Initial Positron Emission Tomography Scan Research Articles

P.030 Clinical findings, immunotherapy and neuroimaging results in Pediatric Anti-NMDA Receptor Encephalitis

Background: Anti-NMDAR Encephalitis is an autoimmune disease of children and adults which most often presents with sub-acute psychiatric disturbance or seizures, but includes a broad group of potential clinical manifestations. Routine neuroimaging, such as cerebral MRI, is often nonspecific or normal. Methods: This study reports a series of retrospectively reviewed pediatric patients with AntiNMDAR encephalitis with emphasis on the evolution of clinical features over time, cerebral MRI, 18-FDG Positron emission tomography (PET) findings, and post illness neurocognitive features. Results: Four cases of Antibody confirmed AntiNMDAR encephalitis were included, two male and two female, of a mean of 13 years of age. Patients had a mean of three symptom categories by presentation, though many of these were subtle, progressing to 6.5 by the end of the first month. MRI, CSF and EEG were abnormal for one, three and all patients, respectively. All patients had abnormal cerebral PET scans, and all displayed some temporal lobe hypermetabolism on either initial or repeat cerebral PET Scan. Conclusions: Anti-NMDAR encephalitis is a variable disorder with an evolving clinical presentation in children. Temporal hypermetabolism on cerebral PET may be a time dependent feature of the disorder.

Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug-resistant epilepsy.

We analyzed long-term changes of lobar glucose metabolic abnormalities in relation to clinical seizure variables and development in a large group of children with medically refractory epilepsy. Forty-one children (25 males) with drug-resistant epilepsy had a baseline positron emission tomography (PET) scan at a median age of 4.7years; the scans were repeated after a median of 4.3years. Children with progressive neurological disorders or space-occupying lesion-related epilepsy and those who had undergone epilepsy surgery were excluded. The number of affected lobes on 2-deoxy-2(18 F)-fluoro-D-glucose-PET at baseline and follow-up was correlated with epilepsy variables and developmental outcome. On the initial PET scan, 24 children had unilateral and 13 had bilateral glucose hypometabolism, whereas 4 children had normal scans. On the follow-up scan, 63% of the children showed an interval expansion of the hypometabolic region, and this progression was associated with persistent seizures. In contrast, 27% showed less extensive glucose hypometabolism at follow-up; most of these subjects manifested a major interval decrease in seizure frequency. Delayed development was observed in 21 children (51%) at baseline and 28 (68%) at follow-up. The extent of glucose hypometabolism at baseline correlated with developmental levels at the time of both baseline (r=.31, P=.05) and follow-up scans (r=.27, P=.09). In this PET study of unoperated children with focal epilepsy, the lobar pattern of glucose hypometabolism changed over time in 90% of the cases. The results support the notion of an expansion of metabolic dysfunction in children with persistent frequent seizures and its association with developmental delay, and support that optimized medical treatment to control seizures may contribute to better neurocognitive outcome if no surgery can be offered.

Impact of Staging With Positron-emission Tomography (PET) and Comorbidities on Management and Survival of American Veterans With Stage I-III Non–Small Cell Lung Cancer

The extent of whether staging by fluorodeoxyglucose positron-emission tomography (PET) impacts outcomes in American Veterans with stage I-III non-small-cell lung cancer (NSCLC) is unknown. We investigated impact of fluorodeoxyglucose PET staging and age-adjusted comorbidities (AACs) on management and survival of NSCLC in this group. We performed a retrospective review to identify with NSCLC who underwent initial PET scan and received care at the Ann Arbor Veterans Hospital between 2005 and 2010. Survival outcomes were estimated by Kaplan-Meier methods, quantile regressions, and Cox proportional hazards models, after accounting for age at diagnosis, sex, AAC, and initial treatment. The number of PET scans increased from 0 in 2005 to 66 in 2010. There were 170 men, 4 women, median age 64 years. Median AAC score was 4. In CS I (n=54), initial PET upstaged 5 patients. Median survival for no change in PET stage was 27.43 versus 67 months for upstaged patients (P=0.034). For CS II (n=15), initial PET scan upstaged 1 patient. Median survival for no change in PET stage was 16.53 versus 2.8 months for upstaged patient (P=0.335). For CS III (n=104), PET scan upstaged 20 patients. Median survival for no change in PET stage was 13.3 versus 3.8 months for upstaged patients (P=0.016). PET scans resulted in upstaging in 15% in CS I-III NSCLC. AAC scores dictated therapy decisions and outcomes more than PET staging. Veterans had lower 5-year survival rates (26.3%, 15.8%/13.4%) compared with 53% and 27% in age/sex/time-period matched SEER data for stage I-II/III NSCLC.

Stereotactic Body Radiation Therapy for Unbiopsied Early-stage Lung Cancer

Medically inoperable lung cancer patients often have comorbidities that preclude pathologic diagnosis from being attained. We perform a multi-institutional analysis to determine if unbiopsied early-stage lung carcinoma can be safely and effectively treated with stereotactic body radiation therapy (SBRT). Thirty-four patients with unbiopsied lung cancer were treated with SBRT at the University of Louisville or University of Virginia. Patients had computed tomography (CT) and positron emission tomography (PET) imaging clinically consistent with lung malignancy. Median SBRT dose was 50 Gy (range, 30 to 55 Gy) in a median of 5 fractions (range, 3 to 10 fractions) with static field SBRT or volumetric modulated arc therapy. Median follow-up is 16.7 months. Primary tumors had a median longest dimension on the original CT of 1.6 cm (range, 0.5 to 3.3 cm) and posttreatment CT scan of 1.25 cm (range, 0.0 to 4.5 cm) (P=0.025). Median pretreatment standard uptake value on initial PET scan is 4.6 mg/mL (range, 0.0 to 16.2 mg/mL), and at a median of 7.6 months after SBRT, decreased to 2.25 mg/mL (range, 0.0 to 10.9 mg/mL) on posttreatment PET (P=0.002). Crude local control is 97.1%. The estimated 2-year regional control is 80%, distant control 85%, and overall survival 85%. There were no grade 3 or greater acute toxicities and only 3 grade 3 chronic treatment-related toxicitities. In medically inoperable patients with unbiopsied lung cancer, local control can be achieved with minimal toxicity with the use of SBRT. The use of SBRT for unbiopsied early-stage lung cancer patients should be performed in a multidisciplinary setting and after detailed discussion with the patient about the risks and benefits of SBRT.

Decreased Brain FDG Uptake in Patients with Diffuse Large B Cell Lymphoma (cold brain) Is Associated with High Risk Disease and Predicts Poor Response to R-CHOP Chemotherapy

Abstract 1593 Background: Decreased 2-deoxy-2-(18F)fluoro-D-glucose (FDG) uptake by brain tissue, (henceforth “cold brain”) has been occasionally described in the literature in patients with bulky solid tumors. There is currently no data describing brain FDG uptake on positron emission tomography (PET) scan in patients with diffuse large B cell lymphoma (DLBCL) and its association with clinical characteristics as well as prognosis. Method: We retrospectively analyzed clinical data from 110 patients with histologically confirmed DLBCL diagnosed between November 1, 2004 and December 31, 2011. Initial staging PET scans prior to treatment were reviewed. Brain FDG uptake on PET scan was analyzed by an expert nuclear radiologist. Qualitative determination of cold versus normal brain activity was made relative to usual distribution and metabolism. Secondarily, a region of interest cursor was placed on the right basal ganglia for a quantitative standard uptake value (SUV) measurement. In cases where measurement of the right basal ganglia was not possible, the cerebellum was used. Patient characteristics were compared using Fisher's exact test. Survival analyses were performed using Kaplan-Meier curves and compared using log-rank test. Cox proportional regression model was used for multivariate analyses. Results: We included 110 patients in the study. Twenty patients (18%) had cold brain by initial PET scan. The cold brain subgroup had a median age of 72.5 years (range, 46 to 85) and 55.0% were males. Cold brain was associated with higher rates of stage III/IV disease (80.0% vs 52.2%; P = 0.026), International Prognostic Index (IPI) score of ≥3 (85.2% vs. 36.7%; P = 0.0001), and > 1 extranodal sites of involvement (50.0% vs. 26.7%; P = 0.059) compared to the non-cold brain subgroup. Among patients who received rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy (R-CHOP), those with cold brain had a lower complete response rate (44.0% vs. 86.0%; P = 0.030), shorter progression-free-survival (PFS) (4.5 months vs. 9.1 months; P = 0.06), but similar overall survival (OS) (47.9 months vs. 58.4 months; P = 0.26). After adjusting for IPI, patients with cold brain seemed to have a shorter PFS compared to those without cold brain, although this was not statistically significant (hazard ratio: 3.13; 95% CI: 8.20-1.22; P = 0.096). Conclusion: In our study, cold brain was a phenomenon frequently observed among patients with newly diagnosed DLBCL. It was associated with higher risk disease, lower complete response rate to R-CHOP chemotherapy, and potentially shorter PFS. Further studies in larger patient population are needed to determine its true prognostic significance. Disclosures: No relevant conflicts of interest to declare.

Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment–dementia converters measured by positron emission tomography with [11C]DAA1106

Subjects with mild cognitive impairment (MCI) have “prodromal or incipient” dementia with neuropathological changes. Peripheral benzodiazepine receptor (PBR) binding was shown to reflect activated microglia, one of the predictive biomarkers of conversion to dementia. We sought to evaluate PBR binding in MCI subjects using positron emission tomography (PET). PET scans with [11C]DAA1106, a potent and selective ligand for PBR, were performed on seven MCI subjects, 10 patients with Alzheimer's disease (AD) and 10 age-matched control subjects. PBR binding in the regions of interest was quantified by binding potential (BP). Five MCI subjects were clinically followed for 5years after their initial PET scans. [11C]DAA1106 binding to PBR was significantly increased in widespread areas in MCI subjects when compared to healthy controls. We found no significant difference in BP between MCI and AD patients. MCI subjects with [11C]DAA1106 binding values higher than the control mean +0.5 standard deviation (S.D.) developed dementia within 5years. Our finding of higher DAA binding in MCI subjects indicated that microglial activation may occur before the onset of dementia. In vivo detection of microglial activation may provide useful prognostic information with respect to stratifying MCI subjects at increased risk of dementia.

Use of Laxative-augmented Contrast Medium in the Evaluation of Colorectal Foci at FDG PET

To compare the diagnostic accuracy of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection of colon lesions with that of delayed PET/computed tomography (CT) performed after the administration of a laxative-augmented contrast medium. All patients gave written informed consent according to the guidelines issued by the institutional review board. In a prospective study performed from November 2005 to December 2006, images obtained in 847 patients were reviewed by two physicians in consensus. Colorectal FDG uptake on initial PET images that exceeded background FDG accumulation was graded as minimal, equivocal, or positive. When the initial PET scan revealed a colorectal region of increased uptake, either oral or anal laxative-augmented contrast medium was administered on the basis of the site of colorectal FDG focus and delayed PET/CT was performed. Initial PET findings were reevaluated and revised when necessary. Comparison was performed on a per-patient basis. Findings at histopathologic analysis and clinical follow-up served as the reference standard. The accuracy of PET was compared with that of PET/CT by using the McNemar test. Colorectal FDG foci were seen on initial images in 137 patients. Uptake on the initial images was reported as minimal in 14 patients, equivocal in 68, and positive in 55. With use of a laxative-augmented contrast medium and delayed PET/CT, the proportions of equivocal and positive results decreased by 84% (57 of 68 patients) and 58% (18 of 31 patients), respectively. The accuracy of delayed PET/CT in the depiction of colorectal cancer was greater than that of initial PET (93.4% [128 of 137 patients] vs 71.5% [98 of 137 patients], respectively; P < .01). Delayed PET/CT with laxative-augmented contrast medium is more accurate than initial PET alone in the detection of colorectal cancer. This approach has promise as a tool for guiding decisions about how to treat patients with colorectal FDG foci. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101193/-/DC1.

Outcomes of Positron Emission Tomography–Staged Clinical N3 Breast Cancer Treated With Neoadjuvant Chemotherapy, Surgery, and Radiotherapy

To evaluate the treatment outcome and efficacy of regional lymph node irradiation after neoadjuvant chemotherapy (NCT) and surgery in positron emission tomography (PET)-positive clinical N3 (cN3) breast cancer patients. A total of 55 patients with ipsilateral infraclavicular (ICL), internal mammary (IMN), or supraclavicular (SCL) lymph node involvement in the absence of distant metastases, as revealed by an initial PET scan, were retrospectively analyzed. The clinical nodal stage at diagnosis (2002 AJCC) was cN3a in 14 patients (26%), cN3b in 12 patients (22%), and cN3c in 29 patients (53%). All patients were treated with NCT, followed by mastectomy or breast-conserving surgery and subsequent radiotherapy (RT) with curative intent. At the median follow-up of 38 months (range, 9-80 months), 20 patients (36%) had developed treatment failures, including distant metastases either alone or combined with locoregional recurrences that included one ipsilateral breast recurrence (IBR), six regional failures (RF), and one case of combined IBR and RF. Only 3 patients (5.5%) exhibited treatment failure at the initial PET-positive clinical N3 lymph node. The 5-year locoregional relapse-free survival, disease-free survival (DFS), and overall survival rates were 80%, 60%, and 79%, respectively. RT delivered to PET-positive IMN regions in cN3b patients and at higher doses (≥55 Gy) to SCL regions in cN3c patients was not associated with improved 5-year IMN/SCL relapse-free survival or DFS. NCT followed by surgery and RT, including the regional lymph nodes, resulted in excellent locoregional control for patients with PET-positive cN3 breast cancer. The primary treatment failure in this group was due to distant metastasis rather than RF. Neither higher-dose RT directed at PET-positive SCL nodes nor coverage of PET-positive IMN nodes was associated with additional gains in locoregional control or DFS.

Usefulness of 3′-[F-18]Fluoro-3′-deoxythymidine with Positron Emission Tomography in Predicting Breast Cancer Response to Therapy

The usefulness of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) in monitoring breast cancer response to chemotherapy has previously been reported. Elevated uptake of FDG by treated tumors can persist however, particularly in the early period after treatment is initiated. 3'-[F-18]Fluoro-3'-deoxythymidine (FLT) has been developed as a marker for cellular proliferation and, in principle, could be a more accurate predictor of the long-term effect of chemotherapy on tumor viability. We examined side-by-side FDG and FLT imaging for monitoring and predicting tumor response to chemotherapy. Fourteen patients with newly diagnosed primary or metastatic breast cancer, who were about to commence a new pharmacologic treatment regimen, were prospectively studied. Dynamic 3-D PET imaging of uptake into a field of view centered over tumor began immediately after administration of FDG or FLT (150 MBq). After 45 minutes of dynamic acquisition, a clinically standard whole-body PET scan was acquired. Patients were scanned with both tracers on two separate days within one week of each other (1) before beginning treatment, (2) two weeks following the end of the first cycle of the new regimen, and (3) following the final cycle of that regimen, or one year after the initial PET scans, whichever came first. (Median and mean times of early scans were 5.0 and 6.6 weeks after treatment initiation; median and mean times for late scans were 26.0 and 30.6 weeks after treatment initiation.) Scan data were analyzed on both tumor-by-tumor and patient-by-patient bases, and compared to each patient's clinical course. Mean change in FLT uptake in primary and metastatic tumors after the first course of chemotherapy showed a significant correlation with late (av. interval 5.8 months) changes in CA27.29 tumor marker levels (r = 0.79, P = 0.001). When comparing changes in tracer uptake after one chemotherapy course versus late changes in tumor size as measured by CT scans, FLT was again a good predictor of eventual tumor response (r = 0.74, P = 0.01). Tumor uptake of FLT was near-maximal by 10 minutes after injection. The time frame five to 10 minutes postinjection of FLT produced standardized uptake value (SUV) values highly correlated with SUV values obtained after 45-minute uptake (r = 0.83, P < 0.0001), and changes in these early SUVs after the first course of chemotherapy correlated with late changes in CA27.29 (r = 0.93, P = 0.003). A 10-minute FLT-PET scan acquired two weeks after the end of the first course of chemotherapy is useful for predicting longer-term efficacy of chemotherapy regimens for women with breast cancer.

Reduction of Brown Fat 2-Deoxy-2-[F-18]fluoro-d-glucose Uptake by Controlling Environmental Temperature Prior to Positron Emission Tomography Scan

Brown fat uptake of 2-deoxy-2-[F-18]fluoro-D: -glucose (FDG) on a positron emission tomography (PET) scan limits the ability to assess for cancer. Drugs such as benzodiazepine, propranolol, and reserpine have been proposed to reduce this uptake, but the studies have been either small clinical or preclinical trials. As an alternative, we evaluated the effect of controlling the patient's environmental temperature on brown fat uptake of FDG. From January 1, 2002 to November 30, 2004, patients were identified who had (1) a pattern of FDG uptake in the neck/paravertebral areas suggestive of brown fat, (2) a repeat FDG-PET scan after control of the patient's environmental temperature, and (3) no evidence of cancer in the neck/paravertebral areas by other diagnostic methods. For the follow-up PET scan, all patients wore warm clothing and avoided exposure to cold air during their transit to our facility. After arrival, patients were kept in a separate temperature-controlled room (at least 75 degrees F) for 15 minutes to two hours before FDG injection as well as during the uptake phase. Four physicians blindly and retrospectively assessed the FDG uptake in the neck and paravertebral regions on all initial and temperature-controlled PET scans by visually grading the radioactivity on a semiquantitative scale (0 = background, 1+ = background but <liver, 2+ = equal to liver, 3+ >liver). The changes in maximal SUVs were determined in the left and right neck region. Data were evaluated using a two-tail t-test. Ten patients met the above criteria. The median age was 32 years with a range of 11-58 years. In comparing the semiquantitative uptake and the SUVs of FDG in the neck and paravertebral areas on the initial PET scan to the temperature-controlled PET scan, the mean decrease and the standard deviation of the decrease demonstrated a statistically significant decrease in with P values range from <0.02 to <0.001. Controlling the patient's environmental temperature prior to the dosing and during the uptake phase can significantly reduce FDG uptake in brown fat in the neck and paravertebral areas. Further studies are warranted to determine the most effective protocol to control the patient's environmental temperature in order to minimize brown fat uptake.

Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer.

A single institution study was undertaken to evaluate the role of positron emission tomography (PET) scans with fluorodeoxyglucose (FDG) prior to radiation and following radiation. Forty-five patients with head and neck cancers were evaluated with FDG-PET scans as well as either CT or MRI prior to treatment with definitive radiation (RT). These same scans were obtained following completion of RT at 1 month (36 patients), 4 months (28 patients), 12 months (19 patients), and 24 months (15 patients). Standard uptake values (SUV) normalized for blood glucose and lean body mass were calculated on the initial and 1-month post-treatment PET scans. Fifteen patients are alive without evidence of disease at 24 to 52 months following RT. Initial SUVs were calculated on the primary tumor site and ranged from 2.5 to 28.5. These values did not have any correlation with local control when examined for the entire group, primary site, or T stage. One-month post-RT SUV ranged from 1.8 to 6.24. Of the 36 1-month post-RT PET scans, six were interpreted as positive for residual disease and were confirmed by biopsy. Four of the five scans, which were interpreted as equivocal, were positive on biopsy. Seven of the 25 scans, which were interpreted as negative for tumor, were positive on biopsy. Four-month scans were more accurate for disease with disease noted in 0 of 18 negative scans, 6 of 7 positive scans, and 2 of 3 equivocal scans. PET is useful for initial imaging of head and neck cancers. SUV does not appear to be useful for predicting outcome following treatment with RT. One-month post-RT scans were inaccurate for predicting the presence of cancer. Four-month post-RT scans were a better predictor for the presence of cancer.

Correlations Between the Distribution of Cortical Hypometabolism and Clinical Manifestations in Patients with West Syndrome

Purpose: To examine the relation between the distribution of cortical hypometabolism and clinical manifestations in patients with West syndrome (WS). Methods: Serial positron emission tomography (PET) with [18]fluorodeoxyglucose was performed in 32 patients with WS, first at the onset of spasms and later at age 10 months or 3 months after the initial treatments. We excluded patients with diffuse or multiple abnormalities on magnetic resonance imaging (MRI). The age at onset of spasms ranged from 2 to 26 months, and ages at te end of follow‐up ranged from 2 to 6 years. Fifteen patients were diagnosed with cryptogenic WS and 17 with symptomatic WS. We classified the distribution of cortical hypometabolism into following groups: (A) occippitotemporal areas, (B) temporoparietal areas, (C) frontotemporal areas, (D) diffuse, and (E) none, or (a) unilateral and (b) bilateral. We compared the distribution of cortical hypometabolism with the age at onset of spasms, outcome of seizures, and psychomotor development. The presence of psychomotor retardation was determined by clinical observations and a low Tsumori‐Inage developmental quotient score (DQ &lt; 80). Chugani et al. reported that patients with bitemporal hypometabolism had poor developmental and seizure outcome, and that the majority were autistic. Therefore we particularly focused on patients with focal cortical hypometabolism in the temporal lobes bilaterally. Results: Initial PET scans demonstrated diffuse or focal hypometabolism in 24 patients. The second PET showed hypometabolism in only 10 of these patients. Hypometabolism was present on the second PET in two additional patients with normal PET findings at the onset of the disease. The number of patients with each distribution of hypometabohm at the first PET scan were as follows: six patients in group A, eight patients in B, five patients in C, five patients in D, and eight patients in E, or nine patients in group a and 15 patients in b. The mean age at onset of spasms in each group was 4.0 months in group A, 8.3 in B, 13.4 in C, 10.4 in D, and 4.8 in E, or 4.7 in group a, and 11.2 in b. The age at onset of spasms in patients with occipitotemporal hypometabolic areas was significantly lower than that in patients with frontotemporal hypometabolic areas. The age at onset of spasms in patients with unilateral hypometabolic areas was also significantly lower than that in those with bilateral hypometabolic areas. There were no significant correlations between the distributions of hypometabolism on the first scan and seizure outcome or psychomotor development. The existence of hypometabolic areas on the second PET scan was positively correlated with the poor developmental and seizure outcome. Nine patients had focal hypometabolism in bitemporal areas on the first scan. In five of these nine patients, hypometabolism disappeared on the second scan. The outcome of seizures and psychomotor development was poor in patients who had bitemporal hypometabolism after the initial treatment, as Chugani et al. reported. However, four of the five patients in whom bitemporal hypometabolism disappeared on the second scan had no epileptic seizures after the initial treatment and psychomotor development were almost normal. Conclusions: There was a correlation between the distribution of hypometabolic areas and the age at onset of spasms. It is possible that functional abnormality in the cerebral cortex undergoing maturational changes has an important role in the generation of infantile spasms. However, the cortical hypometabolism revealed by PET changes with clinical symptoms. To predict the outcome in WS, it is important to follow up the PET findings after the initial treatments.

Global aphasia due to thalamic hemorrhage: A case report and review of the literature

A 55-year-old patient was admitted with weakness in the right extremities and with significant language deficits. Both computed tomography (CT) and positron-emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose were done within 1 month and repeated at 10 months after onset. Language evaluation was done using parts of the Western Aphasia Battery (WAB) and the Boston Diagnostic Aphasia Examination (BDAE) at 1 month after admission, at 3 months, and at 10 months. The initial CT scan revealed hemorrhage in the left thalamus with edema surrounding the hemorrhage. A follow-up CT scan after 10 months showed an old hemorrhage in the left thalamus with no new lesions. The initial PET scan revealed hypometabolism in the left thalamus, and a repeat PET scan at 10 months showed reduced uptake in the left frontal, left parietal, and left temporal cortex. An initial language evaluation showed impaired auditory and reading comprehension, poor verbal expression, impaired repetition, and difficulty with naming and with sentence completion. The patient was diagnosed with global aphasia. Follow-up language evaluation at 3 months and 10 months showed only minimal improvement in his communication. Global aphasia due to lesions in the thalamic region is rare and the prognosis is poor.

Functional neuroanatomy of visually elicited simple phobic fear: Additional data and theoretical analysis

We investigated central nervous system correlates of simple phobic fear. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in eight volunteers with symptomatic spider phobia that were exposed to visual phobogenic and neutral stimuli. Diazepam (0.1 mg/kg body weight i.v.) or placebo was administered under double-blind conditions after initial PET scans. The PET scans were then repeated. The presence of fear was confirmed by rating procedures and increased number of nonspecific electrodermal fluctuations and by higher heart rate during phobic than during neutral stimulation. Phobic as compared to neutral stimulation elevated the regional to whole brain (relative) CBF in the secondary visual cortex but reduced relative rCBF in the hippocampus, prefrontal, orbitofrontal, temporopolar, and posterior cingulate cortex. Diazepam treatment did not affect the relative rCBF or the subjective or physiological fear indices. The observed rCBF pattern replicates our previous findings in snake phobics (M. Fredrikson et al. [1993] Psychophysiology, 30, 127-131; G. Wik et al. [1993] Psychiatry Research (Neuroimaging), 50, 15-24) and indicates that fear and anxiety affect cortical areas outside the classic limbic system areas.