1.25; 1.26–1.68; ≥1.69) by means of terziles.Of the 1402 patients, 95 did not respond to 131I treatment while 93/1307 developed hypothyroidism. Most non-responders (55.8%) had UR ≤1.25, while many hypothyroid patients (66.7%) had UR ≥1.69 (χ 2: P < 0.001). As q increased, the proportion of successfully treated patients increased (level of significance) only in the group with UR ≤1.25; while in the other two terziles, with increasing dose per gram of nodular tissue, the number of successfully treated patients did not increase (level of significance). The cumulative incidence of hypothyroidism was 2.2% at the 1st year after 131I treatment, increasing to 13.9% at 5 years and 26.2% at 10 years.The 131I UR can predict the outcome of 131I treatment in AFTN and may have utility in modifying treatment in some patients to limit post-radioiodine induced hypothyroidism and treatment failures in order to achieve euthyroidism.
Keywords: Iodine-131; Scintigraphy; Thyrotoxicosis; Therapy thyroid; Radioiodine treatment

Role of carbon-11 choline PET/CT in the management of uterine carcinoma: initial experience by Keitaro Sofue; Ukihide Tateishi; Morio Sawada; Tetsuo Maeda; Takashi Terauchi; Daisuke Kano; Yasuaki Arai; Tomio Inoue; Kazuro Sugimura (235-243).
The present study was conducted to clarify the role of carbon-11 choline (11C-choline) positron emission tomography (PET)/computed tomography (CT) in the management of uterine carcinoma.Twenty-two patients who underwent 11C-choline PET/CT and pelvic MRI were evaluated retrospectively. The images were reviewed by a board-certified radiologist and a nuclear medicine specialist who were unaware of any clinical information, and a consensus was reached. Diagnostic accuracy of PET/CT was evaluated for staging. The reference standard consisted of histological examination (n = 17) and follow-up conventional CT (n = 5). In five patients with cervical carcinoma, 11C-choline PET/CT was performed before and after treatment that consisted of cisplatin infusion and subsequent radiotherapy. Standardized uptake value (SUV) was compared with uni-dimensional and volumetric measurements that were made on magnetic resonance images (MRI) before and after treatment.Based on PET/CT interpretations, the reviewers correctly classified T stage in 8 patients (47%), N stage in 21 patients (96%), M stage in 20 patients (91%), and TNM stage in 15 patients (88%). Tumor size, volume, and SUV decreased after treatment in five patients with cervical carcinoma. Using the Pearson correlation test, a significant correlation was found between the reduction rate of SUV and reduction rate of tumor volume. 11C-choline PET/CT is an accurate means for the management of patients with uterine carcinoma. The combination of 11C-choline PET/CT and MRI increases the accuracy of staging in patients with uterine carcinoma.
Keywords: PET/CT; Choline; Uterine

An anthropomorphic pelvis phantom for optimization of the diagnosis of lymph node metastases in the pelvis by Kazumasa Inoue; Takashi Sato; Hideaki Kitamura; Akira Hirayama; Hideo Kurosawa; Takashi Tanaka; Masahiro Fukushi; Noriyuki Moriyama; Hirofumi Fujii (245-255).
An anthropomorphic pelvis phantom was made by the modification of a National Electrical Manufacturers Association (NEMA) phantom, currently the most popular one, and its clinical usefulness was evaluated.The NEMA plus bone phantom was made by placing the pelvic bone model in the NEMA phantom. The NEMA plus bladder phantom was made by placing an imitation of the urinary bladder in the NEMA phantom. The pelvis phantom was also made by placing both the pelvic bone model and the bladder in the NEMA phantom. Four kinds of phantoms were imaged by both 2D and 3D dynamic modes, and for each phantom, prompt coincidence count rates, random ones, true plus scatter ones, and single photon rates were measured and these coincidence count rates were compared with those from the actual clinical data. After image reconstruction, the contrast ratio and image noise were also investigated.For the random coincidence count rate, the data obtained from each phantom showed good correspondence to the clinical data. The prompt coincidence count rates and true plus scatter ones of the clinical data were different from those obtained from NEMA phantom, NEMA plus bone one and NEMA plus bladder one, whereas there was a good correspondence between the data of the pelvis phantom and the clinical data. For the contrast ratio and image noise, there were discrepancies between the data of NEMA phantom and pelvis phantoms.We made an anthropomorphic pelvis phantom by the simple modification of a NEMA phantom. This phantom showed performance similar to that of the actual human pelvis, suggesting clinical usefulness in the evaluation of new acquisition protocols and reconstruction algorithms.
Keywords: Anthropomorphic phantom; Pelvis; PET; Colorectal cancer; Lymph node

90Y bremsstrahlung emission computed tomography using gamma cameras by Shigeki Ito; Hiroyuki Kurosawa; Hiroyuki Kasahara; Satomi Teraoka; Eiji Ariga; Shizuhiko Deji; Masahiro Hirota; Takuya Saze; Takao Minamizawa; Kunihide Nishizawa (257-267).
This study demonstrates images obtained by 90Y bremsstrahlung emission computed tomography (BECT), and characterizes the system performance of gamma cameras. 90Y BECT images of phantoms were acquired using a gamma camera equipped with a medium energy general purpose parallel-hole collimator. Three energy window widths of 50% (57–94 keV) centered at 75 keV, 30% (102–138 keV) at 120 keV, and 50% (139–232 keV) at 185 keV were set on a 90Y bremsstrahlung spectrum. The images obtained with three energy windows were reconstructed using filtered back projection (FBP) and ordered subsets expectation maximization (OSEM) methods. The images of the sum window were obtained by fusing the images of the 75, 120, and 185 keV windows.The OSEM method improved the full width at half maximum by 20% and the standard deviation by 9% compared with the FBP method. BECT displayed 90Y biodistribution and quantified 90Y activity. BECT images obtained with OSEM method using the 120 keV window showed the highest resolution and lowest uncertainty. The sum window showed the highest sensitivity, while its resolution was 10% inferior to that of the 120 keV window. One whole-body image can be taken over 100 min using the sum window. An absorber to cover the body surface reduced background by 30%. 90Y BECT imaging can be used for patient assessment without modifying current treatment procedures.
Keywords: 90Y-Ibritumomab tiuxetan; 90Y bremsstrahlung; Emission computed tomography; Gamma camera

Relationship between maximum standardized uptake value (SUVmax) of lung cancer and lymph node metastasis on FDG-PET by Atsushi Nambu; Satoshi Kato; Yoko Sato; Hideto Okuwaki; Keiichi Nishikawa; Akitoshi Saito; Keiko Matsumoto; Tomoaki Ichikawa; Tsutomu Araki (269-275).
To evaluate the relationship between SUVmax of primary lung cancers on FDG-PET and lymph node metastasis.The subjects were a total of consecutive 66 patients with lung cancer who were examined by FDG-PET and subsequently underwent surgery between October 2004 and January 2008. There were 41 males and 25 females, ranging in age from 45 to 83 years with an average of 68 years. The pathological subtypes of the lung cancers consisted of 49 adenocarcinomas, 11 squamous cell carcinomas, 2 adenosquamous carcinoma, 1 large cell carcinoma, 1 small cell carcinoma, 1 pleomorphic carcinoma and 1 mucoepidermoid carcinoma. We statistically compared (1) the mean SUVmax of lung cancer between the groups with and without lymph node metastasis (2) the frequency of lymph node metastasis between higher and lower SUVmax of lung cancer groups that were classified by using the median SUVmax of lung cancer, and (3) evaluated the relationship between the SUVmax of lung cancer and frequency of lymph node metastases, and (4) correlations between the SUVmax of lung cancer and number of the metastatic lymph nodes and pathological n stages.The difference in the average of the SUVmax of lung cancer between the cases with and without lymph node metastases was statistically significant (p = 0.00513). Lymph node metastasis was more frequently seen in the higher SUVmax of lung cancer group (17/33, 52%) than in the lower SUVmax of lung cancer group (7/33, 21%) with a statistically significant difference. There was no lymph node metastasis in lung cancers with an SUVmax of lung cancer less than 2.5, and lung cancers with an SUVmax of lung cancer more than 12 had a 70% frequency of lymph node metastasis. There were moderate correlations between SUVmax of lung cancer, and the number of the metastatic lymph nodes (γ = 0.404, p = 0.001) and pathological n stage (γ = 0.411, p = 0.001).The likelihood of lymph node metastasis increases with an increase of the SUV of a primary lung cancer.
Keywords: SUV; FDG-PET; Lung cancer; N-staging; Lymph node

18FDG uptake associated with CT density on PET/CT in lungs with and without chronic interstitial lung diseases by Kentaro Inoue; Ken Okada; Yasuyuki Taki; Ryoi Goto; Shigeo Kinomura; Hiroshi Fukuda (277-281).
The dependent-density of computed tomography (CT) images of positron emission tomography (PET)/CT is sometimes difficult to distinguish from chronic interstitial lung disease (ILD) when it accompanies increased 18F-fluorodeoxy-d-glucose (18FDG) uptake. Though the possible utility of 18FDG-PET for the diagnosis of active ILD has been reported, the clinical relevance of mild lung 18FDG uptake in ILD cases without signs and symptoms suggesting acute progression has not been described. This study aimed to test relationships between 18FDG uptake and lung density on CT using PET/CT in patients with normal lung as well as clinically stable chronic ILD.Thirty-six patients with normal lungs (controls) and 28 patients with chronic ILD (ILD cases) without acute exacerbation were retrospectively selected from 18FDG-PET/CT scans performed in examination of malignant neoplasms. Elliptical regions of interest (ROIs) were placed on the lung. The relationships between CT density and 18FDG uptake between the control and ILD cases were tested.The CT density and 18FDG uptake had a linear correlation in both the controls and the ILD cases without a difference in their regression slopes, and they were overlapped between the controls and the ILD cases with higher mean values in the ILD cases.Lung 18FDG uptake was considered to reflect a gravity-dependent tissue density in the normal lung. Though the lung 18FDG uptake as well as the CT density tended to be higher in chronic ILD patients, it may be difficult to distinguish them in normal dependent regions from those related to chronic ILD in some cases.
Keywords: Computed tomography; Dependent density; 18FDG; Interstitial lung disease; Positron emission tomography

Contribution of subtraction ictal SPECT coregistered to MRI to epilepsy surgery: a multicenter study by Hiroshi Matsuda; Kazumi Matsuda; Fumihiro Nakamura; Shigeki Kameyama; Hiroshi Masuda; Taisuke Otsuki; Hideyuki Nakama; Hiroshi Shamoto; Nobukazu Nakazato; Masahiro Mizobuchi; Joji Nakagawara; Takato Morioka; Yasuo Kuwabara; Hideo Aiba; Masayuki Yano; Yeong-Jin Kim; Hiroyuki Nakase; Ichiei Kuji; Yoko Hirata; Sunao Mizumura; Etsuko Imabayashi; Noriko Sato (283-291).
A multicenter prospective study was performed to assess the additional value of a subtraction ictal SPECT coregistered to MRI (SISCOM) technique to traditional side-by-side comparison of ictal- and interictal SPECT images in epilepsy surgery.One hundred and twenty-three patients with temporal and extratemporal lobe epilepsy who had undergone epilepsy surgery after evaluation of scalp ictal and interictal electroencephalogram (EEG), MRI, and ictal and interictal SPECT scans were followed up in terms of postsurgical outcome for a period of at least 1 year. Three reviewers localized the epileptogenic focus using ictal and interictal SPECT images first by side-by-side comparison and subsequently by SISCOM. Concordance of the localization of the epileptogenic focus by SPECT diagnosis with the surgical site and inter-observer agreement between reviewers was compared between side-by-side comparison and SISCOM. Logistic regression analysis was performed in predicting the surgical outcome with the dependent variable being the achievement of a good postsurgical outcome and the independent variables using the SISCOM, side-by-side comparison of ictal and interictal SPECT images, MRI, and scalp ictal EEG.The SISCOM presented better concordance in extratemporal lobe epilepsy and less concordance in temporal lobe epilepsy than side-by-side comparison. Inter-observer concordance was higher in SISCOM than in side-by-side comparison. Much higher concordance of the epileptogenic focus by SPECT diagnosis with the surgical site was obtained in patients with good surgical outcome than in those with poor surgical outcome. These differences in concordance between good and poor surgical outcomes were greater in SISCOM than in side-by-side comparison. Logistic regression analysis showed the highest odds ratio of 12.391 (95% confidence interval; 3.319, 46.254) by SISCOM evaluation for concordance of the epileptogenic focus with the surgical site in predicting good surgical outcome.A SISCOM technique of ictal and interictal SPECT images provides higher predictive value of good surgical outcome and more reliability on the diagnosis of the epileptogenic focus than side-by-side comparison in medically intractable partial epilepsy.
Keywords: Epilepsy; Ictal SPECT; SISCOM; 99mTc-ECD

De-coupling of blood flow and metabolism in the rat brain induced by glutamate by Shinichiro Hirose; Sotaro Momosaki; Kazunari Sasaki; Rie Hosoi; Kohji Abe; Antony Gee; Osamu Inoue (293-300).
Glutamate plays an essential role in neuronal cell death in many neurological disorders. In this study, we examined both glucose metabolism and cerebral blood flow in the same rat following infusion of glutamate or ibotenic acid using the dual-tracer technique. The effects of MK-801, an NMDA receptor antagonist, and NBQX, an AMPA-kainate receptor antagonist, on the changes in the glucose metabolism and cerebral blood flow induced by glutamate were also examined.The rats were microinjected with glutamate (1 μmol/μl, 2 μl) or ibotenic acid (10 μg/μl, 1 μl) into the right striatum, and dual-tracer autoradiograms of [18F]FDG and [14C]IMP were obtained. MK-801 and NBQX were injected intravenously about 45 and 30 min, respectively, after the infusion of glutamate.De-coupling of blood flow and metabolism was noted in the glutamate-infused hemisphere (as assessed by no alteration of [18F]FDG uptake and significant decrease of [14C]IMP uptake). Pretreatments with MK-801, NBQX, or combined use of MK-801 and NBQX did not affect the de-coupling of the blood flow and metabolism induced by glutamate. A histochemical study revealed that about 20% neuronal cell death had occurred in the striatum at 105 min after the infusion of glutamate. In addition, a significant increase of the [18F]FDG uptake and decrease of [14C]IMP uptake were also seen in the rat brain infused with ibotenic acid.These results indicate that glutamate and ibotenic acid caused a significant de-coupling of blood flow and glucose metabolism in the intact rat brain during the early phase of neurodegeneration. It is necessary to evaluate the relation between metabotropic glutamate receptors and de-coupling of blood flow and metabolism.
Keywords: [18F]FDG; [14C]IMP; Glutamate; Rat; Brain

Preclinical and the first clinical studies on [11C]CHIBA-1001 for mapping α7 nicotinic receptors by positron emission tomography by Jun Toyohara; Muneyuki Sakata; Jin Wu; Masatomo Ishikawa; Keiichi Oda; Kenji Ishii; Masaomi Iyo; Kenji Hashimoto; Kiichi Ishiwata (301-309).
4-[11C]methylphenyl 2,5-diazabicyclo[3.2.2]nonane-2-carboxylate ([11C]CHIBA-1001), a 4-methyl-substituted derivative of the selective α7 nicotinic acetylcholine receptor (α7 nAChR) partial agonist 4-bromophenyl 1,4 diazabicyclo[3.2.2]nonane-4-carboxylate (SSR180711), is a potential radioligand for mapping α7 nAChRs in the brain by positron emission tomography (PET). In this study, we performed preclinical and first clinical PET studies using [11C]CHIBA-1001 for imaging α7 nAChRs in the human brain.[11C]CHIBA-1001 was synthesized by methylation of the tributylstannyl precursor with [11C]CH3I in a palladium-promoted Stille cross-coupling reaction. The radiation absorbed-dose of [11C]CHIBA-1001 in humans was calculated from distribution data in mice. The acute toxicity of CHIBA-1001 at a dose of 3.20 mg/kg body weight, which is more than 41,000-fold the clinical equivalent dose of [11C]CHIBA-1001, was evaluated. The mutagenicity of CHIBA-1001 was studied by a reverse mutation test in Salmonella typhimurium (Ames test). Metabolite analysis in the mouse brain was carried out by high-performance liquid chromatography. The first clinical PET imaging of α7 nAChRs with [11C]CHIBA-1001 in a normal volunteer was also performed.A suitable preparation method for [11C]CHIBA-1001 injection was established. The radiation absorbed-dose by [11C]CHIBA-1001 in humans was low enough for clinical use, and no acute toxicity or mutagenicity of CHIBA-1001 was found. Most radioactivity in the mouse brain was detected as an unchanged form, although peripherally [11C]CHIBA-1001 was degraded. We successfully performed brain imaging by PET with [11C]CHIBA-1001 in a normal volunteer. A 90-min dynamic scan showed a rapid accumulation and gradual washout of radioactivity in the brain. The highest distribution volume of [11C]CHIBA-1001 was found in the thalamus; however, regional differences in brain radioactivity were small. Peripherally, [11C]CHIBA-1001 was stable in humans: >80% of the radioactivity in plasma was detected as the unchanged form for 60 min.These results demonstrate that [11C]CHIBA-1001 is a suitable radioligand to use in clinical trials for imaging α7 nAChRs in the human brain, providing acceptable dosimetry and pharmacological safety at the dose required for adequate PET imaging.
Keywords: α7 Nicotinic receptor; [11C]CHIBA-1001; Central nervous system; Positron emission tomography

Therapeutic effects of acupuncture in patients with rheumatoid arthritis: a prospective study using 18F-FDG–PET by Masami Sato; Masayuki Inubushi; Tohru Shiga; Kenji Hirata; Shozo Okamoto; Tomohito Kamibayashi; Kazuhide Tanimura; Nagara Tamaki (311-316).
The purpose of this study was to investigate whether improvement of regional inflammatory findings in knee joints of rheumatoid arthritis (RA) could be detected by positron-emission tomography (PET) using 18F-Fluorodeoxyglucose (FDG) after acupuncture treatments, as well as improvement of systemic inflammatory markers.Six RA patients (all female, 61 ± 12 years old) received 10 acupuncture treatments in 2 months, to 11 traditional acupuncture points around a knee joint considered effective on RA. A visual analogue scale (VAS) for intensity of pain, knee joint range of motion (ROM), face scale for patient mood, and modified health assessment questionnaire (MHAQ) for disability of daily activities were assessed just before and after acupuncture. Maximum standardized uptake value (SUVmax) and the volume with SUV more than 1.0 [Volume(SUV > 1)] on FDG–PET images as well as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were also measured before and after the treatments.VAS, ROM, face scale and MHAQ improved in all patients and significantly after acupuncture, but no significant change was detected in ESR, CRP, SUVmax, or Volume(SUV > 1).Acupuncture relieves symptom, remedies physical function, and improves quality of life in RA patients, but may have no or very limited anti-inflammatory effect systemically. The regional effects of acupuncture are unlikely to be induced through reduction of regional inflammation. We believe this clinical study is the first step for elucidating therapeutic mechanisms of acupuncture, which must be important for the rational use and further development of acupuncture.
Keywords: Acupuncture; Rheumatoid arthritis; 18F-Fluorodeoxyglucose (18F-FDG); Positron-emission tomography (PET); Treatment outcome

Tc-99m sestamibi parathyroid imaging in a rare case of parathyroid lipoadenoma by Zhaowei Meng; Mingfang Zhang; Jian Tan; Yujie Zhang; Qiang Jia; Fuhai Zhang (317-320).
Parathyroid lipoadenoma is an unusual cause of primary hyperparathyroidism. Only a few earlier reports have documented parathyroid imaging in diagnostic studies of parathyroid lipoadenoma. Our case was a 27-year-old man, who was originally diagnosed with primary hyperparathyroidism. He underwent a Tc-99m sestamibi dual-phase parathyroid imaging study, which revealed a right-inferior parathyroid hyperfunctional lesion. The first operation removed a lesion of 1.5 cm in diameter in the area, and parathyroid lipoadenoma was diagnosed by pathology. However, hypercalcemia persisted. One week later, a Tc-99m sestamibi whole-body scan and another dual-phase imagining were performed, which demonstrated a residual lesion in the inferior part of the right thyroid region, while no ectopic lesion was found. A second surgery was performed and pathological diagnosis was confirmed as parathyroid lipoadenoma again. Our case demonstrated that although hyperfunctional parathyroid lipoadenoma is rare, Tc-99m sestamibi parathyroid imaging is reliable in locating the lesion for surgical purposes. And Tc-99m sestamibi imaging is useful in reoperative and persistent hyperparathyroidism situations as well.
Keywords: Parathyroid lipoadenoma; Tc-99m sestamibi dual-phase parathyroid imaging; Tc-99m sestamibi whole-body scan

PET without cyclotron by Ahmad Mushtaq (321-323).