Annals of Nuclear Medicine (v.22, #1)

PET kinetic analysis: error consideration of quantitative analysis in dynamic studies by Yoko Ikoma; Hiroshi Watabe; Miho Shidahara; Mika Naganawa; Yuichi Kimura (1-11).
Positron emission tomography dynamic studies have been performed to quantify several biomedical functions. In a quantitative analysis of these studies, kinetic parameters were estimated by mathematical methods, such as a nonlinear least-squares algorithm with compartmental model and graphical analysis. In this estimation, the uncertainty in the estimated kinetic parameters depends on the signal-to-noise ratio and quantitative analysis method. This review describes the reliability of parameter estimates for various analysis methods in reversible and irreversible models.
Keywords: PET; Compartmental model; Error analysis

Surveillance study for creating the national clinical database relating to ECG-gated myocardial perfusion SPECT of asymptomatic ischemic heart disease in patients with type-2 diabetes mellitus: J-ACCESS 2 study design by Hideo Kusuoka; Yoshimitsu Yamasaki; Tohru Izumi; Atsunori Kashiwagi; Ryuzo Kawamori; Kazuaki Shimamoto; Nobuhiro Yamada; Tsunehiko Nishimura (13-21).
Diabetes mellitus is an independent risk factor for acute myocardial infarction. Thus, a surveillance study was conducted as part of studies to create a national database related to electrocardiogram (ECG)-gated myocardial perfusion single-photon emission computed tomography (SPECT) of ischemic heart disease.Single-photon emission computed tomography was conducted in patients with type 2 diabetes mellitus and their prognoses will be followed for 3 years, stratified by patients’ clinical background and SPECT findings.A total of 513 patients from 50 institutions were enrolled in this study, 297 of whom were men (age 66.2 ± 0.4 years, mean ± SEM) and 261 women (age 67.8 ± 0.5 years). They have a history of retinopathy (25.3%), neuropathy (19.9%), cerebrovascular disorder, chronic obstructive pulmonary disease, and photocoagulation. Major risk factors for present disease were hypertension (82.3%) and hyperlipidemia (79.7%). In 244 patients (129 men and 115 women), body mass index (BMI) was 25 or more. Fifty-two of them (10.1%) underwent coronary angiography; of these, 26 (50.0%) had no coronary artery lesions with 75% or more stenosis, and only 1 (1.9%) had a left main trunk with 50% or more stenosis. An overwhelming majority of patients (94.3%) underwent SPECT imaging by a 1-day stress-followed-by-rest procedure. Stress procedure was exercise in most (70.8%) patients, followed by dipyridamole infusion in 14.6%, adenosine infusion in 6.6%, and adenosine triphosphate infusion in 5.7%. Endpoint of stress examination was most often fatigue in lower limbs (40.7%), followed by completion of pharmacological stress protocol (28.7%), and achievement of target heart rate (26.3%). The largest number of patients (198, 38.6%) received 99mTc-tetrofosmin at an initial dosage of 200–300 MBq (mean 331 ± 3 MBq) followed by a second dosage of 700–800 MBq (mean 748 ± 8 MBq). Among them, 491 (95.7%) received some kind of therapeutic drug: hypoglycemic drugs were used by the largest number (83.2%), followed by hypotensive (66.7%), hypolipidemic (40.7%), and antiplatelet drugs (27.7%), vasodilators (5.5%), and antioxidants and others (2.3%).This study was designed to clarify the correlation between coronary artery disease and diabetes mellitus as its risk factor based on the clinical and imaging findings. Patient enrollment was closed on September 30, 2005, and follow-up is now under way.
Keywords: Diabetes mellitus; Ischemic heart disease; ECG-gated myocardial perfusion SPECT; 99mTc-tetrofosmin; Prognosis prediction

Does partial volume corrected maximum SUV based on count recovery coefficient in 3D-PET/CT correlate with clinical aggressiveness of non-Hodgkin’s lymphoma? by Tetsuya Tsujikawa; Hideki Otsuka; Naomi Morita; Hiroshi Saegusa; Masato Kobayashi; Hidehiko Okazawa; Hiromu Nishitani (23-30).
There is much controversy about the correlation between the degree of 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake and clinical aggressiveness of non-Hodgkin’s lymphoma (NHL). In this study, we investigated whether partial volume corrected FDG uptake based on count recovery coefficient in 3D-positron emission tomography (PET)/computed tomography (CT) correlates with the clinical aggressiveness of NHL and improves diagnostic accuracy.Forty-two patients with NHL underwent FDG-PET/CT scans (26 aggressive NHLs and 16 indolent ones). Count recovery curve was obtained using NEMA 2001 body phantom. Scan protocol and reconstructive parameters in the phantom study were the same as those in a clinical scan except for emission time. Relative recovery coefficient (RC) was calculated as RC = A/B (A, maximum pixel count of each hot sphere; B, maximum pixel count of greatest sphere). Partial volume corrected maximum count of standardized uptake value (PVC-SUV) was calculated as PVC-SUV = NC-SUV/RC (NC-SUV: non-corrected maximum count of SUV). Three parameters (NC-SUV, PVC-SUV, and size) between aggressive and indolent NHLs were compared.Significant differences were shown in all parameters between aggressive and indolent NHLs. Means ± SD of NC-SUV, PVC-SUV, and size was as following: NC-SUV (15.3 ± 6.9, 8.7 ± 7.0; P < 0.01), PVC-SUV (18.2 ± 8.1, 12.7 ± 7.8; P < 0.05), and size (mm, 32.4 ± 18.3, 21.9 ± 10.3; P < 0.05). When an NC-SUV of 9.5 was the cutoff for aggressive NHL, the receiver-operating-characteristic (ROC) analysis correctly identified 21 of 26 aggressive ones. Sensitivity and specificity were 81% each, and the positive and negative predictive values were 88% and 72%, respectively. When a PVCSUV of 11.2 was the cutoff, the ROC analysis revealed 81% sensitivity, 63% specificity, and positive and negative predictive values of 78% and 67%, respectively. At a cutoff for aggressive NHL of a size of 27 mm, the ROC analysis revealed 50% sensitivity, 81% specificity, and positive and negative predictive values of 81% and 50%, respectively. The comparison of area under the curve in ROC analyses indicated that NC-SUV showed the greatest diagnostic accuracy (NC-SUV 0.84, PVC-SUV 0.72, and size 0.69).Diagnostic accuracy of PVC-SUV was inferior to that of NC-SUV. These results suggest that NC-SUV, which contains information on both size and FDG density, provides better differentiation between aggressive and indolent NHLs than PVC-SUV.
Keywords: Non-Hodgkin’s lymphoma; Clinical aggressiveness; 3D-PET/CT; Count recovery; Partial volume corrected SUV

Staging of bronchiolitis obliterans syndrome (BOS) following lung transplantation is based on declines in forced expiratory volume in 1 s (FEV1). The aim of this study was to evaluate the usefulness of 133Xe ventilation scintigraphy in the early detection of BOS following living-donor lobar lung transplantation (LDLLT), to compare 133Xe washout imaging with computed tomography (CT) findings for early detection of BOS following LDLLT, and to evaluate 133Xe washout imaging by quantitative analyses.Subjects comprised 30 double-lung recipients and 1 single-lung recipient, who had undergone LDLLT at our institution and survived more than 1 year. Clinically diagnosed BOS developed in six recipients. Declines in graft function were evaluated using a combination of three methods, namely, dynamic spirometry, high-resolution CT (HRCT), and 133Xe ventilation scintigraphy. Findings for all transplanted lungs were compared between CT and 133Xe washout imaging. 133Xe washout imaging was assessed using mean transit time (MTT) of bi-and unilateral lungs. Correlations between MTT of bilateral lungs and FEV1% were evaluated. Differences in MTT between BOS and non-BOS lungs, and between non-BOS and donor lungs were also evaluated on unilateral lungs. Appropriate cut-off values of MTT of unilateral lungs were set for the diagnosis of BOS.In all six BOS cases, prolonged-washout images of engrafted lungs revealed early-phase BOS with declines from baseline FEV1, whereas only one BOS case could be detected using early CT findings of BO (bronchodilatation, decrease in number and size of pulmonary vessels, thickening of septal lines, and volume reduction). A significant correlation was identified between MTT and FEV1% (r = −0.346, P < 0.0001). MTT of unilateral lungs was significantly longer in BOS lungs than in non-BOS lungs (P < 0.0001). The cut-off MTT of unilateral lungs for the diagnosis of BOS was set at 64.77 s.Our data show that 133Xe washout imaging offers excellent potential for early detection of BOS compared with early CT findings. Using 133Xe washout imaging and MTT with radioactive tracer offers a noninvasive indication of selective ventilatory function in engrafted lungs following LDLLT. MTT appears useful for identifying BOS following LDLLT and allows quantitative evaluation of graft function in unilateral lungs.
Keywords: Bronchiolitis obliterans syndrome (BOS); Living-donor lobar lung transplantation (LDLLT); 133Xe scintigraphy; Mean transit time (MTT); Prolonged-washout images

Diagnosis supporting algorithm for lymph node metastases from colorectal carcinoma on 18F-FDG PET/CT by Kazumasa Inoue; Takashi Sato; Hideaki Kitamura; Masaaki Ito; Yoshiyuki Tsunoda; Akira Hirayama; Hideo Kurosawa; Takashi Tanaka; Masahiro Fukushi; Noriyuki Moriyama; Hirofumi Fujii (41-48).
We studied the improvement of the detect-ability of lymph node (LN) metastases from colorectal cancer in 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) by analyzing the acquired counts with a statistical method.Thirty-nine metastatic LNs from 32 cases with colorectal cancer were included in this study. “Uptake region” was defined as the site where counts were higher than the average plus 3 standard deviations (SDs) on each transaxial image of FDG PET. After the initial uptake regions were selected, these high accumulation areas were automatically excluded from consideration thereafter. This method was repeated and new uptake regions were identified. This method was repeated up to five times. After that, the stacked-up uptake regions were compared with computed tomography (CT) images, and the high accumulation areas that were superimposed on the normal structures, such as intestine, vessels, and ureters, were excluded from the consideration. The remaining uptake regions were diagnosed as metastatic LNs, and the detectability of LN metastases was calculated. We then compared these statistical results with the results obtained on the basis of visual assessments by radiologists.Our proposed method showed the best results when the procedures were repeated three times in the light of detectability. After being repeated three times, this method detected 15/23 (65.2%) metastatic LNs in the first LN group, 16/16 (100%) in the second-third LN groups and 31/39 (79.4%) in the total LNs, whereas the radiologists diagnosed 8/23 (34.8%) of metastatic first LNs, 12/16 (75.0%) in the second-third LNs and 20/39 (51.3%) in the total LNs. A statistically significant difference was observed between the result of iteration number 3 and that by radiologists as for the second—third LNs and the total LNs.This study suggests that our proposed statistical method could improve the detectability of LN metastases from colorectal cancer. Our method will help radiologists to detect small metastatic lesions such as LN metastases.
Keywords: PET; FDG; Lymph node; Colorectal cancer; Diagnosis supporting system

The occurrence of multidrug resistance (MDR) is a major cause of resistance to chemotherapeutic agents in patients with lung cancer, in part owing to the overexpression of MDR-related proteins. Technetium-99m-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) has been shown to be a substrate for some MDR-related proteins. The aim of this study is to evaluate the role of 99mTc-MIBI scintigraphy for functional imaging of MDR-related protein phenotypes.To determine the correlation between 99mTc-MIBI scintigraphy and the expression level of P-glycoprotein (Pgp), multidrug-resistance protein (MRP), and glutathione-S-transferase Pi (GSTπ), 26 patients (17 men and 9 women, median age 57.5 years) with primary lung cancer were investigated. Following intravenous administration of 925 MBq 99mTc-MIBI, single-photon emission computed tomography (SPECT) and computed tomography (CT) were performed at 15 min and 2 h. On the basis of the fused images, tumor to background (T/B) ratio of both early and delayed images, and washout rate (WR%) of 99mTc-MIBI were calculated. The immunohistochemical staining of Pgp, MRP, and GSTπ was performed, and the expression level was semiquantitated using a pathoimage analysis system. The imaging results were compared with the status of Pgp, MRP, and GSTπ expression.The WR% of 99mTc-MIBI showed a significant positive correlation with Pgp expression (r = 0.560, P = 0.003), as no correlation was observed between WR% and MRP or GSTπ (r = 0.354, P = 0.076; r = 0.324, P = 0.106). Neither early T/B nor delayed T/B correlated with the expression level of Pgp, MRP, and GSTπ. WR%, Pgp, and GSTπ expression showed significant differences between squamous cell carcinoma (group A) and adenocarcinoma (group B). There was no significant difference among Pgp, MRP, and GSTπ expression levels in any cases (P > 0.05).Our data confirmed that 99mTc-MIBI scintigraphy is useful for determining the MDR caused by Pgp in patients with primary lung cancer.
Keywords: Technetium-99m-hexakis-2-methoxyisobutylisonitrile; Multidrug-resistance-related protein; Primary lung cancer; Multidrug resistance

The objective of this study was to evaluate whether the radioactivity of tumor tissues inoculated into mice can be monitored quantitatively with a planar positron imaging system (PPIS). 18F-fluoro-d-glucose, 18F-fluorothymidine, or d-18F-fluoromethyl tyrosine were intravenously administered into HeLa-bearing mice. In vivo uptake of each labeled compound in tumors was monitored with the PPIS, followed by the measurement of radioactivity in tumor tissue using tissue dissection analysis. The standardized uptake values (SUVs) in PPIS measurement and ex vivo tissue dissection analysis were derived using the tumor volume and tumor weight, respectively.Radioactivities of tumors in mice obtained via PPIS imaging correlated significantly with those by tissue dissection analysis. The SUV derived by the PPIS data and the estimated tumor volume correlated roughly with those by ex vivo tissue dissection analysis.The results of our experiment indicate the feasibility of noninvasive, quantitative tumor monitoring in mouse/rat studies with the PPIS.
Keywords: Planar positron imaging system; Noninvasive monitoring; Tumor; Mouse

Fluorine-18-labeled 5-fluorouracil is a useful radiotracer for differentiation of malignant tumors from inflammatory lesions by Sadatoshi Sugae; Akiko Suzuki; Nobukazu Takahashi; Ryogo Minamimoto; Chao Cheng; Chumpol Theeraladanon; Itaru Endo; Shinji Togo; Tomio Inoue; Hiroshi Shimada (65-72).
[18F]-2-fluoro-2-deoxy-d-glucose ([18F]-FDG) is a useful radiotracer to detect malignant tumors. However, inflammatory processes are likely to be mistaken as malignant tumors owing to strong accumulation of [18F]-FDG. The fluorinated nucleoside base 5-fluorouracil has remained an important antimetabolite agent in the treatment of a variety of cancers. The objective of this study was to evaluate the possibility of discriminating between malignant tumors and inflammation by [18F]-5-fluorouracil ([18F]-5-FU).[18F]-5-FU was made with >95% radiochemical purity in our laboratory. BALB/cAJcl-nu/nu mice were subcutaneously inoculated with colon carcinoma cell line, colon 26, into the left side of the back and turpentine oil into the right side of the back to cause chemical inflammation. We examined the biodistribution of [18F]-5-FU in control mice and tumor-inflammation mice. We also examined the biodistribution of [18F]-FDG as a baseline study. Approximately 1 MBq of either [18F]-5-FU or [18F]-FDG was injected into the tail vein of each mouse. The biodistribution study was performed at 1 and 2 h after injection. The radioactivity of each organ was measured by a gamma counter.[18F]-5-FU uptakes in the liver and the kidney were especially high. Tumor-to-blood ratios were significantly higher at 2 h than at 1 h (3.69 ± 0.40 vs. 1.81 ± 0.37, P < 0.001). Tumor-to-inflammation ratios at 2 h following injection were significantly higher than those at 1 h (1.94 ± 0.44 vs. 1.26 ± 0.20, P < 0.001). At 2 h after radiotracer injection, the tumor-to-inflammation ratio of [18F]-5-FU was significantly higher than that of [18F]-FDG (1.94 ± 0.44 vs. 1.03 ± 0.23, P = 0.001).Our data suggest that [18F]-5-FU has a diagnostic potential as a positron emission tomography ligand for differentiating malignant tumors from inflammatory lesions.
Keywords: [18F]-5-FU; Tumor; Inflammation; Mouse model; PET

Distinctive FDG and FES accumulation pattern of two tamoxifen-treated patients with endometrial hyperplasia by Tetsuya Tsujikawa; Hidehiko Okazawa; Yoshio Yoshida; Tetsuya Mori; Masato Kobayashi; Tatsuro Tsuchida; Yasuhisa Fujibayashi (73-77).
16α-[18F]Fluoro-17β-estradiol (FES) is an estrogen receptor (ER) ligand used for the detection of ER-positive malignant tumors such as breast cancer. We recently reported the feasibility of combined FES-and 2-[18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) scans for the differential diagnosis of endometrial tumors. ER expression measured by FES-PET was preserved in endometrial hyperplasia, whereas ERs were assumed to be reduced in endometrial carcinoma with accelerated glucose metabolism measured by FDG-PET. We report two postmenopausal patients under suspicion of endometrial carcinoma on the basis of cytology and/or magnetic resonance imaging (MRI), who were on tamoxifen treatment since undergoing surgery for breast cancer. Pelvic MRI suggested endometrial carcinomas, whereas FDG-and FES-PET showed no abnormal tracer accumulation. A postoperative histopathologic examination revealed that the lesions were endometrial hyperplasias with no malignant findings. FES-PET enables us to evaluate the ERα expression of endometrium noninvasively, whereas the evaluation of ER expression using FES-PET requires careful attention regarding the influence of hormonal therapy because tamoxifen greatly affects FES accumulation of even endometrial hyperplasia, which should be an FES-avid lesion.
Keywords: Endometrial hyperplasia; Estrogen receptor; FES-PET; FDG-PET; Tamoxifen

A 64-year-old woman presented with a painless breast mass. Tc-99m methoxyisobutylisonitrile scintigraphy of both breasts showed a local area of abnormal uptake in the left breast in 5 min and 2 h. A skeletal scan showed very intense concentration of activity in the primary breast tumor in the left breast. A left mastectomy and an axillary dissection were performed. The predominant histologic type of the mass was an osteosarcoma, and the diagnosis of a primary osteogenic sarcoma of the breast was made. Primary osteogenic sarcoma of the breast is rare and represents less than 1% of all primary breast malignancies.
Keywords: Tc-99m MDP; Tc-99m MIBI; Osteogenic sarcoma of breast

Clinicopathological presentation of varying 18F-FDG uptake and expression of glucose transporter 1 and hexokinase II in cases of hepatocellular carcinoma and cholangiocellular carcinoma by Bishnuhari Paudyal; Noboru Oriuchi; Pramila Paudyal; Yoshito Tsushima; Tetsuya Higuchi; Mitsuyuki Miyakubo; Tomohiro Ishikita; Takashi Nakajima; Keigo Endo (83-86).
We report the results of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) and immunohistochemical staining of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in patients with hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) to observe the variation in 18F-FDG uptake and variation in expression of Glut-1 and HK-II in these hepatic tumors. In the case of HCC, moderate 18F-FDG uptake and strong expression of HK-II were detected, whereas Glut-1 was not expressed. Conversely, CCC showed high 18F-FDG uptake and increased expression of Glut-1 but HK-II was not expressed. The variation in the 18F-FDG uptake and expression of Glut 1 and HK-II in HCC and CCC might be owing to the difference in origin and the different mechanisms involved in glucose uptake, rate of glucose transporters, and hexokinase activity involved in the glycolytic pathway.
Keywords: 18F-FDG PET; Glucose transporter 1; Hexokinase II; Hepatocellular carcinoma; Cholangiocellular carcinoma

Idiopathic retroperitoneal fibrosis is an uncommon disease characterized by periaortic inflammation with gradual fibrosis and distortion of retroperitoneal structures such as the ureter. Several earlier case reports have documented hypermetabolic retroperitoneal activity on fluorodeoxyglucose positron emission tomography (FDG PET) in patients with active disease, and a decrease in the activity following immunosuppressive therapy. We report FDG PET positive findings in three patients presenting with active retroperitoneal fibrosis. In two cases, enhancing periaortic soft tissue seen on computed tomography (CT) markedly diminished following immunosuppressive therapy. In one patient, repeat FDG PET was performed following immunosuppressive therapy, with complete resolution of the retroperitoneal FDG avidity. We suggest that FDG PET may play a useful adjunct to anatomic imaging and serum inflammatory markers in assessing the severity of inflammation in retroperitoneal fibrosis, and in assessing the likelihood of response to immunosuppressive therapy. FDG PET may also be used in follow-up to assess therapeutic response if CT findings are unclear.
Keywords: PET; Retroperitoneal fibrosis; Ormond’s disease