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Annals of Nuclear Medicine (v.27, #4)
A brief review of Japanese guidelines for the clinical use of 18F-FDG-PET/MRI 2012 (Ver 1.0) by Tomohiro Kaneta (pp. 309-313).
This is a brief review of Japanese FDG-PET/MRI guidelines for indications, procedures, cautions for the interpretation of images, and safety management, which were created by a joint task force of the Japanese Radiologic Society, Japanese Society of Nuclear Medicine, and Japanese Society of Magnetic Resonance Imaging. The guidelines aim at the appropriate and effective use of the newly developed PET/MRI modality.
Keywords: Guideline; FDG; PET/MRI
Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) as a novel amino acid tracer for positron emission tomography by Yasuhiro Ohshima; Hirofumi Hanaoka; Hideyuki Tominaga; Yoshikatsu Kanai; Kyoichi Kaira; Aiko Yamaguchi; Shushi Nagamori; Noboru Oriuchi; Yoshito Tsushima; Keigo Endo; Noriko S. Ishioka (pp. 314-324).
3-[18F]Fluoro-α-methyl-l-tyrosine (l-[18F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because d-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the d-isomer of [18F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) and evaluated its usefulness. d-[18F]FAMT was synthesized according to the method for preparation of l-[18F]FAMT. The in vitro and in vivo stability of [18F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [18F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner.The radiolabeling yield of d-[18F]FAMT was approximately 10 %, similar to that of l-[18F]FAMT. Over 95 % of d-[18F]FAMT remained intact in mice until 60 min after administration. d-[18F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of d-[18F]FAMT was competitively inhibited by pretreatment with α-methyl-l-tyrosine, a selective substrate for the system l-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of d-[18F]FAMT. In biodistribution studies, d-[18F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to l-[18F]FAMT. The amount of d-[18F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of d-[18F]FAMT were similar to those of l-[18F]FAMT at every time point. PET imaging with d-[18F]FAMT did not provide a clear image of the tumor early after administration. However, d-[18F]FAMT provided higher tumor-to-background contrast than l-[18F]FAMT. d-[18F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with l-[18F]FAMT. Thus, d-[18F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.
Keywords: 3-[18F]Fluoro-α-methyl-l-tyrosine (l-[18F]FAMT); 3-[18F]Fluoro-α-methyl-d-tyrosine (d-[18F]FAMT); Positron emission tomography (PET); Amino acid tracer; Tumor
Phase analysis by gated F-18 FDG PET/CT for left ventricular dyssynchrony assessment: a comparison with gated Tc-99m sestamibi SPECT by Li Wang; Hong-Xing Wei; Min-Fu Yang; Jin Guo; Jian-Feng Wang; Wei Fang; Yue-Tao Wang (pp. 325-334).
To investigate the value of gated F-18 FDG PET/CT on left ventricular (LV) dyssynchrony assessment in comparison with gated Tc-99m sestamibi SPECT in patients with coronary artery disease (CAD).The data of 100 consecutive CAD patients who underwent both gated myocardial Tc-99m sestamibi SPECT and F-18 FDG PET/CT imaging were analyzed. Phase standard deviation (SD) and histogram bandwidth (BW) were derived from phase analysis using Cedars software package. The correlation and agreement of SD and BW between Tc-99m sestamibi SPECT and F-18 FDG PET/CT were examined. Myocardial viability and the site of latest activation assessed by the two imaging methods were compared as well.A moderate correlation for SD (r = 0.58, p < 0.0001) and BW (r = 0.60, p < 0.0001) was found between gated SPECT and gated F-18 FDG PET/CT. Bland–Altman analysis revealed an overestimation of SD and BW (6.4° ± 14.3° and 22.0° ± 46.8°) by gated F-18 FDG PET/CT. Multivariate logistic regression analysis identified that significant LV remodeling on SPECT imaging, LV functional parameters and F-18 FDG uptake ratio of myocardium to blood pool (SUVM/B) were associated with the overestimation. Myocardial SPECT and F-18 FDG PET/CT had a 67.1 % identity in determining the latest activation site and 5.2 % more viable myocardium was detected by F-18 FDG PET/CT than SPECT.Gated F-18 FDG PET/CT moderately correlated with gated Tc-99m sestamibi SPECT in assessing LV dyssynchrony. Gated F-18 FDG PET/CT phase analysis should be cautiously applied in CAD patients with significant LV remodeling on SPECT imaging, severe LV functional impairment or poor myocardial F-18 FDG uptake.
Keywords: Gated; F-18 FDG; PET/CT; SPECT; Phase analysis; Left ventricular dyssynchrony
Impact of subject head motion on quantitative brain 15O PET and its correction by image-based registration algorithm by Keisuke Matsubara; Masanobu Ibaraki; Kazuhiro Nakamura; Hiroshi Yamaguchi; Atsushi Umetsu; Fumiko Kinoshita; Toshibumi Kinoshita (pp. 335-345).
Subject head motion during sequential 15O positron emission tomography (PET) scans can result in artifacts in cerebral blood flow (CBF) and oxygen metabolism maps. However, to our knowledge, there are no systematic studies examining this issue. Herein, we investigated the effect of head motion on quantification of CBF and oxygen metabolism, and proposed an image-based motion correction method dedicated to 15O PET study, correcting for transmission–emission mismatch and inter-scan mismatch of emission scans.We analyzed 15O PET data for patients with major arterial steno-occlusive disease (n = 130) to determine the occurrence frequency of head motion during 15O PET examination. Image-based motion correction without and with realignment between transmission and emission scans, termed simple and 2-step method, respectively, was applied to the cases that showed severe inter-scan motion.Severe inter-scan motion (>3 mm translation or >5° rotation) was observed in 27 of 520 adjacent scan pairs (5.2 %). In these cases, unrealistic values of oxygen extraction fraction (OEF) or cerebrovascular reactivity (CVR) were observed without motion correction. Motion correction eliminated these artifacts. The volume-of-interest (VOI) analysis demonstrated that the motion correction changed the OEF on the middle cerebral artery territory by 17.3 % at maximum. The inter-scan motion also affected CBV, CMRO2 and CBF, which were improved by the motion correction. A difference of VOI values between the simple and 2-step method was also observed.These data suggest that image-based motion correction is useful for accurate measurement of CBF and oxygen metabolism by 15O PET.
Keywords: Cerebral blood flow; Cerebral oxygen metabolism; Oxygen-15; Positron emission tomography; Subject motion artifact
Validation of novel calibration scheme with traceable point-like 22Na sources on six types of PET scanners by Tomoyuki Hasegawa; Keiichi Oda; Yasuhiro Wada; Toshiaki Sasaki; Yasushi Sato; Takahiro Yamada; Mikio Matsumoto; Hideo Murayama; Kei Kikuchi; Hiroki Miyatake; Yutaka Abe; Kenta Miwa; Kenta Akimoto; Kei Wagatsuma (pp. 346-354).
To improve the reliability and convenience of the calibration procedure of positron emission tomography (PET) scanners, we have been developing a novel calibration path based on traceable point-like sources. When using 22Na sources, special care should be taken to avoid the effects of 1.275-MeV γ rays accompanying β + decays. The purpose of this study is to validate this new calibration scheme with traceable point-like 22Na sources on various types of PET scanners.Traceable point-like 22Na sources with a spherical absorber design that assures uniform angular distribution of the emitted annihilation photons were used. The tested PET scanners included a clinical whole-body PET scanner, four types of clinical PET/CT scanners from different manufacturers, and a small-animal PET scanner. The region of interest (ROI) diameter dependence of ROI values was represented with a fitting function, which was assumed to consist of a recovery part due to spatial resolution and a quadratic background part originating from the scattered γ rays.The observed ROI radius dependence was well represented with the assumed fitting function (R 2 > 0.994). The calibration factors determined using the point-like sources were consistent with those by the standard cross-calibration method within an uncertainty of ±4 %, which was reasonable considering the uncertainty in the standard cross-calibration method.This novel calibration scheme based on the use of traceable 22Na point-like sources was successfully validated for six types of commercial PET scanners.
Keywords: Calibration; Point-like source; Traceability; Quality control
Monitoring tumor proliferative response to radiotherapy using 18F-fluorothymidine in human head and neck cancer xenograft in comparison with Ki-67 by Chowdhury Nusrat Fatema; Songji Zhao; Yan Zhao; Masahiro Murakami; Wenwen Yu; Ken-ichi Nishijima; Nagara Tamaki; Yoshimasa Kitagawa; Yuji Kuge (pp. 355-362).
Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using 18F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT.FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. 3H-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral 3H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed.In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral 3H-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral 3H-FLT level markedly decreased to 45 and 40 % of the control, respectively (P < 0.0001 vs control), and then gradually increased with time. In each radiation-treated group, the 3H-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral 3H-FLT levels in both treated groups were 68 and 60 % at 24 h (P < 0.001), 71 and 77 % at 48 h (P < 0.001), and 83 and 81 % on day 7 (P = NS) compared with the control group.Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time. Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer.
Keywords: 18F-fluorothymidine; Radiotherapy; Tumor proliferation; Ki-67 labeling index; Head and neck cancer xenograft
Changes in 18F-fluorothymidine and 18F-fluorodeoxyglucose positron emission tomography imaging in patients with head and neck cancer treated with chemoradiotherapy by Hiroshi Hoshikawa; Terushige Mori; Takehito Kishino; Yuka Yamamoto; Ryuhei Inamoto; Kosuke Akiyama; Nozomu Mori; Yoshihiro Nishiyama (pp. 363-370).
This study compared change of 18F-fluorothymidine (FLT) uptake with that of 18F-fluorodeoxyglucose (FDG) in head and neck squamous cell cancer (HNSCC) patients during and after treatment and evaluated the utility for early monitoring of response to chemoradiotherapy.Thirty patients with newly diagnosed HNSCCs treated with concurrent chemoradiotherapy underwent FLT and FDG PET in pre-treatment (PET1), mid-treatment (PET2) and post-treatment (PET3) stages. The PET images were evaluated quantitatively using maximum standardized uptake values (SUVs). Ratios between SUVs at PET2 and PET3 were also calculated.According to the SUVs, no significant differences were found with primary site location, cellular differentiation and T category in all PET scans. About a 78 % median decrease in FLT SUV was observed at the total dose (TD) of 30 Gy and no apparent change was observed thereafter. About a 40 % decrease in FDG SUV was observed at TD 30 Gy and significant decreases were then found at the 4- and 6-week time points after the therapy. FLT PET demonstrated no recurrence regions in patients with a PET3/PET2 ratio of <1.5. In comparison, FLT SUVs in PET3 with recurrence were increased more than three times. However, no significant difference was found between the values with recurrence and those with no recurrence in FDG PET.FLT PET signal change preceded FDG PET change and the increase of FLT uptake after the therapy can imply recurrence or a residual tumor. FLT PET seems promising for early evaluation of chemoradiation effects in HNSCCs.
Keywords: FLT PET; FDG PET; SUVs; Chemoradiation; Early prediction
Discordance in the anatomical locations between morphological and perfusion changes occurring with the progression of Alzheimer’s disease by Koji Ogomori; Satoru Majima; Yasuo Kuwabara; Koichi Takano; Masanari Nonokuma; Kengo Yoshimitsu; Ryoji Nishimura (pp. 371-377).
The aim of this study was to clarify the difference between the morphological and perfusion changes occurring with the progression of Alzheimer’s disease (AD).The study focused on 37 patients who were clinically diagnosed with AD and were examined by both MRI and perfusion SPECT twice during a 1- to 2-year clinical observation period. Twenty-four of the 37 patients showed a progression of cognitive deterioration during the 1.2(±0.4)-year period of clinical observation (rapidly progressing group: initial mean MMSE score = 23.3; second mean MMSE score = 20.2), while 13 patients showed no apparent progression of cognitive deterioration (slowly progressing group: initial mean MMSE score = 21.2; second mean MMSE score = 22.2). The morphological changes were evaluated using a voxel-based morphometric technique with segmented MRI images. Cerebral perfusion was measured by Tc-99m ECD SPECT. Data analysis was performed by SPM on a MATLAB work space (2007.a).There was no significant difference in either the perfusion or gray matter density between the rapidly progressing and slowly progressing groups at the initial examination. The rapidly progressing group showed an interval decrease of perfusion in the bilateral parieto-occipital cortex and a decrease of gray matter density in the bilateral temporal and cingulate cortex. The slowly progressing group did not show a significant interval change in either the cerebral perfusion or gray matter density.These results suggest that rapid symptomatic progression in AD patients accompanies rapid progression of both morphological and perfusion changes, although the regions of the changes differ between them.
Keywords: Alzheimer’s disease; MRI; Voxel-based morphometry; SPECT; Perfusion; Longitudinal study
The possible role of nuclear imaging in assessment of the cardiac resynchronization therapy effectiveness in patients with moderate heart failure by Yuri Lishmanov; Stanislav Minin; Irina Efimova; Vladimir Chernov; Yulia Saushkina; Denis Lebedev; Sergey Popov (pp. 378-385).
The aim of the study was to elucidate the role of nuclear medicine imaging in the selection of candidates for cardiac resynchronization therapy (CRT) and in the evaluation of CRT effectivenessWe studied 28 patients (19 male and 9 female) with dilated cardiomyopathy (DCM) and heart failure (HF). Before implantation of CRT device, all patients underwent SPECT with 99mTc-MIBI at rest to evaluate the myocardial perfusion, 123I-BMIPP to evaluate the myocardial metabolism, and gated cardiac blood-pool SPECT (GBPS) to assess the myocardial contractile function. Following CRT, all patients were examined with 99mTc-MIBI SPECT and GBPS 12 ± 3 months after the intervention.All patients after CRT were divided into three groups. The first group included 10 patients with LVEF increased by more than 10 % (hyperresponders), the 2nd group included 11 patients with an increase in EF of more than 5 % but less than 10 % (responders) and third group consisted of 7 males whose LVEF remained unchanged or worsened compared with pre-operative values (nonresponders). Prior to CRT, no statistically significant differences were found between groups in hemodynamic parameters (EF, EDV, ESV, SV), intra- and interventricular dyssynchrony, as well as in the midsize of perfusion defects. Following long-term CRT, we found increase in LVEF and decrease in average size of perfusion defects in groups of hyperresponders and responders (p < 0.05). Results of SPECT with 123I-BMIPP, performed prior to CRT, showed that nonresponders had more pronounced disturbance of myocardial metabolism compared with the group of hyperresponders (20 vs. 14.7 %, p < 0.05).The radionuclide methods can be used as possible indicators in the evaluation effectiveness and selection of candidates on the CRT.
Keywords: Cardiac resynchronization therapy; Nuclear imaging; Heart failure
Symptomatic late-onset sialadenitis after radioiodine therapy in thyroid cancer by Young-Sil An; Joon-Kee Yoon; Su Jin Lee; Hee-Sung Song; Seok-Ho Yoon; Kyung-Sook Jo (pp. 386-391).
The aim of this study was to document the subjective and objective findings of symptomatic late-onset sialadenitis after radioiodine therapy in patients with differentiated thyroid cancer.Subjective symptoms related to sialadenitis and Tc-99m pertechnetate salivary gland scintigram findings were assessed in 118 patients (26 males, 92 females) both before and during the late phase (mean 338 days) after the administration of radioiodine.Twelve of the 118 patients (10.2 %) complained of symptomatic sialadenitis in the late phase without symptoms during the early phase (within 7 days of radioiodine administration). Significant associations were found between subjective symptoms and visual scintigram findings during the late phase (p = 0.023). Furthermore, uptake and excretion by both parotid glands were significantly affected by radioiodine therapy.Symptomatic late-onset sialadenitis occurred at an incidence of 10.2 %, and salivary gland function was affected in both parotids in most patients.
Keywords: Radioiodine therapy; Thyroid cancer; Salivary gland; Sialadenitis; Salivary gland scintigram; Late-onset
Assessment of FDG retention differences between the FDG-avid benign pulmonary lesion and primary lung cancer using dual-time-point FDG-PET imaging by Koichiro Kaneko; Shinji Sadashima; Koji Irie; Akihiro Hayashi; Satoru Masunari; Tsuyoshi Yoshida; Junichi Omagari (pp. 392-399).
The aim of this study was to clarify FDG retention differences between FDG-avid benign pulmonary lesions (BPLs) and primary lung cancers (PLCs), and between tuberculous and non-tuberculous BPLs using dual-time-point FDG-PET imaging.Thirty-four BPLs and 47 PLCs with a maximal standardized uptake value (SUVmax) >2.5 and a maximal axial diameter >10 mm were enrolled. We compared the retention index (RI) among different types of lesions, and evaluated the relationship between RI and SUVmax at 1 h (SUV1). Glucose transporter-1 (Glut-1) and hexokinase (HK)-2 expression was assessed in eight non-tuberculous BPLs.BPLs and PLCs showed similar high RIs (mean ± SD 33.6 ± 22.6 and 32.5 ± 23.7, respectively; p = 0.95). In BPLs, both tuberculous and non-tuberculous lesions showed high RIs (39.1 ± 25.8 and 30.3 ± 20.3, respectively; p = 0.43). However, BPLs and PLCs exhibited a different relationship between RI and SUV1. BPLs tended to show lower RIs with higher SUV1s, and a mild negative correlation, whereas PLCs showed persistent high RIs and no significant correlation. Glut-1 and HK-2 expression was found in 75 and 12.5 % of non-tuberculous BPLs, respectively.FDG-avid BPLs could show high RIs regardless of their being tuberculous and non-tuberculous lesions, and no significant difference with PLC RIs was found. FDG-avid BPLs and PLCs showed different relationships between RI and SUV1, and it seemed to be related with different mechanisms of high FDG retention. However, the mechanisms of high FDG retention in FDG-avid BPLs remain unclear, and this matter requires further investigation.
Keywords: FDG-avid benign pulmonary lesion; Primary lung cancer; FDG retention; Dual-time-point FDG-PET imaging
FDG PET/CT evaluation of pathologically proven pulmonary lesions in an area of high endemic granulomatous disease by Ronnie Sebro; Carina Mari Aparici; Miguel Hernandez-Pampaloni (pp. 400-405).
The goal of this study is to assess how reliable the threshold maximum standardized uptake value (maxSUV) of 2.5 on positron emission tomography–computed tomography (PET/CT) is for evaluation of solitary pulmonary lesions
Keywords: in an area of endemic granulomatous disease and to consider other imaging findings that may increase the accuracy of PET/CT.The staging PET/CT of 72 subjects with solitary pulmonary lesions (nodules (less than 3 cm) or masses (greater than 3 cm)) were retrospectively reviewed. Pathology proven diagnosis from tissue samples was used as the gold standard. Logistic regression was used to assess whether the subject’s age, maxSUV, size of lesion, presence of emphysema, or evidence of granulomatous disease was predictive of malignancy.Malignant lesions were identified in 84.7 % (61/72) of the 72 subjects. A threshold maxSUV of 2.5 had a sensitivity of 95.1 % (58/61), specificity of 45.5 % (5/11), positive predictive value of 90.6 % (58/64), negative predictive value of 62.5 % (5/8) and an accuracy of 87.5 % (63/72). The false negative rate was 4.9 %, and the false positive rate was 54.5 %. All 3 false negatives were less than or equal to 1.0 cm; however, false positives ranged from 1.1 to 5.6 cm. The false negatives had a mean (SD) maxSUV of 2.0 (0.4), whereas the false positives had a mean (SD) maxSUV of 5.6 (3.0). Emphysema was associated with 1.1 higher odds of malignancy, and evidence of granulomatous disease was associated with 0.34 lower odds of benign disease, however, neither was statistically significant (p = 0.92 and p = 0.31, respectively). Higher maxSUV was significantly associated with increased risk of malignancy (p = 8.3 × 10−3). Older age and larger size of lesion were borderline associated with increased risk of malignancy (p = 0.05 and p = 0.07, respectively).In an area of high endemic granulomatous disease, the PET/CT threshold maxSUV of 2.5 retains a high sensitivity (95.1 %) and positive predictive value (90.6 %) for differentiating benign from malignant pulmonary lesions; however, the specificity (45.5) and negative predictive value (62.5) decrease due to increased false positives. The presence of emphysema and absence of evidence of granulomatous disease increases the probability that a pulmonary lesion is malignant; however, these were not statistically significant.