Annals of Nuclear Medicine (v.31, #7)

18F-fluorothymidine PET imaging in gliomas: an update by Alexandra Nikaki; George Angelidis; Roxani Efthimiadou; Ioannis Tsougos; Varvara Valotassiou; Konstantinos Fountas; Vasileios Prasopoulos; Panagiotis Georgoulias (495-505).
Brain neoplasms constitute a group of tumors with discrete differentiation grades, and therefore, course of disease and prognosis. Magnetic resonance imaging (MRI) remains the gold standard method for the investigation of central nervous system tumors. However, MRI suffers certain limitations, especially if radiation therapy or chemotherapy has been previously applied. On the other hand, given the development of newer radiopharmaceuticals, positron emission tomography (PET) aims to a better investigation of brain tumors, assisting in the clinical management of the patients. In the present review, the potential contribution of radiolabeled fluorothymidine (FLT) imaging for the evaluation of brain tumors will be discussed. In particular, we will present the role of FLT-PET imaging in the depiction of well and poorly differentiated lesions, the assessment of patient prognosis and treatment response, and the recognition of disease recurrence. Moreover, related semi-quantitative and kinetic parameters will be discussed.
Keywords: Fluorothymidine; Glioma; MRI; PET; Prognosis

[18F]FP-(+)-DTBZ PET study in a lactacystin-treated rat model of Parkinson disease by Chi-Chang Weng; Siao-Lan Huang; Zi-An Chen; Kun-Ju Lin; Ing-Tsung Hsiao; Tzu-Chen Yen; Mei-Ping Kung; Shiaw-Pyng Wey; Ching-Han Hsu (506-513).
Lactacystin has been used to establish rodent models of Parkinson disease (PD), with cerebral α-synuclein inclusions. This study evaluated the uptake of [18F]9-fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ), a vesicular monoamine transporter type 2 (VMAT2)-targeting radiotracer, through positron emission tomography (PET) in lactacystin-treated rat brains.Adult male Sprague–Dawley rats were randomly treated with a single intracranial dose of lactacystin (2 or 5 μg) or saline (served as the sham control) into the left medial forebrain bundle. A 30-min static [18F]FP-(+)-DTBZ brain PET scan was performed following an intravenous [18F]FP-(+)-DTBZ dose (approximately 22 MBq) in each animal at 2 and 3 weeks after lactacystin treatment. Upon completing the last PET scans, the animals were killed, and their brains were dissected for ex vivo autoradiography (ARG) and immunohistochemical (IHC) staining of tyrosine hydroxylase (TH) as well as VMAT2.Both the 2- and 5-μg lactacystin-treated groups exhibited significantly decreased specific [18F]FP-(+)-DTBZ uptake in the ipsilateral striata (I-ST) at 2 weeks (1.51 and 1.16, respectively) and 3 weeks (1.36 and 1.00, respectively) after lactacystin treatment, compared with the uptake in the corresponding contralateral striata (C-ST) (3.48 and 3.08 for the 2- and 5-μg lactacystin-treated groups, respectively, at 2 weeks; 3.36 and 3.11 for the 2- and 5-μg lactacystin-treated groups, respectively, at 3 weeks) and the sham controls (3.34–3.53). Lactacystin-induced decline in I-ST [18F]FP-(+)-DTBZ uptake was also demonstrated through ex vivo ARG, and the corresponding dopaminergic neuron damage was confirmed by the results of TH- and VMAT2-IHC studies.In this PD model, lactacystin-induced dopaminergic terminal damage in the ipsilateral striatum could be clearly visualized through in vivo [18F]FP-(+)-DTBZ PET imaging. This may serve as a useful approach for evaluating the effectiveness of new treatments for PD.
Keywords: Parkinson disease; Animal model; Lactacystin; PET imaging; Autoradiography

FDG-PET/CT predicts survival and lung metastasis of hypopharyngeal cancer in a multi-institutional retrospective study by Hidenori Suzuki; Katsuhiko Kato; Masami Nishio; Tsuneo Tamaki; Yasushi Fujimoto; Mariko Hiramatsu; Nobuhiro Hanai; Takeshi Kodaira; Yoshiyuki Itoh; Shinji Naganawa; Michihiko Sone; Yasuhisa Hasegawa (514-520).
We investigated a possible correlation between the maximum standardized uptake value (SUVmax), which is assessed by pretreatment 18F-fluorodeoxyglucose positron emission tomography with computed tomography, and the overall survival (OS) in patients with hypopharyngeal squamous cell carcinoma from two institutions on long-term follow-up, and examined whether SUVmax is correlated with several survival outcomes, including lung metastasis-free survival.A total of 81 patients were enrolled. The survival rate was calculated by the Kaplan–Meier method. Both univariate and multivariate survival analyses were assessed by a Cox proportional hazards model.SUVmax ≥15.2 in institution A (p = 0.0306) or SUVmax ≥8 in institution B (p = 0.0132) was significantly predictor of a lower OS. We disaggregated the data by high SUVmax (SUVmax ≥15.2 from institution A and SUVmax ≥8 from institution B) and low SUVmax (SUVmax <15.2 from institution A and SUVmax <8 from institution B). Patients with a high SUVmax exhibited a significantly lower OS in both univariate (p = 0.001) and multivariate (p = 0.0046) analyses for adjusted for the clinical stage and treatment group. The patients with a high SUVmax exhibited significantly shorter disease-specific (p = 0.0068), distant metastasis-free (p = 0.0428), and lung metastasis-free (p = 0.0328) survivals.High SUVmax was significantly correlated with a lower OS, disease-specific survival, distant metastasis-free survival, and lung metastasis-free survival in a multi-institutional retrospective study.
Keywords: Hypopharyngeal squamous cell carcinoma; 18F-FDG-PET/CT; SUVmax ; Overall survival; Lung metastasis

The computer-assisted diagnostic system for bone scintigraphy (BS) BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic performance in prostate cancer patients with and without skeletal metastasis and searched for the problems.An artificial neural network (ANN) value was calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101 without) using BS. Receiver operating characteristic curve analysis was performed and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient’s situation at the time of diagnosis of skeletal metastasis, computed tomography (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False-negative and false-positive results were recorded.BONENAVI showed 82% (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection. There were no significant differences among CT types, although low EOD and faint BS uptake were associated with low ANN values and low sensitivity. Patients showed lower sensitivity during the follow-up period than staging work-up. False-negative lesions were often located in the pelvis or adjacent to it. They comprised not only solitary, faint BS lesions but also overlaying to urinary excretion.BONENAVI with BS has good sensitivity and specificity for detecting prostate cancer’s osseous metastasis. Low EOD and faint BS uptake are associated with low sensitivity but not the CT type. Prostate cancer patients likely to have false-negative results during the follow-up period had a solitary lesion in the pelvis with faint BS uptake or lesions overlaying to urinary excretion.
Keywords: Computer-assisted diagnosis; Bone scintigraphy; Bone metastasis; Prostate cancer

Characteristics of single- and dual-photopeak energy window acquisitions with thallium-201 IQ-SPECT/CT system by Takayuki Shibutani; Masahisa Onoguchi; Hiroto Yoneyama; Takahiro Konishi; Shinro Matsuo; Kenichi Nakajima; Seigo Kinuya (529-535).
Although dual-energy (DE) acquisition with conventional 201Tl myocardial perfusion SPECT has several advantages such as improved attenuation of the inferior wall and increased acquisition counts, the characteristics of IQ-SPECT have not been fully evaluated. We evaluate the difference of characteristics between single-energy (SE) and dual-energy (DE) imaging using 201Tl myocardial IQ-SPECT.Two myocardial phantoms were created simulating normal myocardium and infarction of the inferior wall. Energy windows were set at 70 keV ± 10% for SE, and an additional 167 keV ± 7.5% for DE. SPECT images were reconstructed using the ordered subset conjugates gradient minimizer (OSCGM) method. We visually and quantitatively compared short-axis images of correction for no (NC), for attenuation (AC) or for both AC and scatter (ACSC) images.The average counts of SE and DE projection data were 17.5 and 20.3 counts/pixel, respectively. The DE data increased acquisition counts by approximately 16% compared with the SE data. The average visual score of normal myocardium did not differ significantly between the SE and DE images. However, the DE image of defective myocardium showed a significantly lower score in AC than SE images. The % uptake values of DE image with both NC and AC were significantly higher than those of SE images. The DE images of the inferior defective areas (segments 4 and 10) showed approximately 5–10% higher uptake compared with the SE images.The DE image with NC improved attenuation of the inferior wall. However, DE image with AC showed low defect detectability. Thus, AC should be used with SE rather than DE. Furthermore, while the SE image with ACSC can be used to detect perfusion defects, it must be interpreted carefully including the possibility of artificial inhomogeneity even in the normal myocardium.
Keywords: IQ-SPECT; 201Tl myocardial perfusion SPECT; Energy window; Computed tomography-based attenuation correction; Phantom study

Validation of the cingulate island sign with optimized ratios for discriminating dementia with Lewy bodies from Alzheimer’s disease using brain perfusion SPECT by Etsuko Imabayashi; Tsutomu Soma; Daichi Sone; Tadashi Tsukamoto; Yukio Kimura; Noriko Sato; Miho Murata; Hiroshi Matsuda (536-543).
Dementia with Lewy bodies (DLB) is often cited as the second most common dementia after Alzheimer’s disease (AD). It is clinically important to distinguish DLB from AD because specific side effects of antipsychotic drugs are limited to DLB. The relative preservation of cingulate glucose metabolism in the posterior cingulate gyri versus that in the precuni, known as the cingulate island sign (CIS), in patients with DLB compared with AD is supposed to be highly specific for diagnosing DLB. In a previous study, using brain perfusion SPECT, the largest value (0.873) for the area under the receiver operating characteristic (ROC) curve (AUC) for differentiating DLB from AD was obtained with the ratio of the posterior cingulate gyri from an early Alzheimer’s disease-specific hypoperfusion volume of interest (VOI) versus the medial occipital lobe. Two purposes of this study are as follows: one is optimization of VOI setting for calculating CIS values and the other is to evaluate their accuracy and simultaneously to retest the method described in our previous paper.We conducted a retest of this SPECT method with another cohort of 13 patients with DLB and 13 patients with AD. Furthermore, we optimized VOIs using contrast images obtained from group comparisons of DLB and normal controls; the same 18 patients with DLB and 18 normal controls examined in our previous study. We obtained DLB-specific VOIs from areas where brain perfusion was significantly decreased in DLB. As the numerators of these ratios, early Alzheimer’s disease-specific VOIs were used after subtracting DLB-specific VOIs. The DLB-specific VOIs were used as the denominator.In retest, the obtained AUC was 0.858 and the accuracy, sensitivity, and specificity were 84.6, 84.6, and 84.6%, respectively. The ROC curve analysis with these optimized VOIs yielded a higher AUC of 0.882; and the accuracy, sensitivity, and specificity of these new CIS ratios were 84.6, 92.3, and 76.9%, respectively, with a threshold value of 0.281.Optimized CISs using brain perfusion SPECT are clinically useful for differentiating DLB from AD.
Keywords: Brain perfusion SPECT; CIS; DLB; Alzheimer’s disease

Textural features of 18F-FDG PET after two cycles of neoadjuvant chemotherapy can predict pCR in patients with locally advanced breast cancer by Lin Cheng; Jianping Zhang; Yujie Wang; Xiaoli Xu; Yongping Zhang; Yingjian Zhang; Guangyu Liu; Jingyi Cheng (544-552).
This study was designed to evaluate the utility of textural features for predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC).Sixty-one consecutive patients with locally advanced breast cancer underwent 18F-FDG PET/CT scanning at baseline and after the second course of NAC. Changes to imaging parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG)] and textural features (entropy, coarseness, skewness) between the 2 scans were measured by two independent radiologists. Pathological responses were reviewed by one pathologist, and the significance of the predictive value of each parameter was analyzed using a Chi-squared test. Receiver operating characteristic curve analysis was used to compare the area under the curve (AUC) for each parameter.pCR was observed more often in patients with HER2-positive tumors (22 patients) than in patients with HER2-negative tumors (5 patients) (71.0 vs. 16.7%, p < 0.001). ∆ %SUVmax, ∆ %entropy and ∆ %coarseness were significantly useful for differentiating pCR from non-pCR in the HER2-negative group, and the AUCs for these parameters were 0.928, 0.808 and 0.800, respectively (p = 0.003, 0.032 and 0.037). In the HER2-positive group, ∆ %SUVmax and ∆ %skewness were moderately useful for predicting pCR, and the respective AUCs were 0.747 and 0.758 (p = 0.033 and 0.026). Although there was no significant difference in the AUCs between groups for these parameters, an additional 3/22 patients in the HER2-positive group with pCR were identified when ∆ %skewness and ∆ %SUVmax were considered together (p = 0.031). The absolute values for each parameter before NAC and after 2 cycles cannot predict pCR in our patients. Neither ∆ %MTV nor ∆ %TLG was efficiently predictive of pCR in any group.The early changes in the textural features of 18F-FDG PET images after two cycles of NAC are predictive of pCR in both HER2-negative and HER2-positive patients; this evidence warrants confirmation by further research.
Keywords: Breast cancer; 18F-FDG PET; Neoadjuvant chemotherapy; Textural feature

Effect of resolution recovery using graph plots on regional cerebral blood flow in healthy volunteers by Nobuhiro Yada; Hideo Onishi; Masahiro Miyai; Kentarou Ozasa; Takashi Katsube; Keiichi Onoda; Masuo Haramoto; Yasushi Yamamoto; Shuhei Yamaguchi; Hajime Kitagaki (553-562).
We evaluated the effect of resolution recovery (RR) using graph plots on regional cerebral blood flow (rCBF) in brain perfusion single-photon emission computed tomography (SPECT) images derived from healthy volunteers and patients diagnosed with probable Alzheimer’s disease.We acquired brain perfusion SPECT images with scatter correction (SC), computed tomography-based attenuation correction (CTAC), and RR from a three-dimensional brain phantom and from healthy volunteers. We then compared contrast-to-noise ratio, count density ratios, increase maps, and rCBF using statistical parametric mapping 8.Regional brain counts were significantly increased from 20–24% with SC, CTAC, and RR compared with SC and CTAC. Mean CBF in healthy volunteers was 42.5 ± 5.4 mL/100 g/min. Average rCBF determined using SC, CTAC and RR increased 7.5, 2.0, and 3.7% at the thalamus, posterior cingulate, and whole brain, respectively, compared with SC and CTAC.Resolution recovery caused variations in normal rCBF because counts increased in cerebral regions.
Keywords: Brain perfusion; Single-photon emission computed tomography; Statistical parametric mapping (SPM); Computed tomography-based attenuation correction; Neurology

A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [18F]THK5351 and [11C]PIB by Miho Shidahara; Benjamin A. Thomas; Nobuyuki Okamura; Masanobu Ibaraki; Keisuke Matsubara; Senri Oyama; Yoichi Ishikawa; Shoichi Watanuki; Ren Iwata; Shozo Furumoto; Manabu Tashiro; Kazuhiko Yanai; Kohsuke Gonda; Hiroshi Watabe (563-569).
To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study.We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer’s disease (AD) PET studies of both [18F]THK5351 and [11C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data.In regions of high uptake of [18F]THK5351 and [11C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition.Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.
Keywords: Partial volume correction; Tau PET; Image processing; [18F]THK5351