Initial Physician Experience with [18F]Flutemetamol Amyloid PET Imaging Following Availability for Routine Clinical Use in Japan.

BACKGROUND: Brain amyloid is a neuropathological hallmark of Alzheimer's disease (AD). By visualizing brain amyloid, positron emission tomography (PET) may influence the diagnostic assessment and management of patients with cognitive impairment. OBJECTIVE: As part of a Japanese post-approval study to measure the safety of [18F]flutemetamol PET, the association of amyloid PET results with changes in diagnosis and diagnostic confidence was assessed. METHODS: Fifty-seven subjects were imaged for amyloid PET using [18F]flutemetamol at a single Japanese memory clinic. The cognitive diagnosis and referring physician's confidence in the diagnosis were recorded before and after availability of PET results. Imaging started approximately 90 minutes after [18F]flutemetamol administration with approximately 185 MBq injected. PET images were acquired for 30 minutes. RESULTS: Amyloid PET imaging led to change in diagnosis in 15/44 clinical subjects (34%). Mean diagnostic confidence increased by approximately 20%, from 73% pre-scan to 93% post-scan, and this rise was fairly consistent across the main patient subgroups (mild cognitive impairment, AD, and non-AD) irrespective of the pre-scan diagnosis and scan result. CONCLUSION: The study examined the utility of amyloid PET imaging in a Japanese clinical cohort and highlighted the use of an etiological diagnosis in the presence of the amyloid scan. [18F]Flutemetamol PET led to a change in diagnosis in over 30% of cases and to an increase in diagnostic confidence by approximately 20% consistent with other reports.

Scatter Correction with Combined Single-Scatter Simulation and Monte Carlo Simulation Scaling Improved the Visual Artifacts and Quantification in 3-Dimensional Brain PET/CT Imaging with 15O-Gas Inhalation.

In 3-dimensional PET/CT imaging of the brain with 15O-gas inhalation, high radioactivity in the face mask creates cold artifacts and affects the quantitative accuracy when scatter is corrected by conventional methods (e.g., single-scatter simulation [SSS] with tail-fitting scaling [TFS-SSS]). Here we examined the validity of a newly developed scatter-correction method that combines SSS with a scaling factor calculated by Monte Carlo simulation (MCS-SSS). Methods: We performed phantom experiments and patient studies. In the phantom experiments, a plastic bottle simulating a face mask was attached to a cylindric phantom simulating the brain. The cylindric phantom was filled with 18F-FDG solution (3.8-7.0 kBq/mL). The bottle was filled with nonradioactive air or various levels of 18F-FDG (0-170 kBq/mL). Images were corrected either by TFS-SSS or MCS-SSS using the CT data of the bottle filled with nonradioactive air. We compared the image activity concentration in the cylindric phantom with the true activity concentration. We also performed 15O-gas brain PET based on the steady-state method on patients with cerebrovascular disease to obtain quantitative images of cerebral blood flow and oxygen metabolism. Results: In the phantom experiments, a cold artifact was observed immediately next to the bottle on TFS-SSS images, where the image activity concentrations in the cylindric phantom were underestimated by 18%, 36%, and 70% at the bottle radioactivity levels of 2.4, 5.1, and 9.7 kBq/mL, respectively. At higher bottle radioactivity, the image activity concentrations in the cylindric phantom were greater than 98% underestimated. For the MCS-SSS, in contrast, the error was within 5% at each bottle radioactivity level, although the image generated slight high-activity artifacts around the bottle when the bottle contained significantly high radioactivity. In the patient imaging with 15O2 and C15O2 inhalation, cold artifacts were observed on TFS-SSS images, whereas no artifacts were observed on any of the MCS-SSS images. Conclusion: MCS-SSS accurately corrected the scatters in 15O-gas brain PET when the 3-dimensional acquisition mode was used, preventing the generation of cold artifacts, which were observed immediately next to a face mask on TFS-SSS images. The MCS-SSS method will contribute to accurate quantitative assessments.

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.

PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

The usefulness of (18)F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD).

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for MTX-LPD. METHODS: We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by (18)F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of (18)F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX. RESULTS: MTX-LPD lesions were observed in 92/324 (28.4 %) regions. (18)F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8-47.1), 44.3 (range 0-362.6) ml, 181.8 (range 0-2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0-24.9), 15.7 (range 0-250.1) ml, and 97.4 (range 0-1052.1) ml. CONCLUSIONS: Although (18)F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the (18)F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX.

Metabolic Activity of Red Nucleus and Its Correlation with Cerebral Cortex and Cerebellum: A Study Using a High-Resolution Semiconductor PET System.

UNLABELLED: The red nucleus (RN) is a pair of small gray matter structures located in the midbrain and involved in muscle movement and cognitive functions. This retrospective study aimed to investigate the metabolism of human RN and its correlation to other brain regions. METHODS: We developed a high-resolution semiconductor PET system to image small brain structures. Twenty patients without neurologic disorders underwent whole-brain scanning after injection of 400 MBq of (18)F-FDG. The individual brain (18)F-FDG PET images were spatially normalized to generate a surface projection map using a 3-dimensional stereotactic surface projection technique. The correlation between the RN and each voxel on the cerebral and cerebellar cortices was estimated with Pearson product-moment correlation analysis. RESULTS: Both right and left RNs were visualized with higher uptake than that in the background midbrain. The maximum standardized uptake values of RN were 7.64 ± 1.92; these were higher than the values for the dentate nucleus but lower than those for the caudate nucleus, putamen, and thalamus. The voxel-by-voxel analysis demonstrated that the right RN was correlated more with ipsilateral association cortices than contralateral cortices, whereas the left RN was equally correlated with ipsilateral and contralateral cortices. The left RN showed a stronger correlation with the motor cortices and cerebellum than the right RN did. CONCLUSION: Although nonspecific background activity around RNs might have influenced the correlation patterns, these metabolic relationships suggested that RN cooperates with association cortices and limbic areas to conduct higher brain functions.

Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients.

PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging.

PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.

Postoperative assessment of hepatic asialoglycoprotein receptor function with Tc-99m GSA: the safety margin of resection size in living donor liver transplantation.

BACKGROUND: Living liver donation is associated with size-dependent complications. The resectable size and its safety margin should be defined for the safety of donors. The purpose of the present study was to determine if the current partial hepatectomies are done under the safety margin of the resectable size, by measuring asialoglycoprotein receptor (ASGPR) function of donor's remnant liver. MATERIAL AND METHODS: Seventy-four living donors (age 35±11 years) underwent Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m GSA) scintigraphy at postoperative week 1. We evaluated the scintigraphic results using established parameters of GSA uptake (LHL15) and its clearance from the blood pool (HH15). Based on the literature, we consider HH15 <0.55 to indicate normal ASGPR function, and 0.55£ HH15 <0.65 to indicate mild impairment. In terms of the hepatic uptake, we consider LHL15>0.93 to indicate normal ASGPR function, and 0.87< LHL15 £0.93 to indicate mild impairment. RESULTS: The average resected size was 337±170 mL, corresponding to 28±12% of the original donor's whole liver volume. No donors showed 0.65≤ HH15 or LHL15 <0.87, suggesting moderate or severely impaired ASGPR function. However, larger resection size (35-53%) was positively associated with higher HH15 values (R=0.53, p<0.001). In the range of HH15 (0.35-0.64) among present donors, higher HH15 values did not affect the regeneration volume (R=0.03, p=NS). CONCLUSIONS: Larger partial resection (≥35% of the original liver volume) may impair postsurgical ASGPR function, but smaller resection (<35%) was considered to be under the safety margin of the hepatectomy. Although mildly impaired postsurgical ASGPR function did not indicate poor prognosis, careful attention may be required for donors undergoing larger (³35%) partial resection.

FDG PET performed at thyroid remnant ablation has a higher predictive value for long-term survival of high-risk patients with well-differentiated thyroid cancer than radioiodine uptake.

PURPOSE: The predictive value of FDG PET at thyroid remnant ablation was evaluated in comparison to radioiodine uptake in high-risk patients with differentiated thyroid cancer. PATIENTS AND METHODS: One hundred forty-one patients who underwent radioiodine therapy (RIT) after total thyroidectomy and received at least 1 further RIT due to suspected metastases were retrospectively analyzed. Patients had not received RIT previously. FDG PET was performed before thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg between the first and second RIT, ΔTg). RESULTS: Biochemical response could be evaluated in 80 patients; survival data could be obtained for 88 patients (maximum, 124 months). Biochemical response was significantly better in patients with radioiodine-positive metastases compared with patients with radioiodine-negative metastases (median ΔTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding survival, deaths occurred later in patients with radioiodine-positive metastases compared with radioiodine-negative patients; however, there was no significant difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05). Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer biochemical response compared with patients with FDG-negative metastases (median ΔTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P < 0.05). CONCLUSIONS: At thyroid remnant ablation, FDG PET is more predictive for long-term survival, whereas radioiodine uptake is more important for short-term response. FDG PET performed at thyroid remnant ablation might represent a useful tool for management of high-risk patients with differentiated thyroid cancer.

18F-FDG-PET/CT better localizes active spinal infection than MRI for successful minimally invasive surgery.

BACKGROUND: Surgical debridement is often required to treat spinal infections. Successful surgery requires accurate localization of the active infections, however, current imaging technique still requires surgeons' experience to narrow the surgical fields to achieve less invasive procedures. PURPOSE: To investigate the use of F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for successful surgical planning. MATERIAL AND METHODS: Nine patients with suspected spinal infection underwent magnetic resonance imaging (MRI) and FDG-PET/CT before surgery to locate active foci of infections. The spinal structures were divided into seven compartments at each intervertebral disc level for a total of 315 compartments investigated. The same classification system was used to design operating fields for histological correlation. RESULTS: FDG-PET/CT diagnosed fewer compartments as active infection (34 compartments, 10.8%) than MRI (62 compartments, 19.7%, P = 0.002). Surgical exploration was performed in 49 compartments, and demonstrated active infection in 25 compartments. The sensitivity / specificity of FDG-PET/CT was 100% / 79%, respectively, which was superior to those of MRI, 76% / 42%. Foci of active infection showed hypermetabolic activity with a SUVmax of 7.1 ± 2.6 (range, 3.0-12.7). Receiver operating characteristic (ROC) analysis indicated an optimal threshold for active spinal infection at a SUVmax of 4.2, corresponding to a sensitivity of 90.3% and specificity of 91.2%. CONCLUSION: FDG-PET/CT demonstrated limited areas of abnormality allowing accurate delineation, and is thus useful to narrow the surgical fields. Since overall diagnostic accuracy of FDG-PET/CT was superior to that of MRI, FDG-PET/CT is a useful technique to narrow the surgical field for successful less invasive surgery.

FDG PET/CT diagnostic criteria may need adjustment based on MRI to estimate the presurgical risk of extrapelvic infiltration in patients with uterine endometrial cancer.

PURPOSE: The staging of endometrial cancer requires surgery which carries the risk of morbidity. FDG PET/CT combined with anatomical imaging may reduce the number of unnecessary lymphadenectomies by demonstrating the risk of extrapelvic infiltration. The purpose of this study was to optimize FDG PET/CT diagnostic criteria for risk assessment in endometrial cancer after first-line risk triage with MRI. METHODS: The study population comprised 37 patients who underwent curative surgery for the treatment of endometrial cancer. First, the risk of extrapelvic infiltration was triaged using MRI. Second, multiple glucose metabolic profiles of the primary lesion were assessed with FDG PET/CT, and these were correlated with the histopathological risk of extrapelvic infiltration including lymphovascular space invasion (LVSI) and high-grade malignancy (grades 2 and 3). The results of histological correlation were used to adjust FDG PET/CT diagnostic criteria. RESULTS: Presurgical assessment using MRI was positive for deep (>50 %) myometrial invasion in 17 patients. The optimal FDG PET/CT diagnostic criteria vary depending on the results of MRI. Specifically, SUVmax (≥16.0) was used to indicate LVSI risk with an overall diagnostic accuracy of 88.2 % in patients with MRI findings showing myometrial invasion. High-grade malignancy did not correlate with any of metabolic profiles in this patient group. In the remaining patients without myometrial invasion, lesion glycolysis (LG) or metabolic volume were better indicators of LVSI than SUVmax with the same diagnostic accuracy of 80.0 %. In addition, LG (≥26.9) predicted high-grade malignancy with an accuracy of 72.2 %. Using the optimized cut-off criteria for LVSI, glucose metabolic profiling of primary lesions correctly predicted lymph node metastasis with an accuracy of 73.0 %, which was comparable with the accuracy of visual assessment for lymph node metastasis using MRI and FDG PET/CT. CONCLUSION: FDG PET/CT diagnostic criteria may need adjustment based on the anatomical information provided by MRI. The optimized criteria can predict the risk of pathology-proven LVSI correctly in 83.8 % of patients before surgery, and thus would improve presurgical treatment planning.

FDG-PET may predict the effectiveness of hyperbaric oxygen therapy in a patient with bisphosphonate-related osteonecrosis of the jaw: report of a case.

We report an advanced case of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in an osteoporotic patient treated with oral risedronate sodium for 2 years. An 80-year-old woman presented to our hospital complaining of pain, swelling and pus discharge in the lower alveolar ridge. Fluorine-18 labeled fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy showed definite uptake in the mandible. Under clinical diagnosis of BRONJ, we applied systematic treatments including antibiotic therapy, irrigation, cessation of bisphosphonate, hyperbaric oxygen (HBO) therapy, and debridement of necrotic bone. After pre-operative 20 sessions of HBO therapy, her clinical symptoms disappeared. SUVmax of FDG-PET decreased definitely from 4.5 to 2.5, although magnetic resonance image and bone scintigraphy did not show remarkable changes. After minor surgery with debridement of necrotic bone, she received another ten sessions of HBO therapy. After the treatment, her clinical course was excellent. In conclusion, this report demonstrates FDG-PET may predict the effect of HBO therapy in BRONJ.

Evaluation of delineation of image details in semiconductor PET utilizing the normalized mutual information technique.

OBJECTIVE: PET using semiconductor detectors provides high-quality images of the human brain because of its high spatial resolution. To quantitatively evaluate the delineation of image details in clinical PET images, we used normalized mutual information (NMI) to quantify the similarity with images obtained through MRI. NMI is used to evaluate image quality by determining similarity with a reference image. The aim of this study was to evaluate quantitatively the delineation of image details provided by semiconductor PET. MATERIALS AND METHODS: To quantitatively evaluate anatomical delineation in clinical PET images, MRI scans of patients were used as T1-weighted images. [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET brain images were obtained from six patients using (a) a Hitachi semiconductor PET scanner and (b) a ECAT HR+ scintillator PET scanner. The NMI calculated from the semiconductor PET and MRI was denoted by NMIsemic, whereas the NMI calculated from conventional scintillator PET and MRI was denoted by NMIconve. The higher the value of NMI, the greater the similarity to MRI. RESULTS: NMIsemic ranged from 1.22 to 1.29, whereas NMIconve ranged from 1.13 to 1.18 (P<0.05). Furthermore, all the NMI values of the semiconductor PET were higher than those of the conventional scintillator PET. CONCLUSION: Utilizing NMI, we quantitatively evaluated the delineation of image details in clinical PET images. The results reveal that semiconductor PET has superior anatomical delineation and physical performance compared with conventional scintillator PET. This improved delineation of image details makes semiconductor PET promising for clinical applications.

Electrocardiographically gated ¹¹C-hydroxyephedrine PET for the simultaneous assessment of cardiac sympathetic and contractile functions.

OBJECTIVE: Application of the electrocardiographically (ECG) gated positron emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow the simultaneous assessment of cardiac sympathetic and contractile functions. However, there are uncertainties regarding the diagnostic accuracy of left ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this study was to clarify the minimal requirement of count statistics to measure LV volumes with ECG-gated HED-PET and to investigate the reliability of the measurements. METHODS: Five healthy volunteers and 11 patients with heart failure underwent a 40-min list-mode PET scan after an injection of HED (197 ± 35 MBq). The list-mode data were histogrammed into multiple sets of acquisition periods at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into corresponding gated images using an iterative algorithm. The LV end-diastolic volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction (LVEF) were calculated in each acquisition period. These values were compared with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects of HED retention on the accuracy of the volume measurements were investigated. RESULTS: Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images. The lower counts resulted in underestimation in the volume measurements. Reasonably accurate volume measurements required equal to or greater than 6.0 Mcount/bin. This corresponded to 7.0 ± 1.9 min (range, 4.0-10.3 min) for the acquisition period. Volumetric results using the 6.0 Mcount/bin data highly correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p < 0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the volumetric results compared to the MRI volumetry. CONCLUSIONS: The volumetric accuracy with ECG-gated HED-PET was affected by the count statistics rather than the HED retention. LV volume measurements were feasible with 10-min acquisition period for most of the patients. This technique allows the simultaneous assessment of cardiac sympathetic and contractile functions without the need for an additional injection or scanning time, thus reducing overall costs for diagnostic imaging.

Brain regions associated with cognitive impairment in patients with Parkinson disease: quantitative analysis of cerebral blood flow using 123I iodoamphetamine SPECT.

PURPOSE: Cognitive impairment is a representative neuropsychiatric presentation that accompanies Parkinson disease (PD). The purpose of this study was to localize the cerebral regions associated with cognitive impairment in patients with PD using quantitative SPECT. PATIENTS AND METHODS: Thirty-two patients with PD (mean [SD] age, 75 [8] years; 25 women; Hoehn-Yahr scores from 2 to 5) underwent quantitative brain SPECT using 123I iodoamphetamine. Parametric images of regional cerebral blood flow (rCBF) were spatially normalized to the standard brain atlas. First, voxel-by-voxel comparison between patients with PD with versus without cognitive impairment was performed to visualize overall trend of regional differences. Next, the individual quantitative rCBF values were extracted in representative cortical regions using a standard region-of-interest template to compare the quantitative rCBF values. RESULTS: Patients with cognitive impairment showed trends of lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices in the voxel-by-voxel analyses. Region-of-interest-based analysis demonstrated significantly lower rCBF in the bilateral anterior cingulate cortices (right, 25.8 [5.5] vs 28.9 [5.7] mL per 100 g/min, P < 0.05; left, 25.8 [5.8] vs 29.1 [5.7] mL per 100 g/min, P < 0.05) associated with cognitive impairment. CONCLUSIONS: Patients with cognitive impairment showed lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices. The results suggested dysexecutive function as an underlining mechanism of cognitive impairment in patients with PD.

Diagnostic accuracy of lymph node metastasis depends on metabolic activity of the primary lesion in thoracic squamous esophageal cancer.

UNLABELLED: The metabolic activity of the primary tumor is an important variable in (18)F-FDG PET interpretation for presurgical staging, because this activity is likely to affect the possibility of detection of malignant involvement in lymph nodes (LNs). The purpose of this study was to reevaluate the diagnostic accuracy of (18)F-FDG PET/CT for the presurgical staging of esophageal squamous cell carcinoma (SCC) in correlation with the (18)F-FDG avidity of the primary lesions. METHODS: One hundred fifty-six patients (mean age ± SD, 61.4 ± 8.0 y) underwent (18)F-FDG PET/CT before surgical esophagectomy and LN dissection. LN metastasis was identified using the fusion of PET and CT images with increased (18)F-FDG uptake greater than the background activity of the adjacent structures. The results of the patients' (18)F-FDG PET/CT examinations for LN involvement were compared with the histopathologic results to investigate the diagnostic accuracy of (18)F-FDG PET/CT for tumor staging. In addition, we examined the correlation between the diagnostic accuracy of (18)F-FDG PET/CT for LN involvement and the (18)F-FDG avidity of the primary lesions, to investigate the effect of tumor aggressiveness on the diagnosis of LN metastasis. RESULTS: The diagnostic accuracy of (18)F-FDG PET/CT for LN metastasis showed a low sensitivity, ranging from 29.3% to 53.3%, whereas the specificity was higher than 89.8% in regional thoracic nodes and in remote areas of the cervical and abdominal regions. The (18)F-FDG uptake of the primary lesions positively correlated with that of the metastatic LNs in the thoracic field (R = 0.52, P < 0.05). As a result, our receiver-operating-characteristic analyses demonstrated an area under the curve value of 0.73, with the optimal cutoff value at a maximum standardized uptake value of 3.3 in patients with mid to high (18)F-FDG avidity in the primary lesions (maximum standardized uptake value ≥ 5). CONCLUSION: This study showed that the avidity of the primary esophageal SCCs affected the detectability of lymph nodal metastases. If primary lesions of esophageal SCC present with a low (18)F-FDG uptake, PET/CT may have a limited role for initial staging because of low sensitivity to detect lymph node metastases.

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin's lymphoma: radiation dose to the testes.

PURPOSE: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. MATERIALS AND METHODS: Testicular uptake and retention of (131)I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54 ± 11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using (131)I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. RESULTS: The absorbed dose to the testes showed considerable variability (range = 4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6 ± 1.8 nmol/l (pre-RIT) vs. 3.8 ± 2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (≥ 25 Gy) showed a greater reduction [4.7 ± 1.6 nmol/l (pre-RIT) vs. 3.3 ± 2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. CONCLUSION: The testicular radiation absorbed dose varied highly among individual patients. Patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.

¹8F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas.

PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that (18)F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. METHODS: This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and (18)F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. RESULTS: Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p ≤ 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 ± 0.60, range 1.71-3.81) than in non-GBM patients (1.22 ± 0.06, range 1.09-1.29, p ≤ 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also higher in GBM patients (1.46 ± 0.75, range 0.91-3.79) than in non-GBM patients (1.07 ± 0.62, range 0.66-2.95, p ≤ 0.05); however, overlap of the ranges did not allow clear differentiation between GBM and non-GBM. The uptake volume of FMISO was larger in GBM (27.18 ± 10.46%, range 14.02-46.67%) than in non-GBM (6.07 ± 2.50%, range 2.12-9.22%, p ≤ 0.001). CONCLUSION: These preliminary data suggest that FMISO PET may distinguish GBM from lower grade gliomas.

Risk evaluation for coronary artery disease in patients with impaired glucose tolerance after a successful coronary intervention.

PURPOSE: Patients with coronary artery disease (CAD) often have risk factors that may influence endothelial function. The purpose of this study was to evaluate the endothelial function and its association with coronary risk factors after percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A total of 14 patients with impaired glucose tolerance and CAD underwent positron emission tomography with N-13 ammonia to measure myocardial blood flow (MBF) at rest and during a cold pressor test (CPT), to estimate endothelial function as a percent increase (%increase) of MBF. The results were compared among normal segments (normal), reperfused segments with PCI (PCI), and nonculprit CAD segments without PCI (non-PCI). Correlations between the %increase and major risk factors were also investigated. RESULTS: CPT induced significant increase in MBF in all groups. The %increase of normal, non-PCI, and PCI groups were 33% ± 22%, 21% ± 23%, and 26% ± 23%, respectively. Comparison with risk factors demonstrated significant correlations only in the non-PCI group. Specifically, there were negative correlations between %increase and fasting blood sugar (r = -0.64, P < 0.05), hemoglobin A1c (r = -0.74, P < 0.05), total cholesterol (r = -0.87, P < 0.05), triglyceride (r = -0.71, P < 0.05), and low-density lipoprotein cholesterol (r = -0.92, P < 0.005), respectively. CONCLUSIONS: Although impaired glucose tolerance patients with a PCI-treated coronary stenosis showed preserved response to CPT, the %increase negatively correlated with risk factors in the non-PCI segments. Therefore, coronary risk factors may affect CAD lesions in PCI-treated patients.