Improvement of motion artifacts using dynamic whole-body 18F-FDG PET/CT imaging.

PURPOSE: Serial dynamic whole-body PET imaging is valuable for assessing serial changes in tracer uptake. The purpose of this study was to evaluate the improvement of motion artifacts in patients using serial dynamic whole-body 18F-fluorodeoxyglyucose (FDG) PET/CT imaging. MATERIALS AND METHODS: In 797 consecutive patients, serial 3-min dynamic whole-body FDG PET imaging was performed seven times, at 60 or 90 min after FDG administration. In cases with large body motion during imaging, we tried to improve the images by summing the images before body motion. An image quality study was performed on another 50 patients without obvious body motion using the same acquisition mode. RESULTS: Obvious body movement was observed in 106 of 797 cases (13.3%), and severe motion artifacts which interfered image interpretation were observed in 18 (2.3%). In these 18 cases, summation of the images before the body movement enabled us to obtain images that excluded the effect of the body motion. In the visual evaluation of the image quality in another 50 patients studied, acceptable image quality was obtained when 2 or more times the serial 3-min image data were added. CONCLUSION: Serial dynamic whole-body FDG PET imaging can minimize body motion artifacts by summation of the images before the body motion. Such serial dynamic study may be a choice for PET imaging to eliminate motion artifacts.

[THE USEFULNESS OF POSITRON EMISSION TOMOGRAPHY / COMPUTED TOMOGRAPHY IN THE DIAGNOSIS OF METASTASIS IN PATIENTS WITH UROTHELIAL CARCINOMA].

(Purpose) This study examined the usefulness of positron emission tomography (PET) / computed tomography (CT) in the diagnosis of metastasis in patients with urothelial carcinoma. (Materials and methods) The subjects were patients who were newly diagnosed with urothelial carcinoma in our department on whom we performed CT and PET/CT to search for metastasis. (Results) The median age of the 92 subjects was 71 years, and bladder and upper tract urotherial cancer were underlying diseases in 41 (46%) and 51 (54%) patients, respectively. In 66 (72%) of the 92 cases, no metastasis was observed by CT, while PET/CT revealed metastasis in 9 (14%). The 57 (86%) patients in whom both CT and PET/CT showed no metastasis underwent radical surgery, while 2 patients (4%) exhibited pathological lymph node metastasis.Of the 26 patients in whom CT revealed metastasis, PET/CT showed no metastasis in 3 (12%), and the absence of pathological metastasis was confirmed in all patients. Of the 23 patients found to have metastasis in both CT and PET/CT, metastasis that could not be identified by CT was discovered by performing PET/CT in 10 (43%) patients.PET/CT showed significantly higher diagnostic accuracy than CT alone (p< 0.01), with sensitivities of 94.1% and 67.6%, specificities of 100% and 94.8%, and positive diagnosis rates of 97.8% and 84.7%, respectively. (Conclusions) PET/CT in patients with urothelial cancer revealed that metastases that cannot be diagnosed by CT alone are found at a significant frequency. Since these metastases can affect treatment choices in patients with urothelial cancer, PET/CT is considered to be useful in diagnosing patients with urothelial cancer.

18F-FDG-PET/CT as an imaging biomarker for regorafenib efficacy in metastatic colorectal cancer (JACCRO CC-12).

INTRODUCTION: Regorafenib is a multikinase inhibitor approved for the treatment of metastatic colorectal cancer (mCRC). Despite providing a statistically significant survival benefit, a substantial number of patients fail to respond to or continue with treatment, which has resulted in an unmet clinical need for a biomarker of regorafenib efficacy. METHODS: The JACCRO CC-12 study was a prospective, multicenter, single-arm phase II trial designed to evaluate the usefulness of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) as an imaging biomarker of regorafenib in patients with mCRC that progressed after standard chemotherapies. FDG-PET and contrast-enhanced computed tomography (CT) were performed before and after treatment with regorafenib 160 mg once daily 3 weeks on/1 week off. The primary end point was the change in the maximum standardized uptake value in the lesion with the highest uptake at pre-treatment FDG-PET. The secondary end points included overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), safety, and the correlation between FDG-PET and CT. RESULTS: Twenty patients were enrolled from November 2014 to March 2016, 17 of whom were evaluated for metabolic and morphological changes. Metabolic response with FDG-PET was partial response (PR) in one case (5.9%), stable disease (SD) in four (23.5%), and progressive disease (PD) in 12 (70.6%). The metabolic response rate was 5.9%. On CT imaging, no complete response or PR was observed, and the ORR was 0%. Median PFS and OS were 1.7 and 9.8 months, respectively. The median PFS of patients who achieved PR or SD by FDG-PET was 3.7 months, whereas that of those assessed as PD was 1 month (p = 0.13). The median OS of patients who achieved PR or SD by FDG-PET was 13.0 months, whereas that of patients assessed as PD was 10.6 months (p = 0.43). Frequent adverse events were palmar-plantar erythrodysesthesia syndrome, hypertension, loss of appetite, and fatigue. CONCLUSIONS: In this study, FDG-PET failed to demonstrate usefulness as an early imaging biomarker of regorafenib in patients with mCRC.

Dynamic Whole-Body 18F-FDG PET for Minimizing Patient Motion Artifact.

Recent PET/CT systems permit short acquisition with acceptable image quality. In addition, continuous-bed-motion mode is available for whole-body PET imaging with some PET cameras providing better uniformity and reproducibility throughout the field of view. We demonstrate a case with patient motion during the dynamic scan. Although the total summation of serial whole-body scan showed image artifact, the first 15 minutes' summation of the serial scans provided high-quality images by eliminating the frames with motion. This acquisition mode seems to be particularly useful to perform for those who may likely to move during PET scan.

Simultaneous occurrence of distant metastases to the small intestine and the thoracic esophagus from anaplastic thyroid carcinoma: a case report.

Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy and characterized by spreading to regional lymph nodes and distant metastases, but we were unable to find a previous report of simultaneous metastases of transformed ATC to either the small intestine or thoracic esophagus in the English language literature. A 60-year-old man suffered from well-differentiated thyroid carcinoma and underwent total thyroidectomy. Eight years later, local recurrence of thyroid cancer showed intense fluorodeoxyglucose/positron emission tomography (FDG-PET) uptake at the paratracheal region, which was suspected as a remnant tumor of the thyroid that transformed from differentiated to ATC. At that time, the patient underwent resection of the small intestine to remove an abdominal mass and consequently developed stenosis of the thoracic esophagus caused by the esophageal tumor. Histological scrutiny of specimens from both tumors in the small intestine and thoracic esophagus demonstrated the same pattern as that of undifferentiated carcinoma. Regarding histological verification and a change in the FDP-PET uptake level, it is strongly possible that our case demonstrated coincident metastases of ATC to both the small intestine and esophagus. In conclusion and to the best of our knowledge, this report is the first to present evidence suggesting that ATC has the potential to metastasize to any organs, including the digestive tract.

[Evaluation of the product-specific standard input function for the IMP-ARG method].

To confirm the previous reports demonstrating the difference in the octanol extraction fractions between the currently available two N-isopropyl-4-iodoamphetamine (123I) products (IMP(A) and IMP(B)), we newly developed the standard input function for IMP(B) in 19 healthy volunteers and compared it with the established standard input function, which has been originally generated with IMP(A). The octanol extraction fractions of IMP(B) were stable from 5 minutes to 16 minutes post injection and significantly higher than those of IMP(A). The mCBFs calculated with IMP(B) by using the established standard input function for IMP(A) tended to be higher than those with the combination of IMP(A) and the established standard input function though the difference was not significant. When measured with IMP(B) combined with the correspondent standard input function, mCBFs were identical to those calculated with IMP(A) with the established standard input function, suggesting that the appropriate standard input function should be used according to the product used.

Temporal and topographic profiles of cyclooxygenase-2 expression during 24 h of focal brain ishemia in rats.

Substantial increases in cyclooxygenase-2 (COX-2) mRNA and protein levels were demonstrated in the peri-infarct and focal ischemic areas after 3-24 and 12-24 h, respectively, in rats. In the ischemic core, significant increases in COX-2 mRNA followed 6 h of ischemia, though the peak level was about one-third of that in the peri-infarct area. Increases in COX-2 protein in the ischemic core were not observed during ischemic periods. Diffuse, neuronal COX-2 staining was found in peri-infarct areas as well as in discrete, immunoreactive neurons in the ischemic core. Robust increases in prostaglandin E2 levels in the peri-infarct area were demonstrated following 24 h of ischemia. Prostaglandin production as well as COX-2 expression in ischemic tissues depended on the degree and duration of the reduction in cerebral blood flow.

Use of a standardized uptake value for parametric in vivo imaging of benzodiazepine receptor distribution on [11C]flumazenil brain PET.

To simplify the acquisition protocol of carbon-11 labeled flumazenil (FMZ) positron emission tomography (PET) for distribution volume (DV) images, we attempted to obtain standardized uptake value (SUV) images compatible with DV images, and assessed the applicability of this method in patients with unilateral cerebrovascular diseases (CVD). [(11)C]FMZ PET was performed in ten normal subjects. A DV image and ten sequential 5-min SUV images were generated for each subject. We investigated the correlation coefficient (r) and standard estimation of error (SEE) between the latter ten static images and the DV image using the pixel-by-pixel method, thereby determining the optimum acquisition phase. The same FMZ PET procedure was performed in 15 patients with unilateral CVD. Twenty regions of interest (ROIs) were positioned both in lesioned areas and in symmetrical regions. DV and SUV in the optimum phase for each ROI were calculated to compare the lesion-to-normal (L/N) ratio of DV and that of SUV. The highest r and a low SEE (r=0.957, SEE=633) were observed from 30 to 35 min after tracer administration in the study of normal subjects. A high r (0.945) and a low SEE (0.0438) between the DV L/N ratio and the SUV L/N ratio were obtained in the study of patients. Our study suggests that SUV images acquired from 30 to 35 min after FMZ administration are a suitable alternative to DV images not only in normal subjects but also in patients with unilateral CVD. This simple method seems to be valuable for the identification of altered neuronal activity in patients with CVD.

Characterisation of [123I]iomazenil distribution in a rat model of focal cerebral ischaemia in relation to histopathological findings.

Iodine-123 labelled iomazenil ([(123)I]IMZ) has been reported to be a useful marker of neuronal viability. The brain distribution of [(123)I]IMZ, however, has not been correlated with the pathophysiological response in detail after an ischaemic insult. To characterise [(123)I]IMZ as a marker of neuronal viability, we compared its brain distribution with cyclooxygenase-2 (COX-2) expression, DNA fragmentation and cellular integrity. [(123)I]IMZ and [(125)I]IMP were injected into rats with focal cerebral ischaemia for the purpose of dual-tracer autoradiography. COX-2 and microtubule-associated protein-2 (MAP-2, a marker of cellular integrity) were immunostained. In situ DNA polymerase-I-dependent dUTP incorporation into damaged DNA was used as an indicator of DNA fragmentation. Lesion to normal ratios (LNRs) for [(123)I]IMP and [(125)I]IMZ were calculated. [(123)I]IMZ accumulation was preserved in several regions with impaired [(123)I]IMP accumulation. COX-2 expression was occasionally observed, whereas neither DNA fragmentation nor MAP-2 denaturation was detected in these regions. DNA fragmentation and impaired MAP-2 immunostaining were observed only in the regions with reduced LNRs for both tracers. The LNR for [(123)I]IMZ was significantly lower in regions with impaired MAP-2 immunostaining (0.120+/-0.152, P<0.0001), in regions positive for dUTP incorporation (0.488+/-0.166, P<0.0001) and in regions positive for COX-2 expression (0.626+/-0.186, P<0.001) than in histologically normal regions (0.784+/-0.213). Thus, neuronal DNA is still intact and cellular integrity is maintained in the ischaemic regions with preserved [(123)I]IMZ accumulation. The impairment of [(123)I]IMZ accumulation precedes DNA fragmentation and denaturation of cellular integrity. These results provide the molecular basis of [(123)I]IMZ distribution.

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

UNLABELLED: 1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. METHODS: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were 0.8. RESULTS: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001). CONCLUSION: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.