Annals of Nuclear Medicine (v.28, #4)

18F-FDG-PET/CT in assessing response to neoadjuvant chemoradiotherapy for potentially resectable locally advanced esophageal cancer by Ur Metser; Farid Rashidi; Hadas Moshonov; Rebecca Wong; Jennifer Knox; Maha Guindi; Gail Darling (295-303).
To correlate metabolic response to neoadjuvant chemoradiotherapy (NACR) on FDG-PET/CT using PERCIST-based criteria to pathologic and clinical response, and survival in patients with locally advanced esophageal cancer (LAEC). Forty-five patients with LAEC underwent PET/CT at baseline and after NACR. Tumors were evaluated using PERCIST (PET response criteria in solid tumors)-based criteria including SUL, SUL tumor/liver ratio, % change in SUL. These parameters were compared to pathology regression grade (PRG), clinical response (including residual or new disease beyond the surgical specimen), and overall survival.On surgical pathology, there was complete or near-complete regression of tumor in 51.1 %, partial response in 42.2 %, and lack regression in 4.4 %. One patient (2.2 %) had progression of disease on imaging and did not undergo surgical resection. None of the baseline PET parameters had significant correlation to pathology regression grade or clinical response. On follow-up, a positive correlation was found between post-therapy SUL ratio, %∆ SUL and %∆ SUL ratio and clinical response (p = 0.025, 0.035, 0.030, respectively). A weak correlation was found between post-therapy SUL ratio to PRG (p = 0.049). A strong correlation was found between the metabolic response score and PRG (p = 0.002) as well as between metabolic response and clinical response (p < 0.001).PERCIST-based metabolic response assessment to NACR in LAEC may correlate with clinical outcome and survival.
Keywords: FDG; Esophageal cancer; PET; Neoadjuvant; Response assessment

18F-FDG PET as a single imaging modality in pediatric neuroblastoma: comparison with abdomen CT and bone scintigraphy by Yun Jung Choi; Hee Sung Hwang; Hyun Jeong Kim; Yong Hyu Jeong; Arthur Cho; Jae Hoon Lee; Mijin Yun; Jong Doo Lee; Won Jun Kang (304-313).
The purpose of this study was to evaluate the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) as a single imaging agent in neuroblastoma in comparison with other imaging modalities.A total of 30 patients with pathologically proven neuroblastoma who underwent FDG PET for staging were enrolled. Diagnostic performance of FDG PET and abdomen CT was compared in detecting soft tissue lesions. FDG PET and bone scintigraphy (BS) were compared in bone metastases. Maximal standardized uptake value (SUVmax) of primary or recurrent lesions was calculated for quantitative analysis.Tumor FDG uptake was detected in 29 of 30 patients with primary neuroblastoma. On initial FDG PET, SUVmax of primary lesions were lower in early stage (I–II) than in late stage (III–IV) (3.03 vs. 5.45, respectively, p = 0.019). FDG PET was superior to CT scan in detecting distant lymph nodes (23 vs. 18 from 23 lymph nodes). FDG PET showed higher accuracy to identify bone metastases than BS both on patient-based analyses (100 vs. 94.4 % in sensitivity, 100 vs. 77.8 % in specificity), and on lesion-based analyses (FDG PET: 203 lesions, BS: 86 lesions). Sensitivity and specificity of FDG PET to detect recurrence were 87.5 % and 93.8, respectively.FDG PET was superior to CT in detecting distant LN metastasis and to BS in detecting skeletal metastasis in neuroblastoma. BS might be eliminated in the evaluation of neuroblastoma when FDG PET is performed.
Keywords: Neuroblastoma; 18F-fluoro-2-deoxy-d-glucose positron emission tomography (18F-FDG PET); Bone metastasis; Bone scintigraphy

First experience with early dynamic 18F-NaF-PET/CT in patients with chronic osteomyelitis by Martin Freesmeyer; Franz F. Stecker; Jan-Henning Schierz; Gunther O. Hofmann; Thomas Winkens (314-321).
This study investigates whether early dynamic positron emission tomography/computed tomography (edPET/CT) using 18F-sodium fluoride-(18F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM).A total of 12 ed18F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late 18F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUVmax, edSUVmean, respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones.Starting in the 31–45 s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late 18F-NaF-PET/CT.This pilot study suggests that, in patients with COM, ed18F-NaF -PET offers additional information about early radiotracer distribution to standard 18F-NaF -PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed18F-NaF-PET to a three-phase bone scan.
Keywords: Positron emission tomography/computed tomography; Early dynamic positron emission tomography; 18F-sodium fluoride; 18F-NaF; Chronic osteomyelitis; List mode

The purpose of this study was to evaluate the lesion frequency and incremental added benefit with “true whole-body” 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of distal lower extremities. We compared this field of view with the typical whole-body view, from head to upper thighs, in numerous patients with known or suspected malignancy.True whole-body 18F-FDG PET/CT, from the top of the head to the bottom of the feet, was performed on 4574 consecutively registered patients with known or suspected malignancy. Using a variable sampling method, the PET images of head and torso were acquired for 90 s per bed position, and the images of lower extremities were acquired for 30 s per position, thus requiring between 22 and 24 min of emission scanning per patient. A log was maintained to record cases of abnormal findings in distal lower extremities outside the typical whole-body field of view. Suspected malignant lesions in distal lower extremities were verified by correlation with pathological findings and clinical follow-up.Abnormal findings in distal lower extremities were found in 647 (14.1 %; 95 % CI 13.1–15.2 %) of 4574 examinations. Increased FDG uptake was found in 559 examinations (12.2 %; 95 % CI 11.3–13.2 %). Lesions appeared malignant or equivocal in 67 examinations (1.5 %; 95 % CI 1.1–1.8 %) on the PET images. In 42 (0.9 %; 95 % CI 0.6–1.2 %) of 4574 examinations, these lesions were pathologically or clinically proven to be malignant. Detection of these malignancies resulted in changing clinical management in 21 (50 %) of 42 examinations. Definitive benign lesions were found in 492 examinations (10.7 %; 95 % CI 9.9–11.7 %) on the PET images. Abnormal findings were noted in 90 examinations (2.0 %; 95 % CI 1.6–2.4 %) consisting of 88 benign and 2 malignancies on the CT images alone.True whole-body 18F-FDG PET/CT was not of high yield and appears to offer little additional benefit, as to detection of additional metastases and involvement, but it may affect clinical management in patients with known or suspected malignancy.
Keywords: 18F-FDG; PET/CT; True whole-body imaging; Cancer imaging

Investigation of computer-aided diagnosis system for bone scans: a retrospective analysis in 406 patients by Osamu Tokuda; Yuko Harada; Yona Ohishi; Naofumi Matsunaga; Lars Edenbrandt (329-339).
The aim of this study was to investigate the diagnostic ability of a completely automated computer-assisted diagnosis (CAD) system to detect metastases in bone scans by two patterns: one was per region, and the other was per patient.This study included 406 patients with suspected metastatic bone tumors who underwent whole-body bone scans that were analyzed by the automated CAD system. The patients were divided into four groups: a group with prostatic cancer (N = 71), breast cancer (N = 109), males with other cancers (N = 153), and females with other cancers (N = 73). We investigated the bone scan index and artificial neural network (ANN), which are parameters that can be used to classify bone scans to determine whether there are metastases. The sensitivities, specificities, positive predictive value (PPV), negative predictive value (NPV), and accuracies for the four groups were compared. Receiver operating characteristic (ROC) analyses of region-based ANN were performed to compare the diagnostic performance of the automated CAD system.There were no significant differences in the sensitivity, specificity, or NPV between the four groups. The PPVs of the group with prostatic cancer (51.0 %) were significantly higher than those of the other groups (P < 0.01). The accuracy of the group with prostatic cancer (81.5 %) was significantly higher than that of the group with breast cancer (68.6 %) and the females with other cancers (65.9 %) (P < 0.01). For the evaluation of the ROC analysis of region-based ANN, the highest Az values for the groups with prostatic cancer, breast cancer, males with other cancers, and females with other cancers were 0.82 (ANN = 0.4, 0.5, 0.6, 0.7, and 0.8), 0.83 (ANN = 0.7), 0.81 (ANN = 0.5), and 0.81 (ANN = 0.6), respectively.The special CAD system “BONENAVI” trained with a Japanese database appears to have significant potential in assisting physicians in their clinical routine. However, an improved CAD system depending on the primary lesion of the cancer is required to decrease the proportion of false-positive findings.
Keywords: Bone scan; Computer-assisted diagnosis; Prostatic cancer; Breast cancer; Bone metastases

Performance measurement of PSF modeling reconstruction (True X) on Siemens Biograph TruePoint TrueV PET/CT by Young Sub Lee; Jin Su Kim; Kyeong Min Kim; Joo Hyun Kang; Sang Moo Lim; Hee-Joung Kim (340-348).
The Siemens Biograph TruePoint TrueV (B-TPTV) positron emission tomography (PET) scanner performs 3D PET reconstruction using a system matrix with point spread function (PSF) modeling (called the True X reconstruction). PET resolution was dramatically improved with the True X method. In this study, we assessed the spatial resolution and image quality on a B-TPTV PET scanner. In addition, we assessed the feasibility of animal imaging with a B-TPTV PET and compared it with a microPET R4 scanner.Spatial resolution was measured at center and at 8 cm offset from the center in transverse plane with warm background activity. True X, ordered subset expectation maximization (OSEM) without PSF modeling, and filtered back-projection (FBP) reconstruction methods were used. Percent contrast (% contrast) and percent background variability (% BV) were assessed according to NEMA NU2-2007. The recovery coefficient (RC), non-uniformity, spill-over ratio (SOR), and PET imaging of the Micro Deluxe Phantom were assessed to compare image quality of B-TPTV PET with that of the microPET R4.When True X reconstruction was used, spatial resolution was <3.65 mm with warm background activity. % contrast and % BV with True X reconstruction were higher than those with the OSEM reconstruction algorithm without PSF modeling. In addition, the RC with True X reconstruction was higher than that with the FBP method and the OSEM without PSF modeling method on the microPET R4. The non-uniformity with True X reconstruction was higher than that with FBP and OSEM without PSF modeling on microPET R4. SOR with True X reconstruction was better than that with FBP or OSEM without PSF modeling on the microPET R4.This study assessed the performance of the True X reconstruction. Spatial resolution with True X reconstruction was improved by 45 % and its % contrast was significantly improved compared to those with the conventional OSEM without PSF modeling reconstruction algorithm. The noise level was higher than that with the other reconstruction algorithm. Therefore, True X reconstruction should be used with caution when quantifying PET data.
Keywords: Performance measurement; PET

The study aimed to investigate the incidence of bone uptake of tracer on Tc-99m MIBI imaging and explore its influencing factors and significance for diagnosis of metabolic bone disease (MBD) in patients with hyperparathyroidism (HPT).Seventy-nine consecutive patients with histopathologically confirmed HPT (63 primary and 16 secondary) who had preoperative Tc-99m MIBI imaging were retrospectively evaluated. Serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured for all patients, and serum alkaline phosphatase (ALP) was measured for 62 patients. Of the 79 patients, 50 underwent bone mineral density (BMD) examination and 30 underwent bone scintigraphy. The incidence and characteristics of abnormal bone uptake of MIBI were recorded. Mann–Whitney test was performed to determine if serum iPTH, Ca, P, ALP, and BMD were different between the patients with and without MIBI bone uptake. Logistic regression analysis was used to analyze the factors that influence the bone uptake of MIBI. The concordance rate between Tc-99m MIBI imaging and bone scintigraphy in delineating MBD was calculated.Tc-99m MIBI imaging disclosed the abnormal bone uptake of tracer in 22 (27.8 %) patients. Of them, 19 showed diffusely increased activity in skeleton, 2 showed focal uptake in brown tumors, and one showed both above patterns. Patients with bone uptake MIBI had higher level of serum iPTH (Z = −4.34, P < 0.001) and ALP (Z = −3.50, P < 0.001) than those without bone uptake. Logistic regression analysis also showed that bone uptake of MIBI was correlated with serum iPTH (OR = 4.42, P < 0.001) and ALP (OR = 3.21, P = 0.002). Among the 30 patients that underwent bone scintigraphy, 76.7 % patients showed signs of MBD, and the concordance rate between Tc-99m MIBI imaging and bone scintigraphy was 60 % for detecting MBD.Bone uptake of MIBI in patients with HPT is commonly related to a high level of iPTH and ALP; it probably reflects an active stage of MBD, and it should be monitored during the conventional Tc-99m MIBI scintigraphy.
Keywords: Radionuclide imaging; Hyperparathyroidism; Skeleton; Metabolic bone disease

Prognostic value of 18F-fluorodeoxyglucose uptake before treatment for pharyngeal cancer by Hidenori Suzuki; Katsuhiko Kato; Yasushi Fujimoto; Yoshiyuki Itoh; Mariko Hiramatsu; Shinji Naganawa; Yasuhisa Hasegawa; Tsutomu Nakashima (356-362).
The purpose of this study was to evaluate an association found between overall survival of patients with pharyngeal squamous cell carcinoma (SCC) and pretreatment [18F]-2-fluorodeoxyglucose (18F-FDG) uptake, which are assessed by positron emission tomography combined with computed tomography (PET/CT). Next, we asked whether 18F-FDG uptake is correlated with overall survival in patients with pharyngeal SCC who underwent radical treatments such as surgery and radiotherapy in the multivariate analysis with adjustments for the clinical stage, primary site and treatment group.Forty-nine patients who were newly diagnosed as resectable pharyngeal SCC underwent pretreatment 18F-FDG-PET/CT. We used the maximum standardized uptake value (SUVmax) as 18F-FDG uptake. Overall survival rate was calculated by the Kaplan–Meier method. Univariate survival analysis was analyzed by log-rank test, and multivariate survival analysis was performed by a Cox proportional hazards model.Patients with SUVmax of the primary site ≥8 significantly exhibited shorter overall survival in univariate analysis (p < 0.04). Moreover, SUVmax of the primary site ≥8 was a significant prognostic factor in the multivariate analysis (p < 0.03).These results suggested that SUVmax of the primary site obtained by pretreatment 18F-FDG-PET/CT assessment is an important prognostic factor in patients with pharyngeal SCC.
Keywords: 18F-FDG-PET/CT; Pharyngeal squamous cell carcinoma; SUVmax; Overall survival

This study investigates modulation transfer function (MTF) in parallel beam (PB) and fan beam (FB) collimators using the Monte Carlo method with full width at half maximum (FWHM), square and circular-shaped holes, and scatter and penetration (S + P) components.A regulation similar to the lead-to-air ratio was used for both collimators to estimate output data. The hole pattern was designed to compare FB by PB parameters. The radioactive source in air and in a water phantom placed in front of the collimators was simulated using MCNP5 code.The test results indicated that the square holes in PB (PBs) had better FWHM than did the cylindrical (PBc) holes. In contrast, the cylindrical holes in the FB (FBc) had better FWHM than the square holes. In general, the resolution of FBc was better than that of the PBc in air and scatter mediums. The S + P decreased for all collimators as the distance from the source to the collimator surface (z) increased. The FBc had a lower S + P than FBs, but PBc had a higher S + P than PBs. Of the FB and PB collimators with the identical hole shapes, PBs had a smaller S + P than FBs, and FBc had a smaller S + P than PBc. The MTF value for the FB was greater than for the PB and had increased spatial frequency; the FBc had higher MTF than the FBs and PB collimators.Estimating the FB using PB parameters and diverse hole shapes may be useful in collimator design to improve the resolution and efficiency of SPECT images.
Keywords: Collimator; Hole shape; FWHM; Penetration; MTF

Assessment of [18F]-fluoroacetate PET/CT as a tumor-imaging modality: preclinical study in healthy volunteers and clinical evaluation in patients with liver tumor by Kenji Takemoto; Etsuro Hatano; Ryuichi Nishii; Shinya Kagawa; Yoshihiko Kishibe; Masaaki Takahashi; Hiroshi Yamauchi; Kazuyoshi Matsumura; Masazumi Zaima; Kan Toriguchi; Kazutaka Tanabe; Koji Kitamura; Satoru Seo; Kojiro Taura; Keigo Endo; Shinji Uemoto; Tatsuya Higashi (371-380).
Although [18F]-FDG is a useful oncologic PET tracer, FDG uptake is known to be low in a certain type of hepatocellular carcinoma (HCC). [18F]-fluoroacetate (18F-FACE) is an [18F] fluorinated acetate, which is known to be converted into fatty acids, incorporated in membrane and is expected to be a promising oncologic PET tracer. The aim of this study was to evaluate the usefulness of 18F-FACE as an oncologic PET tracer in preclinical study in healthy volunteers and in patients with liver tumors.Twenty-four healthy volunteers (age 48.2 ± 12.9 years old; 15 male and 9 female) and ten patients with liver tumor (age 72.1 ± 7.0 years old; 6 male and 4 female) were included. We performed whole-body static PET/CT scan using 18F-FACE (n = 34) and 18F-FDG (n = 5 for volunteers, n = 8 for patients) on each day, respectively. Qualitative analysis and quantitative analysis of tumors (5 HCCs, 1 cholangiocellular carcinoma, 4 metastatic tumors from colon cancer and P-NET) were performed using SUVmax and tumor-to-normal liver ratio (TNR).In healthy volunteers, 18F-FACE was metabolically stable in vivo and its biodistribution was almost similar to blood pool, basically uniformly independent of age and gender during PET scan time (up to 3 h). Normal physiological uptake of 18F-FACE at each organ including liver (SUVmean 1.8 ± 0.2) was lower than that of blood pool (SUVmean 2.3 ± 0.3) at 1 h after injection. Chronic inflammatory uptake around femur of post-operative state of femoral osteotomy and faint uptake of benign hemangioma were observed in a case of healthy volunteer. 18F-FACE (SUVmax 2.7 ± 0.6, TNR 1.5 ± 0.4) of liver tumors was significantly lower than those of 18F-FDG uptake (6.5 ± 4.2, 2.6 ± 1.7, respectively). In qualitative analysis, 18F-FDG was positive in 4 tumors (3 HCCs, 1 CCC) and negative in the other 6 tumors, while 18F-FACE was also positive in 4 tumors which were the same tumors with positive 18F-FDG uptake.Biodistribution of 18F-FACE was appropriate for oncologic imaging. Tumor 18F-FACE uptake was positive in four patients with HCC and CCC, but the uptake pattern was similar to 18F-FDG. Further evaluation was needed.
Keywords: Fluoroacetate; Hepatocellular carcinoma; Fluorodeoxyglucose; Healthy volunteers; Positron emission tomography

A case of septic pulmonary embolism associated with renal abscess mimicking pulmonary metastases of renal malignancy by Jo Sung Jung; Sang Mi Lee; Han Jo Kim; Si-Hyong Jang; Jeong Won Lee (381-385).
We report the case of a 46-year-old woman with acute febrile symptom who had multiple pulmonary nodules and a renal mass. She underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to find a hidden malignancy and the cause of her fever. FDG PET/CT images demonstrated a renal mass and multiple lung nodules with intense FDG uptake, which was suspicious of a renal malignancy with multiple pulmonary metastatic lesions. CT-guided biopsies of the pulmonary and renal lesions only showed chronic inflammatory infiltrates without evidence of malignancy. She was diagnosed with septic pulmonary embolism from a renal abscess. One month after antibiotic treatment, the follow-up chest and abdomen CT showed improvement of the lung and renal lesions. This is the first case demonstrating the FDG PET/CT finding of septic pulmonary embolism associated with renal abscess in the published literature.
Keywords: 18F-fluorodeoxyglucose; PET; Septic pulmonary embolism; Renal abscess

To quantify the differential effects of chemotherapy on the metabolic activity of skeletal muscle in vivo using molecular imaging with [18F]-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT).In this retrospective study, 21 subjects with stage IV melanoma who underwent pre- and post-chemotherapy whole-body FDG-PET/CT imaging were included. The mean standardized uptake value (SUVmean) of 8 different skeletal muscles was measured per subject. Pre- and post-treatment measurements were then averaged across all subjects for each muscle and compared for statistically significant differences between the muscles and following different chemotherapy regimens including dacarbazine (DTIC) and temozolomide (TMZ).Analysis of FDG-PET/CT images reliably detected changes in skeletal muscle metabolic activity based on muscle location. The percent change in metabolic activity of each skeletal muscle in each subject following chemotherapy was observed to be related to the type of chemotherapy received. Subjects receiving DTIC generally had a decrease in metabolic activity of all muscle groups, whereas subjects receiving TMZ generally had an increase in muscle activity of all muscle groups.FDG-PET/CT can reveal baseline metabolic differences between different muscles of the body. Different chemotherapies are associated with differential changes in the metabolic activity of skeletal muscle, which can be detected and quantified with FDG-PET/CT.
Keywords: FDG; PET; Skeletal muscle; Metabolism; Chemotherapy

Recommendations for 18F-fluorodeoxyglucose positron emission tomography imaging for cardiac sarcoidosis: Japanese Society of Nuclear Cardiology Recommendations by Yoshio Ishida; Keiichiro Yoshinaga; Masao Miyagawa; Masao Moroi; Chisato Kondoh; Keisuke Kiso; Shinichiro Kumita (393-403).