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Pleomorphic xanthoastrocytoma (PXA) is a rare glial tumor, however, its histological differentiation from high-grade gliomas is often difficult. Molecular characteristics may contribute to a better diagnostic discrimination. Prognostic factors of PXA are also important but few relevant reports have been published. This study investigated the molecular features and prognostic factors of PXAs. Seven university hospitals participated in this study by providing retrospective clinical data and tumor samples of PXA cases between 1993 and 2014. Tumor samples were analyzed for immunohistochemical (IHC) neuronal and glial markers along with Ki67. The status of the BRAF and TERT promoter (TERTp) mutation was also evaluated using the same samples, followed by feature extraction of PXA and survival analyses. In all, 19 primary cases (17 PXA and 2 anaplastic PXA) were included. IHC examination revealed the stable staining of nestin and the close association of synaptophysin to NFP. Of the PXA cases, 57% had the BRAF mutation and only 7% had the TERTp mutation. On univariate analysis, age (≥60 years), preoperative Karnofsky performance status (KPS) (≤80%), and marked peritumoral edema were significantly associated with progression-free survival (PFS). No independent factor was indicated by the multivariate analysis. In conclusion, PXA was characterized by positive nestin staining and a few TERTp mutations. The neuronal differential marker and BRAF status may help in diagnosis. Patient age, preoperative KPS, and marked perifocal edema were associated with PFS. The present study is limited because of small number of cases and its retrospective nature. Further clinical study is needed.

Carmustine wafers (CW) were approved in Japan for newly diagnosed and recurrent malignant gliomas during 2013. The ventricle is often opened during surgery to achieve maximum resection. While not generally recommended in such situations, CW might be safely achieved by occluding an opened ventricle using gelform or collagen sheets. However, whether CW implantation actually confers a survival benefit for patients who undergo surgery with an open ventricle to treat glioblastoma remains unclear. Clinical, imaging, and survival data were collected in this multicenter retrospective study of 122 consecutive patients with newly diagnosed glioblastoma to determine adverse events and efficacy. Overall, 54 adverse events of all grades developed in 35 (28.6%) patients, with the most common being new seizures (16%). Adverse events did not significantly differ between patients with opened and closed ventricles during surgery. The 10- and 21.7-month, median, progression-free (PFS) and overall survival (OS), respectively did not significantly differ according to resection rates. However, median PFS and OS were significantly longer among patients with closed, than open ventricles (12.8 vs. 7.4 months; p = 0.0039 and 26.9 vs. 18.6 months; p = 0.011, respectively). Implanting CW into the resection cavity during concomitant radiochemotherapy with temozolomide seems to yield better survival rates without increased adverse events. Occlusion of the ventricular opening during surgery might be safe for CW implantation, but less so for treating patients with newly diagnosed glioblastoma.

Introduction: We examined whether the amino acid PET tracers, trans-1-amino-3-(18)F-fluorocyclobutanecarboxylic acid (anti-(18)F-FACBC) and (11)C-methyl-l-methionine ((11)C-Met), are suitable for detecting early responses to combination therapies including temozolomide (TMZ), interferon-β (IFN), and bevacizumab (Bev) in glioblastoma., Methods: Human glioblastoma U87MG (U87) cells were incubated with low dose TMZ to induce chemoresistance. Both trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) uptake were quantified using triple-label accumulation assays to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation) in vitro. U87 and U87R (TMZ-resistant subculture) cells were inoculated into the right and left basal ganglia, respectively, of F344/N-rnu rats. The efficacy of single-agent (TMZ, Bev) and combination therapy (TMZ/IFN, TMZ/Bev, TMZ/IFN/Bev) was examined in orthotopic gliomas using MRI, Evans blue extravasation, anti-(14)C-FACBC, and (3)H-Met autoradiography, and MIB-1 immunostaining., Results: TMZ treatment decreased (3)H-TdR accumulation and the volume distribution of anti-(14)C-FACBC and (3)H-Met in U87 but not U87R cells. TMZ/IFN combination therapy significantly decreased these parameters in U87R cells; however, Bev had no additional effect in vitro. In vivo, U87R-derived gliomas were observed as equivocal tumors on MRI and T2-high intensity lesions. Bev treatment, either alone or in combination, markedly decreased U87 enhancing lesions. By contrast, autoradiographic images using anti-(14)C-FACBC and (3)H-Met clearly delineated tumor extent, which spread widely beyond T2-high intensity lesions and enhancing lesions. TMZ therapy significantly decreased tracer accumulation and proliferation of U87- but not U87R-derived tumors. TMZ/IFN combination treatment significantly decreased these parameters in U87R tumors, which were further reduced (in both tumor types) by Bev addition. Tracer uptake correlated with the MIB-1 proliferation index. However, MRI was unsuitable for tumor delineation and assessment of Bev treatment response., Conclusions: Triple-agent therapy (TMZ/IFN/Bev) was effective against even TMZ-resistant glioblastomas. PET with amino acid tracers provides useful information on the early response of glioblastomas to single-agent and combination therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rapid immunohistochemistry (R-IHC) can contribute to the intraoperative diagnosis of central nervous system (CNS) tumors. We have recently developed a new IHC method based on an alternating current electric field to facilitate the antigen-antibody reaction. To ensure the requirement of R-IHC for intraoperative diagnosis, 183 cases of CNS tumors were reviewed regarding the accuracy rate of diagnosis without R-IHC. The diagnostic accuracy was 90.7 % (166/183 cases) [corrected] in which definitive diagnoses were not provided in 17 cases because of the failure of glioma grading and differential diagnosis of lymphoma and glioma. To establish the clinicopathological application, R-IHC for frozen specimens was compared with standard IHC for permanent specimens. 33 gliomas were analyzed, and the Ki-67/MIB-1 indices of frozen specimens by R-IHC were consistent with the grade and statistically correlated with those of permanent specimens. Thus, R-IHC provided supportive information to determine the grade of glioma. For discrimination between glioma and lymphoma, R-IHC was able to provide clear results of CD20 and Ki-67/MIB-1 in four frozen specimens of CNS lymphoma as well as standard IHC. We conclude that the R-IHC for frozen specimens can provide important information for intraoperative diagnosis of CNS tumors.

Age is one of the most important prognostic factors in glioblastoma patients, but no standard treatment has been established for elderly patients with this condition. We therefore conducted a retrospective cohort study to evaluate treatment regimens and outcomes in elderly glioblastoma patients. The study population consisted of 79 glioblastoma patients aged ≥ 76 years (median age 78.0 years; 34 men and 45 women). The median preoperative Karnofsky performance status (KPS) score was 60. Surgical procedures were classified as biopsy (31 patients, 39.2 %), <95 % resection of the tumor (21 patients, 26.9 %), and ≥ 95 % resection of the tumor (26 patients, 33.3 %). Sixty-seven patients (81.0 %) received radiotherapy and 45 patients (57.0 %) received chemotherapy. The median overall progression-free survival time was 6.8 months, and the median overall survival time was 9.8 months. Patients aged ≥ 78 years were significantly less likely to receive radiotherapy (p = 0.004). Patients with a postoperative KPS score of ≥ 60 were significantly more likely to receive maintenance chemotherapy (p = 0.008). Multivariate analyses identified two independent prognostic factors: postoperative KPS score ≥ 60 (hazard ratio [HR] = 0.531, 95 % confidence interval [CI] 0.315-0.894, p = 0.017) and temozolomide therapy (HR = 0.442, 95 % CI 0.25-0.784, p < 0.001).The findings of this study suggest that postoperative KPS score is an important prognostic factor for glioblastoma patients aged ≥ 76 years, and that these patients may benefit from temozolomide therapy.

Introduction: Amino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo., Methods: C6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated a significantly greater surviving fraction in the TMZ-resistant subline (C6R) than in drug-naive cells (C6). The anti-(14)C-FACBC and (3)H-Met uptakes were quantified using a triple-label accumulation assay to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation rate) in tumor cells. C6 and C6R cells were inoculated into the right and left basal ganglia, respectively, of rats. Efficacy of TMZ against the orthotopic gliomas was analyzed by MRI, Evans blue extravasation, anti-(14)C-FACBC and (3)H-Met autoradiography, and MIB-5 proliferation index., Results: The (3)H-TdR accumulation rate and amino acid tracer (anti-(14)C-FACBC and (3)H-Met) uptake significantly decreased 48 and 72 h, respectively, after TMZ treatment in C6 but not C6R cells. Anti-(14)C-FACBC uptake correlated significantly with (3)H-Met uptake and the (3)H-TdR accumulation rate. In the intracerebral glioma model, anti-(14)C-FACBC and (3)H-Met autoradiography clearly delineated the tumor extent, which spread well beyond the high-T2-intensity and enhancing lesions visible on MRI and Evans blue extravasation. TMZ significantly decreased anti-(14)C-FACBC and (3)H-Met uptake and the MIB-5 index of C6 but not C6R tumors. TMZ inhibited tracer uptake and tumor proliferation before morphological changes on MRI., Conclusions: Anti-(14)C-FACBC, like (3)H-Met, was more sensitive than post-contrast T1-weighted MRI for detecting tumor extent and early tumor response to TMZ treatment. Anti-(18)F-FACBC should be a sensitive and precise imaging biomarker for tumor extent visualization and response assessment in glioma patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Gliomatosis cerebri is a diffuse growth pattern of glioma consisting of exceptionally extensive infiltration of at least three cerebral lobes. We report a case of histologically confirmed glioblastoma multiforme in the cerebellar vermis which occurred 9 years after treatment for gliomatosis cerebri. A 33-year-old woman presented to our department for evaluation of visual disturbance. T2-weighted magnetic resonance (MR) imaging revealed hyperintense lesions in the bilateral frontal and parietal lobes. Histological examination of biopsy specimens from the left frontal lobe lesion demonstrated diffuse infiltration of glial neoplastic cells with preservation of the underlying cytoarchitecture, leading to the diagnosis of gliomatosis cerebri. She received 60 Gy hyperfractionated irradiation to the whole brain, and the lesion responded partially. The patient remained stable for 4 years, but T2-weighted MR imaging 5 years after the initial treatment showed enlargement of the hyperintense area. She received nimustine hydrochloride chemotherapy, and again partial response was observed. However. T1-weighted MR imaging after administration of gadolinium-diethylenetriaminepenta-acetic acid detected enhanced lesions in the cerebellar vermis, cerebellar hemisphere, and left posterior limb of the internal capsule 9 years after the initial treatment, although no abnormal findings were observed on initial and follow-up MR imaging. She underwent subtotal removal of the lesion in the cerebellar vermis. The surgical specimens were characterized by dense proliferation of atypical tumor cells with scattered mitosis and endothelial proliferation. The histological diagnosis was glioblastoma multiforme. The patient received gamma knife irradiation for the remnant lesion in the cerebellar vermis, and the lesions in the cerebellar hemisphere and left posterior limb of the internal capsule, and chemotherapy with temozolomide. However, multiple enhanced lesions were detected in the cerebellar vermis 2 months after the start of the temozolomide chemotherapy, and she died 8 months later. This case suggests that glioblastoma multiforme could develop in the long term after initial treatment for gliomatosis cerebri, and in a location separate from the initial lesion.

The aim of this study was to explore whether (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) is suitable to elucidate multidrug resistance and prediction of potentiation of antitumor agents by second-generation MDR1 inhibitors (PSC833, MS-209) in malignant brain tumors in rat. Malignant tumor cells (RG2 and C6 gliomas, Walker 256 carcinoma) were incubated with low dose vincristine (VCR) to induce multidrug resistance. MTT assay demonstrated a significant increase of surviving fractions in VCR-resistant sublines compared to those of drug-naive cells. Reverse transcriptase polymerase chain reaction revealed higher expression of MDR1 mRNA in VCR-resistant cells than drug-naive cells in each line. Volume distribution (V(d)) of (99m)Tc-MIBI was negatively correlated with MDR1 mRNA expression among drug-naive and VCR-resistant cells. MDR1 inhibitors decreased surviving fractions and increased V(d) of (99m)Tc-MIBI significantly in VCR-resistant sublines, whereas MDR1 mRNA expression was unchanged. These findings indicate that (99m)Tc-MIBI efflux was functionally suppressed by MDR1 inhibitors. Autoradiographic images of (99m)Tc-MIBI revealed higher uptake in drug-naive cells at basal ganglia compared with VCR-resistant cells at the opposite basal ganglia of rats. Oral administration of the second-generation MDR1 inhibitors significantly increased (99m)Tc-MIBI accumulation of both tumors. Therapeutic effects of VCR with or without the MDR1 inhibitors were also evaluated autoradiographically using (14)C-methyl-L-methionine ((14)C-Met) and MIB-5 index. (14)C-Met uptake and MIB-5 index of both tumors treated with VCR following the MDR1 inhibitor treatment significantly decreased compared with tumors treated with VCR alone. Analysis of (99m)Tc-MIBI accumulation is considered informative for detecting MDR1-mediated drug resistance and for monitoring the therapeutic effects of MDR1 inhibitors in malignant brain tumors., ((c) 2007 Wiley-Liss, Inc.)

Objective: (123)I-metaiodobenzylguanidine (MIBG) has been developed as a functional analog of the neurotransmitter norepinephrine. The success of MIBG as an imaging agent for neural crest tumors is derived from its chemical similarities to norepinephrine. The present study aimed to explore a potential of (123)I-MIBG to differentiate embryonal tumors from other types of brain tumors., Methods: Sixteen patients with brain tumors including three medulloblastomas, one neuroblastoma, six gliomas, and six meningiomas were examined with single-photon emission computerized tomography (SPECT) using (123)I-MIBG. The (123)I-MIBG uptake of tumors was defined as the ratios of tumor/nontumor (early and delayed T/NT) on SPECT images scanned 30 min and 6 h after intravenous injection of the tracer, respectively. Retention index was calculated as (delayed T/NT - early T/NT)/early T/NT., Results: The T/NT ratios on the early images for embryonal tumors (medulloblastomas and neuroblastoma), gliomas, and meningiomas were 3.2+/-1.7 (mean+/-SD), 1.4+/-0.3, and 1.6+/-0.5, respectively. The early uptake was significantly higher in the embryonal tumors than in gliomas (P<0.05). Delayed T/NT ratios for embryonal tumors were increased compared to the early T/NT ratios, while in contrast delayed T/NT ratios for the other tumors remained low (1.2-1.7). The high retention indices of the embryonal tumors indicate specific uptake of (123)I-MIBG in the tumors., Conclusion: Early high accumulation and high retention on delayed imaging may indicate a possibility of (123)I-MIBG SPECT in differentiating embryonal brain tumors from gliomas and meningiomas.

Three-dimensional imaging with MRI is a useful method for neurosurgical simulations. As in our previous study, we have constructed three-dimensional surface anatomical scanning (3D-SAS) from the data of contrast enhanced 3D fast spoiled gradient recalled acquisition in the steady state (3D-FSPGR) sequence. Using this technique, it is possible to generate 3D images from the data of only one acquisition, without using the fusion function. In our previous study, we did not compare the 3D images with the operative views at surgery. In the present study, two radiologists and one neurosurgeon assessed the 3D images in comparison with the operative views. There were problems in some cases, including unclear cortical sulci owing to brain swelling, lack of depiction of the cortical veins owing to meningeal enhancement, inadequate distinction between pial veins and meningeal veins, and so forth. However, in the majority of cases, 3D-SAS with 3D-FSPGR was able to demonstrate good anatomical conformity with the operative views, indicating the clinical usefulness of this technique.

We reported a rare case of cervical glioblastoma with intracranial dissemination at an early stage of clinical course and reviewed the literature. An 8-year-old girl presented with failure of vision 3 months prior to admission to our hospital. Neurological examination on admission disclosed no definitive abnormalities except for bilateral visual disturbance and optic atrophy. Cranial MR images revealed a homogeneously enhancing tumor in the left sylvian fissure. Multiple spotty T2-hyperintensity lesions without contrast enhancement were also disclosed in bilateral cerebellum. Spinal MR images showed an enhancing tumor at C7 and tiny enhancing lesions on the surface of T11. The patient underwent an uneventful excision of the exophytic tumor at C7. The histological diagnosis was glioblastoma. The enhancing tumor in the left sylvian fissure treated by Linac stereotactic radiotherapy with a marginal dose of 38.4Gy in 12 fractions has diminished, whereas the residual tumor at C7 remained unchanged after radiation of 44Gy. In contrast, the multiple spotty lesions without contrast enhancement dispersedly spread in the cerebellum and infiltrated into brain stem despite 4 courses of chemotherapy using ifosfamide, cisplatin, and etoposide. Stereotactic biopsy of the multiple spotty lesions in the cerebellum was performed. Histological examination revealed anaplastic astrocytoma. The patient died 2 weeks after the biopsy despite additional chemotherapy and focal irradiation to the cerebellum. Early detection and selection of optimal therapeutic strategies are important in management of spinal glioblastoma with subarachnoid dissemination, since neuroradiological findings and therapeutic sensitivity are varied according to differentiation of disseminated tumors.

Unlabelled: Assessments of herpes simplex virus 1 thymidine kinase (HSV-tk)/ganciclovir (GCV) treatment response, early in the course of therapy, are important in the evaluation and clinical management of patients. This study addresses whether imaging amino acid transport, glucose utilization, and passive vascular permeability provides an early indication of treatment response and can predict long-term outcome., Methods: Fischer 344 rats with intracerebral HSV-tk transduced RG2TK+ xenografts were studied. GCV-treated (50 mg/kg twice daily) and saline-treated control animals were compared; triple-label quantitative autoradiography was performed 3 d after initiating treatment, and long-term survival was determined. Autoradiograms of (18)F-FDG, (67)Ga-diethylenetriaminepentaacetic acid ((67)Ga-DTPA), and (14)C-aminocyclopentane carboxylic acid ((14)C-ACPC) were obtained; measurements of (14)C-ACPC and (67)Ga-DTPA plasma clearance (K(1)), (14)C-ACPC transport ( partial differential K(1)), relative glucose utililization (R), and normalized radioactivity (% dose/g) were obtained in tumor and brain tissues. Adjacent sections were stained to detect apoptotic cells, microvessels, and type L neutral amino acid transporter in tumor and normal brain., Results: GCV treatment reduced partial differential K(1) and % dose/g of (14)C-ACPC in RG2TK+ xenografts to approximately 30% of that in nontreated animals (from 34 +/- 9 [mean +/- SD] to 9.5 +/- 2.7 microL/min/g and from 0.28 +/- 0.09 to 0.11 +/- 0.04 % dose/g, respectively). GCV had a significant but substantially smaller effect than toxicity on glucose utilization and little or no effect on passive vascular permeability of RG2TK+ xenografts. These differences could not be explained by differences in plasma amino acid or glucose concentration at the time of the study. Histology revealed a large fraction of dead tumor cells and only a sparse distribution of apoptotic cells in GCV-treated tumors. Many CD34-positive endothelial cells in GCV-treated tumors showed only weak or marginal LAT1 staining, whereas CD98 staining remained unchanged. Survival was significantly increased by GCV treatment from 18 +/- 4 to 56 +/- 17 d., Conclusion: (14)C-ACPC influx, K(1)(ACPC), facilitated transport, partial differential K(1)(ACPC), and % dose/g (ACPC) are good indicators of early treatment response after HSV-tk/GCV gene therapy. The parametric images and changes in K(1)(ACPC), partial differential K(1)(ACPC), and % dose/g (ACPC) are substantial and are better than the corresponding measures obtained in the same animals and in the same tissue (tumor) regions with (67)Ga-DTPA and (18)F-FDG. Amino acid transport imaging may be a good surrogate paradigm to monitor treatment response of brain tumors.

Between 1985 and 2001, eight patients with intracranial ependymomas underwent surgery at our hospital. The cases included six infratentorial ependymomas, one supratentorial ependymoma and one supratentorial anaplastic ependymoma. Infratentorial ependymomas were classified according to origin and extension. The lateral type tumors originated from the lateral part of the fourth ventricle in four cases. The midfloor type tumors originated from the inferior half of the fourth ventricular floor in two cases. The three totally resected tumors were the lateral type tumors. The remaining one case with the lateral type tumor underwent nearly total resection of the tumor, since the tumor involved lower cranial nerves. All patients with the midfloor type tumors underwent incomplete resections of the tumors, because the tumors infiltrated into brain stem. Lower cranial nerve involvement and brain stem invasion implied incomplete resection and had the poor prognosis. In intracranial ependymomas, all four patients with total resections have been alive, whereas three of four patients with incomplete resections have died. The mean survival time of all patients with intracranial ependymomas was 127 months from the time of the initial surgery. There were no deaths in the patients with tumors showing MIB-1 index < 10% (n = 4). The mean survival time of the patients with tumors showing MIB-1 index > or = 10% (n = 4), was 30 months. The extent of the resection, the age of the patients and MIB-1 index are important factors in the outcome in patients with intracranial ependymomas. Two representative children aged less than 3 years with the midfloor type tumors were presented. In a patient treated with conventional radiation and chemotherapy, residual tumor repeatedly enlarged within 12 months despite several resections of the tumor. The patient died 32 months after the initial resection. In contrast, the other patient received multidisciplinary treatment including Linac stereotactic radiotherapy (SRT) with a marginal dose of 27 Gy in 9 fractions, have been still alive for 45 months after the initial resection. The residual tumor slightly decreased in size and remained stable without evident growth 12 months after SRT. SRT may provide good local control for patients with intracranial ependymomas and have a favorable impact on survival.

A case of astrocytoma with extracranial extension after malignant transformation is presented. The patient was a 58-year-old female who suffered from headache. The initial magnetic resonance imaging (MRI) demonstrated a slightly hyperintense tumor on T 2-weighted images in the tip of the left temporal lobe, and no contrast enhancement on gadolinium-enhanced T 1-weighted images(Gd-T 1 WI). On digital subtraction angiography, there was no tumor staining. The initial diagnosis was made as low-grade astrocytoma. However two months later, her symptoms aggravated suddenly. MRI revealed a remarkably growing tumor with ring-like enhancement on Gd-T 1 WI. She underwent a temporal lobectomy, which pathologically demonstrated a glioblastoma. After surgery, chemotherapy and radiotherapy were performed. The tumor invades the skull base and extended into the infratemporal fossa 25 months after surgery.

We report a rare case of a primary intracerebral malignant fibrous histiocytoma (MFH) with malignant progression from a premalignant stage. A 73-year-old male presented with mild hemiparesis on the right side of his body 4 months prior to admission. MR images showed a homogenously enhanced mass in the left parietal lobe. The patient underwent an uneventful extirpation of the solid mass. Microscopically, the solid tumor contained histiocytic cells and spindle-shaped fibroblastic cells arranged in a storiform pattern. The tumor cells were immunoreactive for vimentin, MAC 387 (macrophage marker) and alpha-1-antitrypsin. The MIB-1-positive rate was 1%. The histological diagnosis was fibrous histiocytoma. Postoperative MR images demonstrated no abnormally enhanced lesions. The patient's neurological symptoms and signs gradually improved. One year after surgery, he developed right hemiparesis. MR images showed a heterogeneously enhanced mass in the left sensorimotor area. This recurrent tumor was totally resected. Microscopically, the tumor was composed of atypical spindle-shaped cells, forming a storiform pattern. Pleomorphism was prominent, and necrotic foci were also seen. The MIB-1 labeling index averaged 11%. The histological findings corresponded to those of MFH. Unfortunately, the patient died of interstitial pneumonia contracted during postoperative radiotherapy. Early detection and resection at a stage of low malignant potential, followed by radiochemotherapy, are crucial for the management of this mesenchymal tumor.

A case of frontal atypical teratoid/rhabdoid tumor (AT/RT) was presented in the findings of single-photon emission computerized tomography (SPECT) using 201Tl-chloride (Tl) and 123I-metaiodobenzylguanidine (MIBG), and positron emission tomography using 18F-fluorodeoxyglucose (FDG) and (11C-methyl)-L-methionine (Met). A 16-year-old female had an episode of Jacksonian seizures one month prior to admission. CT scans showed an isodensity mass with heterogeneous enhancement in the left frontal lobe. MR images revealed a tumor with solid and cystic components and perifocal edema. SPECT demonstrated intense accumulation of Tl and MIBG in the enhancing lesion 15 min and 30 min after intravenous injection of tracers, respectively. The 6-hr delayed SPECT showed no retention of MIBG in the enhancing lesion. FDG-PET and Met-PET revealed high uptake of tracers in the enhancing lesion. Met did not accumulate in the frontal white matter, which appeared hyperintense on T2-weighted MR images. The patient underwent an uneventful extirpation of the solid mass, where Met had accumulated. Microscopically, the solid tumor contained rhabdoid cells, spindle-shaped cells resembling mesenchymal cells, and nests of small cells. The tumor cells were immunoreactive for vimentin, cytokeratin, and epithelial membrane antigen. The MIB-1 labeling index was 25%. The histological diagnosis was AT/RT. Postoperative course was uneventful. A dose of 32.4 Gy was administrated to the whole brain and a boost of 27.8 Gy to the T2-hyperintensity lesion. Five months after the radiotherapy, MRI showed neither abnormal enhancing lesions nor the T2-hyperintensity lesion. Multifarious studies using SPECT and PET are useful for differential diagnosis and for choosing optimal therapeutic strategy for this type of tumor.

A patient with Moyamoya-like vessels after radiation therapy for treatment of a tumor in the basal ganglia is reported. He was diagnosed as Down syndrome at birth. He had a tumor in the left basal ganglionic region at 12 years of the age. The tumor increased in size at age 14. He underwent cerebral angiography, which did not show a stenosis nor occlusion of the internal carotid artery, anterior cerebral artery, nor the middle cerebral artery. He received radiation therapy with a total dose of 56 Gy. He presented a dressing apraxia at age 19. MRI showed cerebral infarction in the left temporo-occipital region. Right internal carotid angiography revealed a severe stenosis of the internal carotid artery and anterior cerebral artery as well as a severe stenosis of the middle cerebral artery on the right side. Moyamoya-like vessels were seen in the basal ganglionic region. Left internal carotid angiography also showed a stenosis of the internal carotid artery and anterior cerebral artery as well as a severe stenosis of the middle cerebral artery on the left side. Moyamoya-like vessels were seen in the basal ganglionic region. Leptomeningeal anastomose and transdural anastomose were bilaterally seen. These arterial occlusion and stenotic phenomenon corresponded to a previous radiation field. These Moyamoya-like vessels with arterial stenosis and occlusion were thought to be due to radiation-induced vasculopathy, because a previous cerebral angiography showed a normal caliber of cerebral arteries. This patient showed that patients with radiation therapy in their early childhood should be carefully observed considering the possibility of this phenomenon.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, has been investigated as a potent mediator of brain tumor angiogenesis and tumor growth. We evaluated the effect of VEGF expression on the pathophysiology of tumor growth in the brain. Human SK-MEL-2 melanoma cells, with minimal VEGF expression, were stably transfected with either sense or antisense mouse VEGF cDNA and used to produce intracerebral xenografts. Vascular permeability, blood volume, blood flow, and tumor fluorodeoxyglucose metabolism were assessed using tissue sampling and quantitative autoradiography. Tumor proliferation was assessed by measuring bromodeoxyuridine labeling indices. Tumor vascular density and morphological status of the blood-brain barrier were evaluated by immunohistochemistry. SK-MEL-2 cells transfected with sense VEGF (V+) expressed large amounts of mouse and human VEGF protein; V+ cells formed well-vascularized, rapidly growing tumors with minimal tumor necrosis. V+ tumors had substantial and significant increases in blood volume, blood flow, vascular permeability, and fluorodeoxyglucose metabolism compared to wild-type and/or V- (antisense VEGF) tumors. VEGF antisense transfected V- expressed no detectable VEGF protein and formed minimally vascularized tumors. V- tumors had a very low initial growth rate with central necrosis; blood volume, blood flow, vascular permeability, and glucose metabolism levels were low compared to wild-type and V+ tumors. A substantial inhibition of intracerebral tumor growth, as well as a decrease in tumor vascularity, blood flow, and vascular permeability may be achieved by down-regulation of endogenous VEGF expression in tumor tissue. VEGF-targeted antiangiogenic gene therapy could be an effective component of a combined strategy to treat VEGF-producing brain tumors.

The aim of the present study is to understand the therapeutic effects of recombinant human tumor necrosis factor-alpha (rH-TNF) on hemocirculation and metabolism of brain tumors. Using double-label autoradiographic technique, we have monitored changes in regional cerebral blood flow (rCBF) and protein-bound fraction of (3H-methyl)-L-methionine, expressed as acid-insoluble fraction (AIF), in rat brain tumors following treatment with intracarotid rH-TNF. The central portion of tumors showed a significant decrease in rCBF and AIF at 4 hours after the injection (p < 0.01, p < 0.05, respectively, as compared with non-treated control rats), turned microscopically necrotic at 24 hours, and became more extensively necrotic at 72 hours. Tumor cells remained viable only in the peripheral portion of the tumors after the treatment. The peripheral portion also showed a moderate decrease in rCBF, but less change in AIF to 4 to 72 hours after the treatment. Neither ipsilateral nor contralateral non-involved cortex demonstrated appreciable changes in rCBF and AIF during the observed period. Intracarotid rH-TNF selectively reduces tumor rCBF and AIF, resulting in histological modification.

To accurately differentiate nontumor central nervous system (CNS) diseases from brain tumors, we retrospectively evaluated the cerebral circulation and metabolism in patients with nontumor CNS diseases using positron emission tomography (PET). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), the metabolic rates of oxygen (rCMRO2), and of glucose (rCMRGI), and the uptake of 11C-methyl-L-methionine (11C-Met) were visually evaluated in lesions and compared with values for the contralateral white matter regions. PET findings were correlated with those of x-ray computed tomography (CT) and magnetic resonance imaging (MRI), and were analyzed for nontumor CNS diseases and cerebral gliomas. rCBF and rCBV were changeable from disease to disease or from stage to stage of disease progression. rOEF and rCMRO2 remained low in 5 and 6, respectively, of 9 nontumor CNS diseases examined, whereas these parameters were increased in CNS infections such as brain abscess. Overall, noteworthy was the locally increased rOEF and rCMRO2 in the patients with a brain abscess in contrast to the values for patients with gliomas. rCMRGI reflected biological characteristics of each disease, and correlated with cell density, whether reactive glial cells or inflammatory cells. 11C-Met was accumulated at a certain stage of nontumor CNS diseases, which implied uptake of the tracer as a result of disruption of the blood-brain barrier as well as metabolic incorporation.

A 56-yr-old housewife with cerebral astrocytoma was reported with positron emission tomography findigns using 11C-methyl-L-methionine (11C-Met) and 18F-fluorophenylalanine (18F-Phe) tracers. 11C-Met and 18F-Phe accumulated intensely in tumor lesions, although CT scans showed only a foggy low-density area. Five years and one month after, an enhancing mass appeared on CT scans. Thus, amino acid tracers may play a important role in the early diagnosis of gliomas.

cis-diamminedichloroplatinum (II) (CDDP) has been used both alone and in combination with other chemotherapeutics for cancer chemotherapy. Although CDDP acts primarily on DNA, it can also act at the tumor-cell membrane to inhibit methionine transport. The latter mechanism of CDDP is reported to have an important role as a chemical modulator in enhancing chemotherapeutic effects of 5-fluorouracil in tumor cells. We report here the effects of CDDP on methionine uptake in an in vivo brain-tumor model. C6 brain-tumor cells were stereotactically inoculated in the right basal ganglia of 6-week-old male Sprague-Dawley rats. Ten days after the inoculation, autoradiographic images were obtained using (14C-methyl)-L-methionine. The tracer uptake, represented as differential absorption ratio (DAR) and an acid-insoluble fraction (AIF), was measured in both brain tumors and normal brain with or without an intravenous injection of CDDP. The tumor/non-tumor DAR and AIF decreased significantly (P < 0.01, as determined by the Mann-Whitney U-test) after CDDP treatment, whereas the non-tumor DAR and AIF remained almost unchanged. These findings indicate that CDDP inhibits methionine uptake selectively in brain-tumor tissue and may therefore be a potent chemical modulator in the chemotherapy of brain tumors.

To elucidate the mechanism of large neutral amino acid (LNAA) transport in cerebral gliomas and to evaluate the clinical usefulness of positron emission tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18 patients with cerebral glioma using dynamic PET and 18F-Phe. By employing two-compartment model analysis, the influx rate K1, the efflux rate k2 and the distribution volume (Vd) of 18F-Phe were estimated in tumour tissue and contralateral normal grey matter. 18F-Phe showed increased accumulation in tumour tissue regardless of the grade of malignancy in all patients. The rate of uptake of 18F-Phe in high-grade glioma was significantly higher than in low-grade glioma (P <0.05). However, it was difficult to evaluate the tumour grade only from the 18F-Phe accumulation in individual cases. Values of K1 and Vd were significantly increased in the tumour tissue. The K1 value of the tumour tissue tended to decrease with increasing LNAA concentration in plasma. Therefore, influx of 18F-Phe into tumour tissue is mainly related to the carrier-mediated active transport. It is concluded that PET with 18F-Phe is of clinical value for tumour detection rather than assessment of tumour malignancy.

The aim of this study was to evaluate efficacy of high dose chemotherapy and restoration of hamatopoiesis following peripheral blood stem cell transplantation (PBSCT). Three patients with pediatric malignant brain tumors (two medulloblastomas and one medullomyoblastoma) underwent high dose chemotherapy including CBDCA, VP-16, and MCNU with PBSCT. Postcontrast-MR images revealed no abnormal enhancing lesions after high dose chemotherapy in all patients. One patient with medulloblastoma has remained complete remission one year and seven months after the termination of treatment. Another patient with medullomyoblastoma died of respiratory distress syndrome one month after the second course of high dose chemotherapy. The other patient with medulloblastoma, which received PBSCT and high dose chemotherapy at the time of tumor recurrence after failure of initial treatment, suffered from multiple disseminated lesions five months after the treatment. PBSCT contributed prompt recovery from hematopoietic dysfunction in all patients. These results indicate that PBSCT may play an important adjuvant to chemotherapy and further offer a safer and more effective high dose chemotherapy in pediatric malignant brain tumor patients.

Non-invasive positron emission tomography (PET) was performed to identify changes in blood flow and metabolism, specific to early stages of tumour occurrence or recurrence. 2 patients with slowly progressive gliomas from early to late stages of tumour development were analysed by serial PET measurements of circulation and metabolism using 15O-gas and 18F-fluorodeoxyglucose. PET revealed a persistent depression of oxygen metabolism, as indicated by the regional oxygen extraction fraction or metabolic rate of oxygen, in the regions where tumours were later found. Abnormal blood flow and metabolism may precede the morphological changes detected by computed tomography (CT) in patients with gliomas.

11C-methyl-L-methionine (C-11 Met)PET, CT and MR imaging were performed in eleven patients with malignant brain tumors before and after RT to evaluate the usefulness of positron emission tomography (PET) in monitoring tumor response to radiotherapy (RT). The subjects included five cases of intracranial malignant lymphoma (ICML) and six cases of glioma. C-11 Met uptake by the tumor (T) and the contralateral gray matter (NT) was calculated on the PET images. The mean T/NT ratio of the ICMLs and gliomas changed from 2.33 and 1.87, respectively, before RT to 1.31 and 1.58, respectively, after RT.No significant difference was found between the T/NT ratios before and after RT in either the ICMLs or the gliomas (t-test). We tentatively defined the minimum T/NT ratio, 1.2, as the threshold between tumor and nontumor regions. Tumors with a ratio of 1.2 or more were imaged as "hot" (MET) and coincided with CT or MR image lesions which were visualized as contrast-enhancing (CE) and low-density (LD) or high-intensity (HI). The relationships between PET, CT and MRI lesions were classified as follows: Type I (MET < or = CE), Type II [CE < MET < LD (HI)], Type III [LD(HI) < or = MET]. MET lesions extending regionally ( > 1 cm) beyond the respective CT or MR image lesions were designated "MET-extension" and LD (HI) lesions protruding ( > 1 cm) beyond the MET lesions were recorded as "LD (HI)-extension" on the integrated images. The type II pattern of the MET areas in all five cases of ICML before RT had changed to Type I in one case, Type III in one case and Type II in three cases, after RT, while the two Type II patterns and four Type III patterns of the gliomas had converted to four Type II and two Type III patterns. These findings indicate that gliomas tend to invade into areas of peritumoral edema more than ICMLs. There were two ICML MET-extension sites in the cortex before RT, as opposed to two in the cortex, one in the basal ganglia, one in the thalamus, and one in the corpus callosum among the gliomas. On follow-up CT or MR images MET-extension (75%) had converted to a CE or LD (HI) region. Four ICML LD (HI)-extension sites before RT were found in periventricular white matter, versus one in the cortex and three in the white matter among the gliomas. LD (HI)-extension appeared to represent vascular edema because it decreased or diminished after completion of therapy. Sequential analysis of integrated C-11 Met PET, CT and MR images is useful in detecting the extent of tumor infiltration by ICMLs and gliomas, particularly at an early stage, and for evaluating the effect of RT in the treatment of both.

We measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with meningioma. Ten patients including one recurrent case, two males and eight females aged from 44 to 71 years with a mean age of 54 years old, were studied prior to surgical interventions. Histological diagnosis was as follows: seven cases of meningothelial type, two cases of angiomatous type and one fibrous type. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter in comparison with eight cases with malignant gliomas (five cases of malignant astrocytoma and three cases of glioblastoma, aged from 14 to 70 years with a mean age of 41 years old). Hemocirculation of the tumor was exceedingly higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Low rOEF implicated an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl) suggested rather aerobic glycolysis as compared with malignant gliomas. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment model of 18F-fluorodeoxyglucose (FDG). Tumor k1 and k2 values markedly increased in all examined cases, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral hemocirculation and glucose metabolism in a malignant astrocytoma were repeatedly quantified before and after intracarotid injection of recombinant human tumor necrosis factor-alpha (rH-TNF) using positron emission tomography (PET). The patient received an intracarotid injection of a 3 x 10(4) U/m2 dose of rH-TNF three times over a two week period. PET was performed prior to and 24 hr after the first injection, and two weeks after the third injection. Prior to the first rH-TNF treatment, two lesions demonstrating high perfusion and hypermetabolism of glucose were noted in the right frontal and temporal regions. The frontal hypermetabolic lesion showed decreases in hemocirculation and metabolism 24 hr after the first injection and then increases beyond the pre-treatment level two weeks after the third treatment, whereas the temporal lesion remained unchanged during the follow-up period. No appreciable changes were noted in the adjacent cortex where rH-TNF was perfused, with the exception of a transient decrease in regional blood volume. Magnetic resonance images of the tumor showed no changes as a result of treatment with intracarotid rH-TNF. Intracarotid rH-TNF preferentially affects tumor tissue as opposed to normal cortex.

Background: Noninvasive measurements of cerebral circulation and metabolism may be useful for diagnosis in patients with brain tumors. The authors tested the prognostic significance of circulatory and metabolic values or ratios determined by positron emission tomography (PET) in patients with gliomas., Methods: The subjects were 23 patients, who underwent a complete PET study of cerebral circulation and metabolism with long-term follow-up of at least 57 months. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction, and the metabolic rates of oxygen (rCMRO2) and glucose (rCMRGl) were measured before treatment. Data regarding tumors, the contralateral gray matter and white matter, and the ratio between tumor and gray matter or between tumor and white matter were compared with survival time from the time of the PET study. Prognostic factors were tested using Cox's regression analysis., Results: Among clinical parameters, histologic grade and performance status were important variables regulating survival. When survival times of patients with values or ratios equal to or higher than the median were compared to those of patients with values or ratios lower than the median, significant determinant PET measurements were tumor rCMRGl and the ratios of tumor:gray rCMRGl and tumor:white rCMRGl. Median survival time in the patients with an rCMRGl value of 4.4 mg/100ml/minute (median value) or more indicated 9 months, which was significantly shorter than greater than 113 months in the patients with a value lower than the median (P = 0.003 by the generalized Wilcoxon test). Patients with a higher value of gray rCBF, rCBV, or rCMRO2 had significantly longer survival times than those with a lower value., Conclusions: Cerebral circulation and metabolism as determined by PET can be of ancillary significance in predicting the prognosis of patients with gliomas.

A case of radiation-induced vasculopathy of a pineal glioma was presented with haemodynamic and metabolic changes before and after radiotherapy. After radiation of 60 Gy with conventional fractionation (1.8-2.0 Gy daily, 5 days per week), regional blood flow, oxygen extraction fraction, metabolic rate of oxygen, kinetic metabolic rate of glucose and the rate constants (K2, K3) were markedly depressed (20% or greater) compared with the pre-irradiated study. 7 months after radiotherapy, the patient developed transient transient episodes of both right and left upper limb convulsion, terminating in generalized convulsion. When she developed status epilepticus, computed tomography showed extensive low density areas in the territory supplied by the right middle cerebral and the right posterior cerebral arteries. Cerebral angiography revealed diffuse stenosis at both carotid bifurcations and at the origins of the right posterior communicating and posterior cerebral arteries. Haemodynamic and metabolic depression therefore implicated radiation-induced vasculopathy in the present case.

Primary central nervous system (CNS) involvement of non-Hodgkin's lymphoma is uncommon and a vast majority of reported cases are of B-cell origin. We present a 52-year-old woman with primary peripheral T-cell lymphoma of the brain. Immunostaining of paraffin-embedded sections proved tumor cells to be positive for T-cell markers MT1 and UCHL1, and negative for B-cell markers MB1, and 4KB5. Radiotherapy combined with steroid therapy rendered neurologic recovery and complete tumor remission confirmed by computed tomography and magnetic resonance imaging. From a review of documented 19 cases of primary CNS T-cell lymphoma including the present case, this disease is characterized by poor prognosis among CNS lymphomas.

Autoradiographic study of (14C-methyl)-L-methionine with brain tumor bearing rats aimed at an elucidation of the mechanism of tracer accumulation in the protein synthesis of tumor. Twice as much tracer accumulated in the tumors compared as in the contralateral gray matter (nontumor region) at 90 min post intravenous injection. The protein-bound fraction of the tumors, expressed as acid-insoluble fraction (AIF), was 1.7 +/- 0.6 (mean +/- standard deviation, n = 6), significantly higher than that (0.8 +/- 0.2) of the nontumor region (p < 0.05 by the Mann-Whitney test). The tumor AIF comprised 82.3 +/- 9.2% of the total amount of the tracers accumulated in the tumors. The protein synthesis inhibitor cycloheximide reduced the tracer uptake and the AIF of the tumors to an almost same level as the nontumor region. These findings indicate that metabolic acceleration of protein synthesis may be a main reason for the high accumulation of (14C-methyl)-L-methionine in tumor.

To elucidate metabolic pathways of methionine in brain tumors, we studied autoradiographic images of (14C-methyl)-L-methionine (14C-Met) in transplanted rat brain tumors. 14C-Met accumulated in the tumor almost twice as much as in the gray matter 90 min after injection. The acid-insoluble fraction, which was bound to macromolecules, comprised 84% the total count of the accumulated tracers in the tumor. Analysis of 14C-Met tracer accumulation is informative for understanding amino acid metabolism in brain tumors.

Two cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) using 11C-methyl-L-methionine (11C Met). Lesions delineated by 11C Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake of 11C Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma.

A case of gliomatosis cerebri was studied with positron emission tomography (PET). Carbon-11-L-methionine (11C-Met) accumulated in the diffusely infiltrative tumorous area more widely and accurately than the lesion detected by conventional x-ray computerized tomography (CT) or magnetic resonance (MR) imaging. Autopsy findings three months after the time of the PET study showed good anatomical correspondence between the extent of densely aggregated tumor cells and the region with high uptake of 11C-Met. PET may offer an innovative approach in the delineation of gliomatosis cerebri, which has not been clearly recognized by CT or MR.

Sixteen patients with gliomas (7 low grade, 9 high grade) were examined using positron emission tomography (PET) with intravenous administration of 22.2 MBq/kg (0.6 mCi/kg) of (11C-methyl)-L-methionine (C-11 Met). The tracer uptake in regions of interest was calculated on PET images taken 45 minutes after injection; the uptake index was represented as a percentage of the total count in the arterial blood summed over 45 minutes. C-11 Met uptake indices in the tumors ranged from 0.020 to 0.041% with a mean of 0.032% for the low-grade gliomas and from 0.013 to 0.044% with a mean of 0.036% for the high-grade gliomas. These indices significantly increased as compared with those in the contralateral gray matter (0.008-0.032% with a mean of 0.023%; p less than 0.01 vs. low-grade gliomas, p less than 0.001 vs. high-grade gliomas). In the low-grade gliomas, C-11 Met PET images clearly depicted the existence and even the extent of the tumors, although x-ray computed tomography (CT) did not always distinguish tumoral lesions. In the high-grade gliomas, the areas of tracer accumulation regionally extended to peritumoral low density on CT scans, where malignant tumor cell infiltration was proved by operative and follow-up CT findings. C-11 Met may be a useful radiopharmaceutical for differential diagnosis of gliomas, and the accuracy of tumor localization will give us a better rationale in therapeutic strategies for surgery and radiation therapy of gliomas.

Presented is a retrospective study of 20 patients with intracranial germ cell tumors who the authors have treated during past 10 years. The cases among these patients included thirteen germinomas, three teratomas, two embryonal carcinomas, and two malignant teratomas. A ventriculoperitoneal shunt was installed in 15 cass and the tumor was surgically removed in four cases. All cases were irradiated with 33 to 61 Gy; in 18 cases, more than half of the total dose was delivered to the whole brain, and in 9 cases, spinal irradiation was given because of a verified CSF dissemination. Chemotherapy was the regimen for four cases. The tumor responded to therapy in 16 (84%) of 19 evaluable cases. Overall, the median and five year survival were 102 months and 83%, respectively. The survival rate was found to vary between the benign group (germinoma, teratoma) and the malignant group (embryonal carcinoma, malignant teratoma, germinoma with STGC) (p less than 0.01).

The aim of this study was to evaluate effects of radiochemotherapy on blood flow and metabolism using C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose positron emission tomography (PET). Conventional, external radiotherapy (180-200 cGy/5 fractions/week) using 60Co or a 10 MV linear accelerator was given in conjunction with chemotherapy of nimustine hydrochloride (ACNU) and tegafur (FT-207) in eight patients with gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2), and glucose consumption (rCMRG1) were longitudinally examined before the treatment, and at an early stage (within one month) and a late stage (three to thirty-one months with a mean of 12 months) after radiochemotherapy. Contralateral gray and white matter to the tumor was selected as regions of interest (ROIs), because these portions were irradiated with larger doses compared to other brain parenchymal regions through parallel opposing fields. Maximum doses to the ROIs varied between 20 and 61 Gy. Calculated as a function of time-dose-fractionation, nominal standard doses (NSD) ranged from 566 to 1729 ret, and 344 to 1062 neuret; equivalent doses (ED) equaled 432 to 1327 rads. At the early stage, rCBF and rCBV increased in the contralateral gray and white matter; gray matter rOEF decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, probably due to decompression of the tumor bulk and radiochemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

We tested clinical significance of hemocirculatory and metabolic values and ratios as determined by positron emission tomography (PET) in twenty-three patients with cerebral gliomas. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rates of oxygen (rCMRO2) and glucose (rCMRGl) were measured prior to treatment using PET with 15O2, C15O, 15O2, and 18F-fluorodeoxyglucose tracers. For the quantitative analysis, regions of interest were delineated on tumor regions including peak activity, the contralateral gray and white matter. The regional values and the ratios of tumor/gray matter and tumor/white matter were compared to performance status (PS) according to the five functional grades system which are defined by the Japan Society for Cancer Therapy, tumor progression-free time (PFT), survival time (ST) from the time of the PET study, regardless of type of therapy. As with rCMRGl, the tumor values and the ratios of tumor/gray matter and tumor/white matter correlated significantly with PS (tumor/gray: p less than 0.05, tumor/white: p less than 0.01). Both the gray rCBF and the tumor/gray rCBF ratio had close relation with PS and/or PFT (p less than 0.05). The gray matter rCMRO2 and the tumor/gray matter rCMRO2 ratio related significantly (gray matter: p less than 0.01, tumor/gray: p less than 0.05) to each clinical parameter of PS, PFT, and ST. These indicate that values and ratios as determined by PET can be useful in predicting the prognosis of glioma patients.

A high resolution positron emission tomography (PET), HEADTOME III, has enabled us to visualize heterogeneous parts, i.e. viable, necrotic, and edematous portions in malignant gliomas, and to quantify regional hemocirculation and metabolism of the tumors using 15O and 18F-fluorodeoxyglucose tracers. Hemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2) and glucose consumption (rCMRGl) were studied in eight patients with untreated malignant gliomas. Regions of interest (ROIs) in PET images were focused on lesions corresponding to contrast enhancing areas, central low density areas of the tumors, and peritumoral low density areas in CT scans. In the viable portion of the gliomas, rCBV (5.20 +/- 1.18ml/100ml, mean +/- SD, n = 8) was significantly higher than that of the contralateral gray matter (p less than 0.05), which is suggestive of high vascularity; rOEF (0.36 +/- 0.16) and rCMRO2 (1.66 +/- 0.45ml/100ml/min) values markedly decreased (p less than 0.05, p less than 0.01). On the other hand, rCBF (36.3 +/- 13.0ml/100ml/min) and rCMRGl (5.94 +/- 1.15mg/100ml/min) were similar to that of the contralateral gray matter. A relative dissociation between oxygen and glucose metabolism indicates anaerobic glycolysis in the energy metabolism of malignant gliomas. In the central low density area, rCBF, rCBV, rOEF, rCMRO2, rCMRGl values decreased significantly from the viable portion and the contralateral gray matter. rOEF was markedly reduced in the central low density area as compared with that of the peritumoral low density area. The rOEF reduction indicates that oxygen metabolism of gliomas is the first to fail, accompanied by autoregulatory impairment of vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

We have studied changes in the (11C-methyl)-L-methionine (C-11 Met) uptake index in six glioma cases subsequent to radiotherapy, using positron emission tomography (PET) to evaluate the effects of radiotherapy on the amino acid metabolism of the tumor. The uptake index of the tumor represented as a percentage of the total count in the atrial blood recorded during a period of 45 min, showed an average of 0.037% and 0.039% prior to and within two months after the therapy, respectively. Out of three cases where a fall in the index was seen, two cases showed tumor regression in the size of the contrast enhanced lesion measured by CT; all three cases had a relatively long period of clinical and neurological amelioration. However, following a short period of clinical improvement, the other three patients with a rise in the index showed no change or tumor progression on CT. These findings indicate that changes in the C-11 Met uptake index can be a sensitive and precise indicator for evaluating the effect of radiotherapy on gliomas.