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Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with 89 Zr or 211 At as a theranostic target in pancreatic ductal adenocarcinoma. Methods: GPC1 mAb clone 01a033 was labeled with 89 Zr or 211 At with a deferoxamine or decaborane linker, respectively. The internalization ability of GPC1 mAb was evaluated by fluorescence conjugation using a confocal microscope. PANC-1 xenograft mice ( n = 6) were intravenously administered [ 89 Zr]GPC1 mAb (0.91 ± 0.10 MBq), and PET/CT scanning was performed for 7 d. Uptake specificity was confirmed through a comparative study using GPC1-positive (BxPC-3) and GPC1-negative (BxPC-3 GPC1-knockout) xenografts (each n = 3) and a blocking study. DNA double-strand breaks were evaluated using the γH2AX antibody. The antitumor effect was evaluated by administering [ 211 At]GPC1 mAb (∼100 kBq) to PANC-1 xenograft mice ( n = 10). Results: GPC1 mAb clone 01a033 showed increased internalization ratios over time. One day after administration, a high accumulation of [ 89 Zr]GPC1 mAb was observed in the PANC-1 xenograft (SUV max , 3.85 ± 0.10), which gradually decreased until day 7 (SUV max , 2.16 ± 0.30). The uptake in the BxPC-3 xenograft was significantly higher than in the BxPC-3 GPC1-knockout xenograft (SUV max , 4.66 ± 0.40 and 2.36 ± 0.36, respectively; P = 0.05). The uptake was significantly inhibited in the blocking group compared with the nonblocking group (percentage injected dose per gram, 7.3 ± 1.3 and 12.4 ± 3.0, respectively; P = 0.05). DNA double-strand breaks were observed by adding 150 kBq of [ 211 At]GPC1 and were significantly suppressed by the internalization inhibitor (dynasore), suggesting a substantial contribution of the internalization ability to the antitumor effect. Tumor growth suppression was observed in PANC-1 mice after the administration of [ 211 At]GPC1 mAb. Internalization inhibitors (prochlorperazine) significantly inhibited the therapeutic effect of [ 211 At]GPC1 mAb, suggesting an essential role in targeted α-therapy. Conclusion: [ 89 Zr]GPC1 mAb PET showed high tumoral uptake in the early phase after administration, and targeted α-therapy using [ 211 At]GPC1 mAb showed tumor growth suppression. GPC1 is a promising target for future applications for the precise diagnosis of pancreatic ductal adenocarcinoma and GPC1-targeted theranostics., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Fibroblast activation protein (FAP), which promotes tumor growth and progression, is overexpressed in cancer-associated fibroblasts of many human epithelial cancers. Because of its low expression in normal organs, FAP is an excellent target for theranostics. In this study, we used radionuclides with relatively long half-lives, 64 Cu (half-life, 12.7 h) and 225 Ac (half-life, 10 d), to label FAP inhibitors (FAPIs) in mice with human pancreatic cancer xenografts. Methods: Male nude mice (body weight, 22.5 ± 1.2 g) were subcutaneously injected with human pancreatic cancer cells (PANC-1, n = 12; MIA PaCa-2, n = 8). Tumor xenograft mice were investigated after the intravenous injection of 64 Cu-FAPI-04 (7.21 ± 0.46 MBq) by dynamic and delayed PET scans (2.5 h after injection). Static scans 1 h after the injection of 68 Ga-FAPI-04 (3.6 ± 1.4 MBq) were also acquired for comparisons using the same cohort of mice ( n = 8). Immunohistochemical staining was performed to confirm FAP expression in tumor xenografts using an FAP-α-antibody. For radioligand therapy, 225 Ac-FAPI-04 (34 kBq) was injected into PANC-1 xenograft mice ( n = 6). Tumor size was monitored and compared with that of control mice ( n = 6). Results: Dynamic imaging of 64 Cu-FAPI-04 showed rapid clearance through the kidneys and slow washout from tumors. Delayed PET imaging of 64 Cu-FAPI-04 showed mild uptake in tumors and relatively high uptake in the liver and intestine. Accumulation levels in the tumor or normal organs were significantly higher for 64 Cu-FAPI-04 than for 68 Ga-FAPI-04, except in the heart, and excretion in the urine was higher for 68 Ga-FAPI-04 than for 64 Cu-FAPI-04. Immunohistochemical staining revealed abundant FAP expression in the stroma of xenografts. 225 Ac-FAPI-04 injection showed significant tumor growth suppression in the PANC-1 xenograft mice, compared with the control mice, without a significant change in body weight. Conclusion: This proof-of-concept study showed that 64 Cu-FAPI-04 and 225 Ac-FAPI-04 could be used in theranostics for the treatment of FAP-expressing pancreatic cancer. α-therapy targeting FAP in the cancer stroma is effective and will contribute to the development of a new treatment strategy., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

PET radioligands with low molar activity (MA) may underestimate the quantity of the target of interest because of competitive binding of the target with unlabeled ligand. The aim of this study was to evaluate the change in the whole-body distribution of 18 F-PSMA-1007 targeting prostate-specific membrane antigen (PSMA) when solutions with different peptide concentrations are used. Methods: Mouse xenograft models of LNCaP (PSMA-positive prostate cancer) ( n = 18) were prepared and divided into 3 groups according to the peptide concentration injected: a high-MA group (1,013 ± 146 GBq/μmol; n = 6), a medium-MA group (100.7 ± 23.1 GBq/μmol; n = 6), and a low-MA group (10.80 ± 2.84 GBq/μmol; n = 6). Static PET scans were performed 1 h after injection (scan duration, 10 min). SUV mean in tumor and normal organs was compared by the multiple-comparison test. Immunohistochemical staining and Western blot analysis were performed to confirm expression of PSMA in tumor, salivary gland, and kidney. Results: The low-MA group (SUV mean , 1.12 ± 0.30) showed significantly lower uptake of 18 F-PSMA-1007 in tumor than did the high-MA group (1.97 ± 0.77) and the medium-MA group (1.81 ± 0.57). On the other hand, in salivary gland, both the low-MA group (SUV mean , 0.24 ± 0.04) and the medium-MA group (0.57 ± 0.08) showed significantly lower uptake than the high MA group (1.27 ± 0.28). The tumor-to-salivary gland SUV mean ratio was 1.73 ± 0.55 in the high-MA group, 3.16 ± 0.86 in the medium-MA group, and 4.78 ± 1.29 in the low-MA group. The immunohistochemical staining and Western blot analysis revealed significant overexpression of PSMA in tumor and low expression in salivary gland and kidney. Conclusion: A decrease in the MA level of the injected 18 F-PSMA-1007 solution resulted in decreased uptake in tumor and, to a greater degree, in normal salivary gland. Thus, there is a possibility of minimizing the adverse effects in salivary gland by setting an appropriate MA level in PSMA-targeting therapy., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

211 At is an α-emitter that has similar chemical properties to iodine and is used in targeted α-therapy. In the present study, we added ascorbic acid (AA) to 211 At solution to increase the radiochemical purity of astatide and evaluated its efficacy against differentiated thyroid cancer, which is characterized by the expression of sodium/iodide symporter (NIS). Methods: Crude 211 At solution (AA(-)) and 211 At solution treated with AA (AA(+)) were prepared. Uptake by the thyroid was compared between the 2 solutions in normal male Wistar rats ( n = 6). Cellular uptake in K1-NIS cells was analyzed under the AA(+) and AA(-) conditions. AA(+) was injected at 3 doses into K1-NIS xenograft mice: 1 MBq ( n = 6), 0.4 MBq ( n = 6), and 0.1 MBq ( n = 6), and vehicle was injected into control mice ( n = 6). The treatment effects were compared among the 4 groups. Results: Uptake by the thyroid was significantly enhanced in rats injected with the AA(+) as compared with those injected with AA(-). Cellular uptake analysis showed significantly increased uptake of 211 At by the K1-NIS cells under the AA(+) condition as compared with the AA(-) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of 211 At at 3 and 24 h after administration (22.5 ± 10.4 and 12.9 ± 6.8 percentage injected dose, respectively). Tumor growth was immediately inhibited in a dose-dependent manner after administration of 211 At. In the survival analysis, the 211 At groups (0.1, 0.4, and 1 MBq) showed significantly better survival than the control group. Conclusion: Uptake of 211 At was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using 211 At solution treated with AA. The method also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted α-therapy., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: Genetic or environmental influences on cerebral glucose metabolism are unknown. We attempted to reveal these influences in elderly twins by means of (18)F-FDG PET., Methods: (18)F-FDG uptake was studied in 40 monozygotic and 18 dizygotic volunteer twin pairs aged 30 y or over. We also created 18 control pairs by pairing age- and sex-matched genetically unrelated subjects from dizygotic and monozygotic pairs. SUV images of the brain were reconstructed and analyzed by voxel-based statistical analysis with automated region-of-interest setting. The (18)F-FDG uptake in each cerebral lobe was semiquantified by taking a ratio of SUVmean in each region of interest to whole-brain SUVaverage. We calculated an intraclass correlation coefficient of SUV ratio in each region of interest for monozygotic and dizygotic pairs. By comparing differences in coefficients between monozygotic and dizygotic pairs, genetic and environmental contributions were estimated., Results: The intraclass correlation coefficient in monozygotic pairs was significantly higher than that in dizygotic pairs in the parietal lobes bilaterally (P < 0.001) and in the left temporal lobe (P < 0.05) but was not significantly different in other lobes., Conclusion: The present study indicated that in the right and left parietal lobes and left temporal lobe, cerebral glucose metabolism is influenced more by genetics than by environment, whereas in other brain regions the influence of environment is dominant., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Unlabelled: PET with (15)O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the (15)O gas steady-state inhalation method for normal anesthetized rats., Methods: Eight normal male Sprague-Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by (15)O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm(3); frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with (15)O-CO(2) and (15)O-O(2) gases delivered through the radioactive gas stabilizer. CBV was measured by (15)O-CO gas inhalation and corrected for the intravascular hemoglobin-bound (15)O-O(2). Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images., Results: The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68-85) min. In both the (15)O-CO(2) and the (15)O-O(2) studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 ± 4.5 mL/100 mL/min; CMRO(2), 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% ± 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL., Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO(2) using the original steady-state inhalation method of (15)O-CO(2) and (15)O-O(2) gases and measurement of CBV using the (15)O-CO gas inhalation method in the brain of normal anesthetized rats.

Unlabelled: The linear correlation between (11)C-methionine PET and tumor cell density is not well conserved at the tumor border in glioma. A novel imaging analysis method, voxelwise (18)F-FDG-(11)C-methionine PET decoupling analysis (decoupling score), was evaluated to determine whether it could be used to quantitatively assess glioma cell infiltration in MRI-nonenhancing T2 hyperintense lesions., Methods: Data collection was performed in a prospective fashion. Fifty-four MRI-nonenhancing T2 hyperintense specimens were stereotactically obtained from 23 glioma patients by intraoperative navigation guidance. The decoupling score and tumor-to-normal tissue (T/N) ratio of (11)C-methionine PET were calculated at each location. Correlations between the tumor cell density at these lesions, decoupling score, and T/N ratio of (11)C-methionine PET were then evaluated., Results: Both the decoupling score and the T/N ratio showed a linear correlation with tumor cell density at these specimens (R(2) = 0.52 and 0.53, respectively). Use of the decoupling score (cutoff = 3.0) allowed the detection of specimens with a tumor cell density of more than 1,000/mm(2), with a sensitivity and specificity of 93.5% and 87.5%, respectively, whereas conventional (11)C-methionine PET (cutoff = 1.2 in T/N ratio) was able to detect with a sensitivity and specificity of 87.0% and 87.5%, respectively. Reconstructed images (decoupling map) using the decoupling score enabled the visualization of glioma lesions that were difficult to visualize by (11)C-methionine PET alone., Conclusion: The decoupling score showed better performance in detecting glioma cell infiltration than (11)C-methionine uptake alone, thus suggesting that (18)F-FDG-(11)C-methionine uptake decoupling analysis is a powerful imaging modality for assessing glioma invasion.

Unlabelled: Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess chemotherapeutic response metabolically and quantitatively. The aim of this study was to evaluate therapeutic response to neoadjuvant chemotherapy for locally advanced esophageal cancer, comparing PERCIST with the currently widely used response evaluation criteria in solid tumors (RECIST)., Methods: Fifty-one patients with locally advanced esophageal cancer who received neoadjuvant chemotherapy (5-fluorouracil, adriamycin, and cisplatin), followed by surgery were studied. Chemotherapeutic lesion responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methods. The PET/CT scans were obtained before chemotherapy and about 2 wk after completion of chemotherapy. Associations were statistically analyzed between survival (overall and disease-free survival) and clinicopathologic results (histology [well-, moderately, and poorly differentiated squamous cell carcinoma], lymphatic invasion, venous invasion, clinical stage, pathologic stage, resection level, reduction rate of tumor diameter, reduction rate of tumor uptake, chemotherapeutic responses in RECIST and PERCIST, and pathologic response)., Results: There was a significant difference in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P < 0.0001). Univariate analysis showed that lymphatic invasion, venous invasion, resection level, pathologic stage, and PERCIST were significant factors associated with disease-free or overall survival in this study. Although multivariate analysis demonstrated that venous invasion (disease-free survival: hazard ratio [HR] = 4.519, P = 0.002; overall survival: HR = 5.591, P = 0.003) and resection level (disease-free survival: HR = 11.078, P = 0.001) were the significant predictors, PERCIST was also significant in noninvasive therapy response assessment before surgery (disease-free survival: HR = 4.060, P = 0.025; overall survival: HR = 8.953, P = 0.034)., Conclusion: RECIST based on the anatomic size reduction rate did not demonstrate the correlation between therapeutic responses and prognosis in patients with esophageal cancer receiving neoadjuvant chemotherapy. However, PERCIST was found to be the strongest independent predictor of outcomes. Given the significance of noninvasive radiologic imaging in formulating clinical treatment strategies, PERCIST might be considered more suitable for evaluation of chemotherapeutic response to esophageal cancer than RECIST.

Unlabelled: (123)I-Iomazenil brain SPECT has been used for the detection of epileptogenic foci, especially when surgical intervention is considered. Although epileptogenic foci exhibit a decrease in (123)I-iomazenil accumulation, normal cerebral cortices often exhibit similar findings because of thin cortical ribbons, gray matter atrophy, or pathologic brain structures. In the present study, we created (123)I-iomazenil SPECT images corrected for gray matter volume using MRI and tested whether the detectability of the epileptogenic foci improved., Methods: Seven patients (1 male patient and 6 female patients; mean age +/- SD, 34 +/- 17 y) with intractable epilepsy were surgically treated by resecting the cerebral cortex after surface electroencephalography. Histopathologic examination of the resected specimens and a good outcome after surgery indicated that the resected lesions were epileptogenic foci. These patients underwent (123)I-iomazenil SPECT and 3-dimensional T1-weighted MRI examinations before their operations. Each SPECT image was coregistered to the corresponding MR image, and its partial-volume effect (PVE) was corrected on a voxel-by-voxel basis with a smoothed gray matter distribution image. Four nuclear medicine physicians visually evaluated the (123)I-iomazenil SPECT images with and without the PVE correction. The SPECT count ratio of the suspected focus to the contralateral cerebral cortex was evaluated as an asymmetry index (%) based on the volume of interest., Results: The sensitivity, specificity, and accuracy of focus detection by visual assessment were higher after PVE correction (88%, 99%, and 98%, respectively) than before correction (50%, 92%, and 87%, respectively). The mean asymmetry index for the surgically resected lesions was significantly higher on the PVE-corrected SPECT images (22%) than on the PVE-uncorrected ones (16%) (P = 0.006)., Conclusion: MRI-based PVE correction for (123)I-iomazenil brain SPECT improves the sensitivity and specificity of the detection of cortical epileptogenic foci in patients with intractable epilepsy.

Unlabelled: Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET., Methods: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET., Results: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent., Conclusion: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.

Unlabelled: We recently proposed a simplified technique for measuring regional cerebral blood flow (rCBF) using the [123I]N-isopropyl-p-iodoamphetamine (IMP) autoradiographic (ARG) method with SPECT (the IMP-ARG method). We examined normal values of rCBF and the reproducibility and sensitivity to hypoperfusion in stroke patients using this method., Methods: By using a standard arterial input, a single static scan, a fixed distribution volume (Vd) and one-point arterial blood sampling, we measured rCBF in 39 normal volunteers (19 men and 20 women; mean ages 61 +/- 11 yr for the men and 60 +/- 12 yr for the women). Eighteen neurologically stable patients with prior stroke (mean age = 65 +/- 11 yr) were studied twice at a mean interval of 97 days. In 16 patients (7 men and 9 women, mean age = 63 +/- 5 yr) with subarachnoid hemorrhage, rCBF was measured 1-2 wk after onset. Cerebral vasospasm was evaluated by repeated angiography. The mean rCBF in the vasospastic area was compared with that in a nonvasospastic area., Results: The mean rCBFs of the cerebral cortex and centrum semiovale in the volunteers were 33.0 +/- 5.1 ml/100 g/min and 25.0 +/- 4.5 ml/100 g/min, respectively. There was no age-dependent change in rCBF, but the women showed significantly higher cortical rCBF than the men (p < 0.05). In the stroke patients, the whole-brain CBF values showed high reproducibility, with high correlations between those obtained at the first and second studies (y = -3.5 + 1.03x; r = 0.90; p < 0.001). In the subarachnoid hemorrhage patients, the vasospastic area showed significantly lower rCBF than the normal cortical rCBF (p < 0.01) and the nonvasospastic area (p < 0.01). Brain regions with rCBF levels below 20 ml/100 g/min showed infarction on the follow-up CT scan., Conclusion: The IMP-ARG method is reproducible, sensitive to hypoperfusion and feasible for the quantitative evaluation of rCBF in routine clinical practice.

Unlabelled: Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain distribution have been reported when brain tissue is supplied by excess blood flow. We evaluated changes in 99mTc-ECD brain activity in the opposing pathological state, in which cerebral blood flow (CBF) is more profoundly impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity with CBF and metabolism to investigate the dominant regulating factor on 99mTc-ECD distribution., Methods: Twelve patients with unilateral intracranial steno-occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT. Relative 99mTc-ECD activities and the retention ratio of the affected and unaffected cortices were compared with CBF and oxygen metabolism obtained by PET. Change in the relationships until 1 hr after tracer injection were also analyzed., Results: Relative 99mTc-ECD activity was significantly correlated with CBF, and the highest correlation was obtained for the first minute of imaging (r = 0.674, p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF decreased, whereas higher correlation was observed with the parameter of oxygen metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were dependent on changes in oxygen metabolism, and the retention ratio for the high oxygen extraction fraction (OEF) area was the same as that for the normal OEF area., Conclusion: In addition to CBF, brain distribution on 99mTc-ECD SPECT images is affected by brain metabolism, especially on delayed images after injection. The degree of discrepancy between CBF and metabolism should be considered when interpreting images of the misery perfusion state.

Unlabelled: We evaluated whether PET with L-methyl-11C-methionine (11C-methionine) was clinically useful in distinguishing neoplastic from non-neoplastic intracerebral hematoma., Methods: We examined eight patients with neoplastic (n = 4) or non-neoplastic (n = 4) intracerebral hematomas between 5 and 68 days after the bleeding episode using PET with 11C-methionine (Met-PET)., Results: Carbon-11-methionine accumulated in the area surrounding the hematoma in both groups, except in one patient with an acute hypertensive hematoma. Between 22 and 45 days after the ictus, non-neoplastic hematomas showed increased 11C-methionine accumulation largely in accordance with the contrast-enhanced areas on CT or MR images; whereas between 14 and 68 days after bleeding, neoplastic hematomas showed increased 11C-methionine accumulation that extended beyond the contrast-enhanced areas on CT or MR images. The intensity of 11C-methionine accumulation in tumor tissue was greater than that in non-neoplastic hematomas., Conclusion: Preliminary results suggest that Met-PET can distinguish neoplastic from non-neoplastic hematomas on the basis of differences in lesion extent compared with CT or MR findings.

Unlabelled: This study evaluates ischemic damage to central benzodiazepine (BZD) receptor binding in the brain with [123]iomazenil SPECT in relation to CT hypodense lesions and blood flow abnormalities., Methods: Nine patients with middle cerebral artery territory infarction were studied. Iomazenil images obtained 180 min postinjection were analyzed for BZD receptor binding. The cortical infraction, visualized as CT hypodense area on CT, the peri-infarct area, visualized as normodensity surrounding the infarction on CT, the intrahemispheric remote area and the cerebellum were analyzed by taking the ratio of the lesion to contralateral mirror region (L/C ratio). CT during the chronic stage and perfusion images obtained during the smallest time difference between the two studies were used for comparative analysis., Results: The mean L/C ratio of iomazenil uptake was 0.53 +/&#95; 0.08, 0.79 +/- 0.07, 0.98 +/- 0.03 and 1.00 +/- 0.04 in the infarct, peri-infarct and remote areas and the cerebellum, respectively. The infarct and peri-infarct areas showed significant decrease compared with unity. The corresponding mean L/C ratio for blood flow was 0.52 +/- 0.08, 0.73 +/- 0.07, 0.83 +/- 0.09, and 0.80 +/- 0.07, respectively. In all areas, the ratios were significantly decreased compared with unity. There was significant difference between the L/C ratio for blood flow and iomazenil in the remote area and the cerebellum., Conclusion: Iodine-123-iomazenil SPECT imaging may provide new information on ischemic damage to the brain, particularly neurons.

Unlabelled: Technetium-99m-HMPAO can be used to evaluate abnormal brain perfusion in the hyperacute stage of stroke., Methods: We investigated cerebral blood flow using 99mTc-HMPAO SPECT in 31 patients within 6 hr after the onset of cerebral infarction and analyzed the relationship between abnormal perfusion and morphological changes on follow-up CT scans. Patients were classified into an infarct group and a noninfarct group, and the lesions on SPECT images were divided into infarct and peri-infarct regions., Results: Among a total of 30 infarct regions, three lesions studied at 1.5, 2.5 and 5 hr after the ictus showed local hyperperfusion suggestive of early postischemic hyperemia, while the other 27 lesions demonstrated local hypoperfusion. All of the peri-infarct regions showed moderate hypoperfusion. The noninfarct group consisted of five patients, four of whom showed no perfusion abnormalities. The lesion-to-contralateral radioactivity ratios for the infarct and peri-infarct regions were respectively 0.48 +/- 0.14 and 0.75 +/- 0.10 in the patients with hypoperfusion, while the right-to-left ratio in the noninfarct group was 0.97 +/- 0.10., Conclusion: This SPECT study of cerebral blood flow demonstrates that local hyperperfusion occurs in some infarcts even within 6 hr of onset and that infarcted and morphological viable brain can be distinguished by a lesion-to-contralateral radioactivity ratio of 0.6 within this time range.

A 29-yr-old woman was studied for 1 yr after acute carbon monoxide intoxication following an attempted suicide by inhalation of automobile exhaust fumes. The patient demonstrated impaired responsiveness to stimuli without any specific neurological deficits for 1 yr after carbon monoxide intoxication. Repeated brain magnetic resonance imaging consistently displayed only bilateral globus pallidus lesions, but no lesions in either deep white matter or cerebral cortex. Position emission tomography measurements of regional cerebral blood flow, and glucose utilization rate were made in this patient at 6 mo and 1 yr following carbon monoxide intoxication. Impairment of both blood flow and glucose metabolism were found not only in the basal ganglia but also in morphologically normal frontal cortex. The decrease in glucose utilization in the frontal cortex was greater than that in the basal ganglia. During the period of 6 mo to 1 yr, blood flow and glucose metabolism in the basal ganglia recovered to the normal range. In the frontal cortex, however, blood flow and glucose metabolism remained approximately 20% lower than the normal mean values. This prolonged dysfunction in the frontal cortex may therefore be responsible for the impaired responsiveness of the subject.