Annals of Nuclear Medicine (v.31, #6)

Pathogenesis and FDG-PET/CT findings of Epstein–Barr virus-related lymphoid neoplasms by Akira Toriihara; Reiko Nakajima; Ayako Arai; Masashi Nakadate; Koichiro Abe; Kazunori Kubota; Ukihide Tateishi (425-436).
Epstein–Barr virus (EBV) is one of the most common viruses, infecting more than 90% of the adult population worldwide. EBV genome is detected in some lymphoid neoplasms. Not only their histopathological subtypes, but also their backgrounds and their clinical courses are variable. A number of B-cell lymphoproliferative disorders associated with the immunocompromised state are related to EBV infection. The incidences of these disorders have been increasing along with generalization of organ transplantations and use of immunosuppressive treatments. Furthermore, some EBV-positive lymphoma can also occur in immunocompetent patients. While evaluating patients with generalized lymphadenopathy of unknown cause by positron emission tomography/computed tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET/CT), the possibility of lymphoid neoplasms should be considered in some patients, and a careful review of the background and previous history of the patients is necessary. In this review article, we describe the pathogenesis of EBV-related lymphoid neoplasms and then present FDG-PET/CT images of representative diseases. In addition, we also present a review of other EBV-related diseases, such as infectious mononucleosis and nasopharyngeal carcinoma.
Keywords: Epstein–Barr virus; FDG-PET/CT; Lymphoproliferative diseases; Lymphoma

Pictorial review of 18F-FDG PET/CT findings in musculoskeletal lesions by Mana Ishibashi; Yoshio Tanabe; Shinya Fujii; Toshihide Ogawa (437-453).
We herein reviewed 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) findings in a number of musculoskeletal lesions including malignant tumors, benign tumors, and tumor-like lesions with correlations to other radiographic imaging modalities, and described the diversity of the 18F-FDG PET/CT findings of this entity. Malignant primary musculoskeletal tumors are typically 18F-FDG avid, whereas low-grade malignant tumors show mild uptake. Benign musculoskeletal tumors generally show a faint uptake of 18F-FDG, and tumor-like conditions also display various uptake patterns of 18F-FDG. Although musculoskeletal tumors show various uptakes of 18F-FDG on PET/CT, its addition to morphological imaging modalities such as CT and MRI is useful for the characterization and differentiation of musculoskeletal lesions.
Keywords: FDG; PET/CT; Bone tumor; Soft tissue tumor

IQ-SPECT for thallium-201 myocardial perfusion imaging: effect of normal databases on quantification by Takahiro Konishi; Kenichi Nakajima; Koichi Okuda; Hiroto Yoneyama; Shinro Matsuo; Takayuki Shibutani; Masahisa Onoguchi; Seigo Kinuya (454-461).
Although IQ-single-photon emission computed tomography (SPECT) provides rapid acquisition and attenuation-corrected images, the unique technology may create characteristic distribution different from the conventional imaging. This study aimed to compare the diagnostic performance of IQ-SPECT using Japanese normal databases (NDBs) with that of the conventional SPECT for thallium-201 (201Tl) myocardial perfusion imaging (MPI).A total of 36 patients underwent 1-day 201Tl adenosine stress–rest MPI. Images were acquired with IQ-SPECT at approximately one-quarter of the standard time of conventional SPECT. Projection data acquired with the IQ-SPECT system were reconstructed via an ordered subset conjugate gradient minimizer method with or without scatter and attenuation correction (SCAC). Projection data obtained using the conventional SPECT were reconstructed via a filtered back projection method without SCAC. The summed stress score (SSS) was calculated using NDBs created by the Japanese Society of Nuclear Medicine working group, and scores were compared between IQ-SPECT and conventional SPECT using the acquisition condition-matched NDBs. The diagnostic performance of the methods for the detection of coronary artery disease was also compared.SSSs were 6.6 ± 8.2 for the conventional SPECT, 6.6 ± 9.4 for IQ-SPECT without SCAC, and 6.5 ± 9.7 for IQ-SPECT with SCAC (p = n.s. for each comparison). The SSS showed a strong positive correlation between conventional SPECT and IQ-SPECT (r = 0.921 and p < 0.0001), and the correlation between IQ-SPECT with and without SCAC was also good (r = 0.907 and p < 0.0001). Regarding diagnostic performance, the sensitivity, specificity, and accuracy were 80.8, 78.9, and 79.4%, respectively, for the conventional SPECT; 80.8, 80.3, and 82.0%, respectively, for IQ-SPECT without SCAC; and 88.5, 86.8, and 87.3%, respectively, for IQ-SPECT with SCAC, respectively. The area under the curve obtained via receiver operating characteristic analysis were 0.77, 0.80, and 0.86 for conventional SPECT, IQ-SPECT without SCAC, and IQ-SPECT with SCAC, respectively (p = n.s. for each comparison).When appropriate NDBs were used, the diagnostic performance of 201Tl IQ-SPECT was comparable with that of the conventional system regardless of different characteristics of myocardial accumulation in the conventional system.
Keywords: IQ-SPECT; Japanese normal databases; Myocardial perfusion imaging; Rapid acquisition

Prognostic value of pre-treatment 18F-FDG-PET uptake in small-cell lung cancer by Meryem Aktan; Mehmet Koc; Gul Kanyilmaz; Berrin Benli Yavuz (462-468).
Small-cell lung cancer (SCLC) is an aggressive disease, despite an initially favorable response to treatment, and its prognosis is still poor. Multiple parameters have been studied as possible prognostic factors, but none of them are reliable enough to change the treatment approach. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a novel imaging technique for staging of SCLC. The aim of this study was to evaluate the prognostic value of pre-treatment FDG-PET parameters on clinical outcome in limited stage (LS) SCLC patients treated with curative thoracic radiotherapy (RT) and chemotherapy.Clinical records of 46 LS-SCLC patients with pre-treatment FDG-PET imaging were retrospectively reviewed. Patients were treated with definitive RT for a total dose of 50–60 Gy and chemotherapy. The clinical endpoints were progression-free survival (PFS) and overall survival (OS).The median age was 59 (range 30–82) years, and median follow-up time was 23.2 months (range 5–82.8 months). Median OS was 30.9 months for pre-treatment tumor maximum standardized uptake value (SUVmax) <9.3 and 20.6 months for SUVmax ≥9.3 (p = 0.027) and PFS was 55.6 months for SUVmax <9.3 and 38.6 months for SUVmax ≥9.3 (p = 0.16). Median OS was 73 months for pre-treatment lymph node SUVmax <5.8 and 21 months for ≥5.8 (p = 0.01) and PFS was 38.6 months (range 6.8–70.3 months) for SUVmax-LN ≥5.8; all patients with SUVmax-LN <5.8 were alive (p = 0.07). Median survival time was 28.2 months (range 21.7–34.7 months) for patients younger than 65 and 8.7 months (range 5.7–11.8 months) for those ≥65 years (p = 0.00).Pre-treatment FDG-PET uptake may be a valuable tool to evaluate prognosis in SCLC patients. Patients with a higher pre-treatment FDG uptake may be considered at increased risk of failure and may benefit from more aggressive treatment approaches.
Keywords: FDG-PET; Lung cancer; Small-cell lung cancer; Prognosis

Comparative evaluation of the algorithms for parametric mapping of the novel myocardial PET imaging agent 18F-FPTP by Ji Who Kim; Seongho Seo; Hyeon Sik Kim; Dong-Yeon Kim; Ho-Young Lee; Keon Wook Kang; Dong Soo Lee; Hee-Seung Bom; Jung-Joon Min; Jae Sung Lee (469-479).
(18F-fluoropentyl)triphenylphosphonium salt (18F-FPTP) is a new promising myocardial PET imaging tracer. It shows high accumulation in cardiomyocytes and rapid clearance from liver. We performed compartmental analysis of 18F-FPTP PET images in rat and evaluated two linear analyses: linear least-squares (LLS) and a basis function method (BFM) for generating parametric images. The minimum dynamic scan duration for kinetic analysis was also investigated and computer simulation undertaken. 18F-FPTP dynamic PET (18 min) and CT images were acquired from rats with myocardial infarction (MI) (n = 12). Regions of interest (ROIs) were on the left ventricle, normal myocardium, and MI region. Two-compartment (K 1 and k 2; 2C2P) and three-compartment (K 1k 3; 3C3P) models with irreversible uptake were compared for goodness-of-fit. Partial volume and spillover correction terms (V a and α = 1 − V a ) were also incorporated. LLS and BFM were applied to ROI- and voxel-based kinetic parameter estimations. Results were compared with the standard ROI-based nonlinear least-squares (NLS) results of the corresponding compartment model. A simulation explored statistical properties of the estimation methods.The 2C2P model was most suitable for describing 18F-FPTP kinetics. Average K 1, k 2, and V a values were, respectively, 6.8 (ml/min/g), 1.1 (min−1), and 0.44 in normal myocardium and 1.4 (ml/min/g), 1.1 (min−1), and 0.32, in MI tissue. Ten minutes of data was sufficient for the estimation. LLS and BFM estimations correlated well with NLS values for the ROI level (K 1: y = 1.06x + 0.13, r 2  = 0.96 and y = 1.13x + 0.08, r 2  = 0.97) and voxel level (K 1: y = 1.22x − 0.30, r 2  = 0.90 and y = 1.26x + 0.00, r 2  = 0.92). Regional distribution of kinetic parametric images (αK 1, K 1, k 2, V a) was physiologically relevant. LLS and BFM showed more robust characteristics than NLS in the simulation.Fast kinetics and highly specific uptake of 18F-FPTP by myocardium enabled quantitative analysis with the 2C2P model using only the initial 10 min of data. LLS and BFM were feasible for estimating voxel-wise parameters. These two methods will be useful for quantitative evaluation of 18F-FPTP distribution in myocardium and in further studies with different conditions, disease models, and species.
Keywords: Quantification; Parametric image; Simulation; Myocardial PET

Erratum to: Comparative evaluation of the algorithms for parametric mapping of the novel myocardial PET imaging agent 18F-FPTP by Ji Who Kim; Seongho Seo; Hyeon Sik Kim; Dong-Yeon Kim; Ho-Young Lee; Keon Wook Kang; Dong Soo Lee; Hee-Seung Bom; Jung-Joon Min; Jae Sung Lee (480-480).

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET by Tadashi Watabe; Kohei Hanaoka; Sadahiro Naka; Yasukazu Kanai; Hayato Ikeda; Masanao Aoki; Eku Shimosegawa; Mitsunori Kirihata; Jun Hatazawa (481-485).
The purpose of this study was to establish a practical method to estimate the absolute boron concentrations in the tissues based on the standardized uptake values (SUVs) after administration of 4-borono-phenylalanine (BPA) using 4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) PET.Rat xenograft models of C6 glioma (n = 7, body weight 241 ± 28.0 g) were used for the study. PET was performed 60 min after intravenous injection of 18F-FBPA (30.5 ± 0.7 MBq). After the PET scanning, BPA-fructose (167.3 ± 18.65 mg/kg) was administered by slow intravenous injection to the same subjects. The rats were killed 60 min after the BPA injection and tissue samples were collected from the major organs and tumors. The absolute boron concentrations (unit: ppm) in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The boron concentrations in the tissues/tumors were also estimated from the 18F-FBPA PET images using the following formula: estimated absolute boron concentration (ppm) = 0.0478 × [BPA dose (mg/kg)] × SUV. The measured absolute boron concentrations (mBC) by ICP-OES and the estimated boron concentrations (eBC) from the PET images were compared.The percent difference between the mBC and eBC calculated based on the SUVmax was −5.2 ± 21.1% for the blood, −9.4 ± 22.3% for the brain, 1.6 ± 21.3% for the liver, −14.3 ± 16.8% for the spleen, −9.5 ± 27.5% for the pancreas, and 3.4 ± 43.2% for the tumor. Relatively large underestimation was observed for the lung (−48.4 ± 16.2%), small intestine (−37.8 ± 19.3%) and large intestine (−33.9 ± 11.0%), due to the partial volume effect arising from the air or feces contained in these organs. In contrast, relatively large overestimation was observed for the kidney (34.3 ± 29.3%), due to the influence of the high uptake in urine.The absolute boron concentrations in tissues/tumors can be estimated from the SUVs on 18F-FBPA PET using a practical formula. Caution must be exercised in interpreting the estimated boron concentrations in the lung, small intestine and large intestine, to prevent the adverse effects of overexposure, which could occur due to underestimation by partial volume effect using PET.
Keywords: FBPA; Positron emission tomography; Boron concentration

Our study was designed to explore the utility of 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) for the detection of hepatocellular carcinoma (HCC) and specifically to compare the diagnostic performance of 99mTc-3PRGD2 integrin receptor imaging and 2-18-fluoro-2-deoxy-d-glucose (18F-FDG) metabolic imaging in a nude mouse model. 99mTc-3PRGD2 was synthesized using a HYNIC-3PRGD2 lyophilized kit with 99mTcO4 labelling. The nude mouse animal model was established by subcutaneously injecting 5 × 107/ml HepG2 cells into the shoulder flank of each mouse. Biodistribution studies were performed at 0.5, 1, 2 and 4 h after intravenous administration of 0.37 MBq of 99mTc-3PRGD2. Immunohistochemistry was performed to evaluate the expression level of integrin αvβ3 in the HCC tissues. Dynamic imaging was performed using list-mode after the administration of 55.5 MBq of 99mTc-3PRGD2, to reconstruct the multiphase images and acquire the best initial scan time. At 8, 12, 16, 20 and 24 days after inoculation with HepG2 cells, 55.5 MBq of 99mTc-3PRGD2 and 37 MBq of 18F-FDG were injected successively into the nude mouse model, subsequently, simultaneous SPECT/PET imaging was performed to calculate the tumour volume and tumour uptake of 99mTc-3PRGD2 and 18F-FDG.The biodistribution study first validated that the tumour uptake of 99mTc-3PRGD2 at the different time points was higher than that of all the other organs tested in the experiment, except for the kidney. Integrin αvβ3 expressed highly in early stage HCC and declined for further necrosis of the tumour tissue. Subcutaneous tumours were visualized clearly with excellent contrast under 99mTc-3PRGD2 SPECT/CT imaging, and the multiphase imaging comparison showed the tumours were prominent at 0.5 h, suggesting that the best initial scan time is 0.5 h post-injection. The comparison of the imaging results of the two methods showed that 99mTc-3PRGD2 integrin receptor imaging was more sensitive than 18F-FDG metabolic imaging for the detection of early stage HCC, meanwhile the tumour uptake of 99mTc-3PRGD2 was consistently higher than that of 18F-FDG. However, as tumour necrosis further increased in HCC tissues, the uptake of 18F-FDG was higher than that of 99mTc-3PRGD2.Our study demonstrated that 99mTc-3PRGD2 is a valuable tumour molecular probe for the detection of early stage HCC compared with 18F-FDG, meriting further investigation of 99mTc-3PRGD2 as a novel SPECT tracer for tumour imaging.
Keywords: 99mTc-3PRGD2 ; Hepatocellular carcinoma; Integrin αvβ3; 18F-FDG