Seigo Kinuya

Standardization of metaiodobenzylguanidine heart to mediastinum ratio using a calibration phantom: effects of correction on normal databases and a multicentre study

PurposeThis study was performed to demonstrate that the results obtained with a calibration phantom could be used as a tool for standardizing measurement of heart to mediastinum (H/M) ratio in cardiac metaiodobenzylguanidine (MIBG) imaging.MethodsImages of the phantom containing 123I-MIBG were acquired on the cameras in 10 hospitals (11 camera types) to determine the relationship between H/M ratios using different collimators: low-energy (LE) and medium-energy (ME)/low–medium-energy (LME) collimators. The effect of standardization on the ME-comparable H/M ratio was examined in two settings: a Japanese standard MIBG database (n = 62) and multicentre studies (n = 49). In a multicentre study, probable Alzheimer’s disease (AD, n = 18) and probable dementia with Lewy bodies (DLB, n = 31) were studied and standardized by the calibration phantom method.ResultsLinear regression equations between LE and ME collimators were obtained for the phantom study in all institutions. When the H/M ratio with an LE collimator was corrected based upon the calibration phantom, the corrected values were comparable to those obtained using ME collimators. The standard database also exhibited a normal distribution after standardization as determined by skewness and goodness-of-fit test. A mixture of the populations by LE and ME collimators showed significant separation of AD and DLB groups (F ratio = 24.9 for the late H/M), but the corrected values resulted in higher F ratios for both early and late H/M (F ratio = 34.9 for the late H/M).ConclusionStandardization of H/M ratios by the heart-chest calibration phantom method is feasible among different collimator types. This method could be practically used for multicentre comparison of H/M ratios.

Iodine-123 Metaiodobenzylguanidine Imaging and Carbon-11 Hydroxyephedrine Positron Emission Tomography Compared in Patients With Left Ventricular Dysfunction

Background—Although both 123I-metaiodobenzylguanidine (123I-MIBG) imaging and 11C-hydroxyephedrine (11C-HED) positron emission tomography (PET) are used for assessing cardiac sympathetic innervation, their relationship remains unknown. The aims were to determine whether 123I-MIBG parameters such as heart-to-mediastinum ratio (H/M) are associated with quantitative measures by 11C-HED PET and to compare image quality, defect size, and location between 123I-MIBG single-photon emission computed tomography (SPECT) and 11C-HED PET. Methods and Results—Twenty-one patients (mean left ventricular ejection fraction, 39±15%) underwent 123I-MIBG imaging and 11C-HED PET. Early (15-minute), late (3-hour) H/M, and washout rate (WR) were calculated for 123I-MIBG. Myocardial retention and WR was calculated for 11C-HED. Using a polar map approach, defect was defined as the area with relative activity <60% of the maximum. Both the early (r=0.76) and late (r=0.84) 123I-MIBG H/M were correlated with 11C-HED retention. 123I-MIBG WR was correlated with 11C-HED WR (r=0.57). Defect size could not be measured in 3 patients because of poor quality 123I-MIBG SPECT, whereas 11C-HED defect was measurable in all patients. Although defect size measured by early or late 123I-MIBG SPECT was closely correlated with that by 11C-HED PET (early: r=0.94; late: r=0.88), the late 123I-MIBG overestimated defect size particularly in the inferior and septal regions. Conclusions—123I-MIBG H/M gives a reliable estimate of cardiac sympathetic innervation as measured by 11C-HED PET. Furthermore, despite the close correlation in defect size, 11C-HED PET appears to be more suitable for assessing regional abnormalities than does 123I-MIBG SPECT.

Comparison of 18F-FDG PET and Optimized Voxel-Based Morphometry for Detection of Alzheimer's Disease: Aging Effect on Diagnostic Performance

The aim of this study was to compare optimized voxel-based morphometry (VBM) and 18F-FDG PET for discrimination between patients with Alzheimers disease (AD) and healthy subjects in relation to age. Methods: The study population consisted of 2 groups; the first group (27 AD patients and 40 control subjects) was used to determine the locations of significant abnormalities for both PET and VBM using statistical parametric mapping, and the second group (34 AD patients and 50 control subjects) was used to compare the diagnostic performance of PET and VBM. In the second group, a z-score map for PET or VBM of each subject was obtained by comparison with the mean and SD of PET or gray-matter MR images of the control subjects. Receiver-operating-characteristic (ROC) curve analysis was then performed to compare the diagnostic performance between PET and VBM. Furthermore, group 2 was divided into the early- and late-onset subgroups, and ROC analysis was performed for each subgroup. Results: In the first group, VBM revealed a significant decrease in gray-matter concentration in the hippocampus complex in AD, whereas PET showed a significant reduction in 18F-FDG uptake in the posterior cingulate and parietotemporal lobe. The diagnostic performance of PET (0.988 ± 0.008; mean ± SE), as measured by the area under the ROC curve, was higher than that of VBM with (0.782 ± 0.059) or without (0.832 ± 0.049) modulation. PET yielded a sensitivity, specificity, and overall accuracy of 100%, 92%, and 95%, respectively, whereas for VBM the sensitivity, specificity, and accuracy were 74%, 92%, and 85%. Modulation for the VBM did not improve these values (56%, 94%, and 79%, respectively). When the early- and late-onset subjects were analyzed separately, the superiority of 18F-FDG PET was significant only in the early-onset subgroup. Conclusion: The present study indicates that the detection of metabolic alteration by 18F-FDG PET yields a better diagnostic performance for the discrimination between AD patients and healthy control subjects than does the morphologic approach by VBM, particularly in the early-onset subjects.

Comparison of diagnostic value of I-123 MIBG and high-dose I-131 MIBG scintigraphy including incremental value of SPECT/CT over planar image in patients with malignant pheochromocytoma/paraganglioma and neuroblastoma.

Purpose: To compare lesion detectability of I-123 MIBG scintigraphy with that of high-dose I-131 MIBG and to evaluate incremental benefit of SPECT/CT over planar image for the detection and localization of the lesions in patients with I-131 MIBG therapy for malignant pheochromocytoma/paraganglioma and neuroblastoma. Materials and Methods: We retrospectively investigated 16 patients with malignant pheochromocytoma/paraganglioma and neuroblastoma, who were referred for I-131 MIBG therapy. We investigated the lesion detectability in 10 pairs of I-123 and high-dose I-131 MIBG studies of the same patient, obtained within 2 weeks. In 31 studies of I-123 MIBG scintigraphy in 16 patients and 17 studies of high-dose I-131 MIBG scintigraphy in 12 patients, we compared planar and SPECT/CT images for the lesion detectability and localization. Results: The number of lesions detected by I-123 MIBG planer image and SPECT/CT and high-dose planer I-131 MIBG and SPECT/CT were 3.0 and 3.7, 7.3 and 7.7 per study, respectively. SPECT/CT images provided additional diagnostic information over planar images in 25 studies (81%) of 12 patients (75%) in I-123 MIBG scintigraphy and in 9 studies (53%) of 9 patients (75%) in high-dose I-131 MIBG scintigraphy. Conclusion: Post-therapy high-dose I-131 MIBG scintigraphy is superior to I-123 MIBG scintigraphy in lesion detectability even in comparison with I-123 MIBG SPECT/CT images and high-dose I-131 MIBG planar images in patients with malignant neuroendocrine tumors. SPECT/CT images are helpful for accurate identification of anatomic localization compared with planar images.

Evaluation of suspected malignant pulmonary lesions with 201Tl single photon emission computed tomography.

201Tl single photon emission computed tomography (SPECT) was evaluated in 170 patients suspected of having a malignant pulmonary lesion greater than 20 mm in diameter on the surgical specimen. Delayed SPECT (at 3 h after injection) visualized all of the 147 malignant pulmonary lesions and 16 of the 23 (69.6%) benign pulmonary lesions, and generally exhibited the lesion more clearly than the early SPECT images (at 15 min after injection). There was no significant difference in delayed ratio (uptake ratio of the lesion to the normal lung on delayed scan) among the various histological groups except between the adenocarcinoma and large cell carcinoma groups (P < 0.05), and no difference was noted between the malignant and benign lesions. However, in retention index (degree of retention in the lesion) a significant difference was noted between the malignant and benign lesions (P < 0.01), although there was no significant difference in this index among malignant different histology groups. These results indicate that this method is useful for visualizing malignant pulmonary lesions greater than 20 mm in diameter to exclude the possibility of malignancy in the lesions when no abnormal 201Tl accumulation is observed. When the lesion shows abnormal 201Tl accumulation, the retention index seems to help differentiate malignant from benign lesions.

Effect of Postconditioning on Myocardial 99mTc-Annexin-V Uptake: Comparison with Ischemic Preconditioning and Caspase Inhibitor Treatment

99mTc-Annexin-V imaging has been proved to be feasible to detect phosphatidylserine, which externalizes on the outer cell membrane early in the process of apoptosis. To determine whether postconditioning suppresses myocardial cell damage or apoptosis, we evaluated the intensity and distribution of 99mTc-annexin-V uptake after postconditioning in a rat model of ischemia and reperfusion and compared the effect to that of ischemic preconditioning and pretreatment with caspase inhibitor. Methods: In control rats (n = 13), after thoracotomy the left coronary artery was occluded for 20 min followed by reperfusion for 30 or 90 min and injection of 99mTc-annexin-V (80–150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just beyond the left coronary artery reocclusion, and the rats were sacrificed 1 min later. In the groups of rats with various interventions, postconditioning (n = 11) was performed just after the reperfusion, and preconditioning (n = 11) and caspase inhibitor treatment (n = 11) were performed before ischemia. Dual-tracer autoradiography was performed to assess 99mTc-annexin-V uptake and area at risk. Results: In all control rats, intense 99mTc-annexin-V uptake was observed in the area at risk (uptake ratios at 30 or 90 min after reperfusion, 4.15 ± 1.89 and 3.70 ± 1.41, respectively). Postconditioning suppressed 99mTc-annexin-V uptake (uptake ratios at 30 or 90 min after reperfusion, 2.09 ± 0.56, P < 0.05, and 1.88 ± 0.69, P < 0.05, respectively). Preconditioning also suppressed uptake (uptake ratios at 30 and 90 min after reperfusion, 1.17 ± 0.29, P < 0.005, and 1.33 ± 0.74, P < 0.01, respectively), as did caspase inhibitor (uptake ratios at 30 and 90 min after reperfusion, 2.08 ± 0.50, P < 0.05, and 1.27 ± 0.24, P < 0.005, respectively). In all interventions, the percentage of cells positive on deoxyuride-5′-triphosphate biotin nick end labeling and histologic changes with myocardial cell degeneration and cell infiltrations were suppressed markedly. Conclusion: These data indicate that 99mTc-annexin-V imaging may be a way to monitor myocardial injury and its response to novel therapeutic interventions including postconditioning, preconditioning, and antiapoptotic therapy.

Reversible cerebral hypoperfusion observed with Tc-99m HMPAO SPECT in reversible dementia caused by hypothyroidism

A 69-year-old man had hypothyroid dementia as a result of I-131 therapy and an overdose of methimazole. Tc-99m HMPAO SPECT revealed diffuse cerebral hypoperfusion. The findings of brain SPECT normalized with the disappearance of symptoms and a return to the euthyroid state. There was a 25% or 26% reduction of the mean cerebral blood flow during dementia. This may be the first report in which SPECT brain imaging revealed reversible hypoperfusion associated with reversible hypothyroid dementia.

Esophageal hypomotility in systemic sclerosis: close relationship with pulmonary involvement.

Purpose: Esophageal motility was assessed in patients with systemic selerosis (SSc) by scintigraphy and compared with (i) extent of scleroderma, (ii) duration of disease, (iii) index of antitopoisomerase I antibody (topo I), and (iv) pulmonary involvement.Methods: A multiple-swallow test was performed in 47 patients with SSc in the supine position with99mTc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve.Results: Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p<0.05). There was no correlation between the RRs and the duration of disease. Patients with positive topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p<0.05). Patients with reduced % diffusion capacity for carbon monoxide (%DLCO) had higher RRs thans those with normal %DLCO (40.5% vs. 19.6%; p=0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal % VC (54.6% vs. 25.0%; p<0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p<0.00005).Conclusion: Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis.

Efficacy, toxicity and mode of interaction of combination radioimmunotherapy with 5-fluorouracil in colon cancer xenografts

Purpose:The feasibility of radioimmunotherapy (RAIT) combined with 5-fluorouracil (5-FU) was examined in colon cancer xenografts. The mode of interaction of the two treatments was also investigated. Methods: Mice bearing human colon cancer were treated with a combination of 4.63 MBq (L-RAIT) or 9.25 MBq (H-RAIT) 131I-A7, an IgG1 against 45-kDa glycoprotein, and 5-FU at a dose of 30 mg kg−1 day−1 for 5 days. Myelotoxicity was monitored by blood cell counts and intestinal toxicity was assessed by the dosimetry. The results were compared with those of a single-modality therapy. Results: The combination of 5-FU with H-RAIT enhanced the antitumor effect, improving the tumor quadrupling time from 25.3 ± 9.59 days to 31.3 ± 8.32 days (P < 0.05) and inducing tumor regression in 7 out of 10 mice, compared to 3 out of 9 mice treated with H-RAIT alone. The efficacy of L-RAIT was also improved by the combination. Analysis of the dose/response relationship showed an additive interaction of the two modalities. The combination of 5-FU with RAIT induced slightly more severe myelotoxicity than a single-modality treatment, but blood cell counts recovered similarly. Dose estimation suggested that RAIT does not increase the intestinal toxicity of 5-FU. Conclusion: The combination of two modalities would be feasible for the treatment of colon cancer, increasing antitumor effect with minor effect on toxicity.

Dynamic Expression of Tenascin-C After Myocardial Ischemia and Reperfusion: Assessment by 125I-Anti–Tenascin-C Antibody Imaging

Tenascin-C, an extracellular matrix glycoprotein, appears only in the early stages of embryonic development. It is not normally expressed in the adult heart but does reappear transiently in distinct areas in association with active tissue remodeling. The aim of this study was to explore serial changes in the expression of tenascin-C after myocardial ischemia and reperfusion, using 125I-labeled anti–tenascin-C antibody (125I-TNC-Ab) in a rat model of acute ischemia and reperfusion. Methods: The left coronary artery was occluded for 20 or 30 min, followed by reperfusion for 1, 3, or 7 d in rats with 20 min of ischemia and for 1, 3, 7, 14, or 28 d in rats with 30 min of ischemia. At the time of the study, 125I-TNC-Ab (1.0–2.5 MBq) was injected. Three to 5 h later, to verify the area at risk, 99mTc-methoxyisobutylisonitrile (100–200 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess 125I-TNC-Ab uptake and the area at risk. Results: In rats with 20 min of ischemia, 125I-TNC-Ab uptake peaked at 3 d after reperfusion, followed by faint uptake after 7 d (uptake ratios at 1, 3, and 7 d after reperfusion were 1.81 ± 0.53, 2.46 ± 0.79, and 1.23 ± 0.17, respectively [P < 0.05 vs. 3 d]). In rats with 30 min of ischemia, uptake was high at 1 and 3 d after reperfusion (2.99 ± 0.90 and 2.71 ± 0.80, respectively), decreased at 7 and 14 d (1.94 ± 0.23 and 2.06 ± 0.37, respectively), and was weak at 28 d (1.47 ± 0.27, P < 0.005 vs. 1 d, P < 0.05 vs. 3 d). Conclusion: These data indicate that 125I-TNC-Ab imaging may be a way to monitor myocardial injury and its repair process after ischemia and reperfusion by visualizing tenascin-C expression.