Tau uptake in agrammatic primary progressive aphasia with and without apraxia of speech.

BACKGROUND AND PURPOSE: The non-fluent/agrammatic variant of primary progressive aphasia (agPPA) is a heterogeneous diagnosis wherein some individuals have apraxia of speech (AOS). When agPPA includes AOS, a tauopathy is the likely underlying pathology. Recently, [18F]AV-1451 was developed for the in-vivo assessment of tau. In this study, we compared patterns of tau tracer uptake in patients with agPPA with and without AOS. METHODS: Nine patients with agPPA (four without AOS) underwent tau positron emission tomography imaging with [18F]AV-1451. Uptake of [18F]AV-1451 was assessed as cortical to cerebellar crus ratio (standard uptake value ratio) in cortical regions of interest measured using the MCALT atlas and compared voxel-wise in SPM12. Each patient was age- and sex-matched to three controls. RESULTS: The agPPA without AOS showed uptake in the left frontal and temporal lobes, whereas agPPA with AOS showed uptake in the bilateral supplementary motor areas, frontal lobes, precuneus and precentral gyrus relative to controls. The left precentral gyrus had uptake in agPPA with AOS relative to those without AOS. CONCLUSIONS: This cross-sectional study suggests that [18F]AV-1451 uptake in the precentral gyrus is implicated in AOS in agPPA.

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

BACKGROUND AND OBJECTIVES: We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. METHODS AND RESULTS: Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. CONCLUSIONS: Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry.

Regional ß-amyloid burden does not correlate with cognitive or language deficits in Alzheimer's disease presenting as aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language impairment (aphasic AD). Our previous study demonstrated an association between global ß-amyloid burden measured on [(11)C] Pittsburgh compound B (PiB) positron emission tomography and general cognitive impairment, but not with aphasia, in such subjects. As a follow-up, whether there is any association between regional ß-amyloid burden, atrophy on magnetic resonance imaging (MRI) and global cognitive impairment, aphasia or other cognitive and functional impairment in aphasic AD is assessed. METHODS: Forty-four aphasic AD subjects who underwent PiB scanning and volumetric MRI and were determined to be positive for ß-amyloid deposition were analyzed. All had completed detailed neurological, neuropsychological and language batteries. Spearman's rank-order correlation was utilized to assess for associations. RESULTS: Greater visuospatial impairment was associated with increased ß-amyloid burden in the primary visual cortex (P = 0.001). Although there were many trends for associations between neurocognitive and language deficits and regional ß-amyloid burden, there were no strong associations that survived correction for multiple comparisons. However, neurocognitive and language impairment in these subjects strongly correlated with the degree of left lateral temporal and inferior parietal atrophy (P < 0.004). CONCLUSIONS: The findings from this study suggest a close relation between the severity of regional atrophy and cognitive and language impairment, but argue against a strong association between regional ß-amyloid burden and such deficits in aphasic AD subjects. Hence, other pathological factors may be driving the previously identified association between global ß-amyloid deposition and general cognitive impairment in aphasic AD.

Early detection of prostate cancer relapse by biochemistry and diagnostic imaging.

Prostate cancer (PCa) is a common malignancy in men associated with an increase in the incidence rate. Radical prostatectomy (RP) or external beam radiotherapy (EBRT) represents the most employed treatments for the local control of disease. However, 10-50% of patients who experienced a recurrence of disease after primary treatments can benefit from salvage or palliative therapies. To date, prostate specific antigen (PSA) is usually used in clinical practice to monitor the status of disease and to early detect the recurrence of PCa. Nevertheless, PSA cannot discriminate the presence of local vs. distant metastatic disease. Circulating tumor cells are considered as a sign of disease widespread, but their correlation with metastatic PCa and local recurrence of disease is still indeterminate. Digital rectal exploration and transrectal ultrasonography are considered the first clinical and diagnostic approach to identify the local recurrence of PCa, but are associated with a low detection rate and low diagnostic accuracies. Conversely, magnetic resonance imaging (MRI) has gained a great importance in this setting of disease, being able to determine the presence of local recurrence with high sensitivity, also in the presence of low serum PSA levels. Lastly, the introduction of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline agents let to improve the management of patients with early recurrence of disease, although its accuracy is linked to the PSA and PSA dynamic values. New radiopharmaceutical agents, like 68Ga-PSMA or 18F-FACBC and others could improve the diagnostic accuracy of PET/CT, but the data is still preliminary. In the present review we will discuss both clinical and diagnostic instrumentations, actually available in clinical practice, able to early identify the presence of recurrent PCa and to differentiate between local and distant relapse of tumor.

Amyloid burden correlates with cognitive decline in Alzheimer's disease presenting with aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language deficits. It is unclear whether the burden of underlying ß-amyloid pathology is associated with language or general cognitive impairment in these subjects. METHODS: The relationship between cortical ß-amyloid burden on [(11) C]Pittsburgh compound B (PiB) positron emission tomography (PET) and performance on the Montreal Cognitive Assessment (MoCA), the Wechsler Memory Scale - Third Edition (WMS-III), the Boston Naming Test (BNT) and the Western Aphasia Battery (WAB) was assessed using regression and correlation analyses in subjects presenting with aphasia who showed ß-amyloid deposition on PiB PET. RESULTS: The global PiB ratio was inversely correlated with MoCA (P = 0.02) and the WMS-III Visual Reproduction (VR) subtest (VR I, P = 0.02; VR II, P = 0.04). However, the correlations between PiB ratio, BNT (P = 0.13), WAB aphasia quotient (P = 0.11) and WAB repetition scores (P = 0.34) were not significant. CONCLUSION: This study demonstrates that an increased cortical ß-amyloid burden is associated with cognitive impairment, but not language deficits, in AD subjects presenting with aphasia. The results suggest that ß-amyloid deposition could be partly contributing to impaired cognition in such patients whilst language dysfunction may be more influenced by other pathological mechanisms, perhaps downstream pathways of ß-amyloid deposition.

A computational model of neurodegeneration in Alzheimer's disease.

Disruption of mental functions in Alzheimer's disease (AD) and related disorders is accompanied by selective degeneration of brain regions. These regions comprise large-scale ensembles of cells organized into systems for mental functioning, however the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and functional systems is not clear. Here we present a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques in two cohorts of patients with AD. This reflected a simple information processing-based functional description of macroscale brain anatomy which we link to AD physiology, functional networks, and mental abilities. We further apply the model to normal aging and seven degenerative diseases of mental functions. We propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology.

Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan.

OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation.

Corticobasal syndrome (CBS) is a phenotypic manifestation of diverse pathologies, including Alzheimer's disease and 4-repeat tauopathies. Predicting pathology in CBS is unreliable and, hence, molecular neuroimaging may prove to be useful. The aim of this study was to assess regional patterns of uptake on [18F] AV-1451 PET in CBS and determine whether patterns of uptake differ according to beta-amyloid deposition or differing clinical presentations. Fourteen patients meeting criteria for CBS underwent Pittsburgh Compound B (PiB) and [18F] AV-1451 PET. Seven patients presented as CBS and seven presented with apraxia of speech (AOS) and later evolved into CBS. A global PiB summary was calculated and used to classify patients as PiB (-) or PiB (+). AV-1451 uptake was calculated in fourteen regions-of-interest, with values divided by uptake in cerebellar crus grey matter to generate standard uptake value ratios. AV-1451 uptake was considered elevated if it fell above the 95th percentile from a group of 476 cognitively unimpaired normal controls. Six of the 14 CBS patients (43%) were PiB (+), with three of these patients showing strikingly elevated AV-1451 uptake across many cortical regions. Of the eight PiB (-) patients, only those with AOS showed elevated AV-1451 uptake in supplementary motor area and precentral cortex compared to controls. No region of elevated AV-1451 uptake were observed in PiB (-) typical CBS patients without AOS. These results suggest that regional [18F] AV-1451 is variable in CBS and depends on the presence of beta-amyloid as well as clinical presentation such as AOS. PiB (+) CBS does not necessarily reflect underlying Alzheimer's disease; however, the possibility some of these patients will evolve into Alzheimer's disease over time cannot be excluded.

Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.

MV-NIS is an Edmonston lineage oncolytic measles virus expressing the human sodium iodide symporter-a means for monitoring by non-invasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide 2 days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to four dose levels without reaching maximum tolerated dose (MTD) and subsequently to two higher dose levels when improved virus manufacture technology made it possible. MTD was not reached in Cohort 1, and TCID50 1011 is the dose being used in a Phase II trial of single agent MV-NIS. Grade 3-4 adverse events in both cohorts at all dose levels were: neutropenia (n=9); leukocyte count decreased (n=5); thrombocytopenia (n=2); and CD4 lymphocytes decreased, anemia and lymphopenia (each n=1). MV-N RNA sequences were amplified from gargle specimens, blood and urine. 123I scans were positive in eight patients. One patient achieved a complete response; transient drops in serum free light chains were seen in other patients. MV-NIS is capable of replicating before being cleared by the immune system. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated myeloma.

Surveillance for recurrent head and neck cancer using positron emission tomography.

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.

Prospective investigation of positron emission tomography in lung nodules.

PURPOSE: Solitary pulmonary nodules (SPNs) are commonly identified by chest radiographs and computed tomography (CT). Biopsies are often performed to evaluate the nodules further. An accurate, noninvasive diagnostic test could avoid the morbidity and costs of invasive tissue sampling. We evaluated the ability of fluorine-18 deoxyglucose positron emission tomography (FDG-PET) to discriminate between benign and malignant pulmonary nodules in a prospective, multicenter trial. METHODS: Eighty-nine patients who had newly identified indeterminate SPNs on chest radiographs and CT were evaluated with FDG-PET. PET data were analyzed semiquantitatively by calculating standardized uptake values (SUVs) as an index of FDG accumulation and also by a visual scoring method. PET results were compared with pathology results. RESULTS: Sixty SPNs were malignant and 29 were benign. Using SUV data, PET had an overall sensitivity and specificity for detection of malignant nodules of 92% and 90%. Visual analysis provided a slightly higher, but not statistically significant, sensitivity of 98% and lower specificity of 69%. For SPNs < or = 1.5 cm (34 of 89), the sensitivity and specificity of SUV and visual analysis were 80% and 95% and 100% and 74%, respectively. CONCLUSION: FDG-PET can accurately characterize indeterminate SPNs. PET imaging provides a noninvasive method to evaluate indeterminate SPNs, which can reduce the need for invasive tissue biopsy.

Naltrexone vs. nefazodone for treatment of alcohol dependence. A placebo-controlled trial.

This study compared the effects of nefazodone, a serotonergic antidepressant, with the opioid antagonist naltrexone, and an inactive placebo in 183 alcohol-dependent subjects receiving weekly relapse prevention psychotherapy. Following a single-blind, placebo lead-in period, subjects were randomly assigned to receive study medication, which they took under double-blind conditions for 11 weeks. Naltrexone treatment was associated with significantly more adverse neuropsychiatric and gastrointestinal effects, poorer compliance, and a greater rate of treatment attrition. There were no reliable between-group differences in drinking behavior. These results indicate that nefazodone is not efficacious for treatment of alcohol dependence. Furthermore, the clinical utility of naltrexone seems to be limited by its adverse effects, a finding that has important implications for efforts to develop medications to treat alcohol dependence.

Synthesis and antimuscarinic activity of some 1-cycloalkyl-1-hydroxy-1-phenyl-3-(4-substituted piperazinyl)-2-propanones and related compounds.

A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. The objective of this study was to derive new antimuscarinic agents with potential utility in treating urinary incontinence associated with bladder muscle instability. These compounds were examined for M1, M2, and M3 muscarinic receptor selectivity in isolated tissue assays and for in vivo effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. Potency and selectivity in these assays were influenced most notably by the nature of the substituent group on the terminal nitrogen of the piperazine moiety. Benzyl substitution was particularly advantageous in producing compounds with functional M3 receptor (smooth muscle) and bladder selectivity; it provided several candidates for clinical study. In vivo, 3-(4-benzyl-piperazinyl)-1-cyclobutyl-1-hydroxy-1-phenyl-2-propanone (24) demonstrated 11- and 37-fold separations in its effect on bladder function versus mydriatic and salivation responses, respectively. The corresponding 2-chlorobenzyl derivative 25 was more than 178-fold selective for M3 versus M1 and M2 muscarinic receptors. 3-(4-Benzylpiperazinyl)-1,1-diphenyl-1-hydroxy-2-propanone (51) was 18-fold selective for M3 versus M1 and 242-fold selective for M3 versus M2 receptors. It was also selective in guinea pigs, where it displayed 20- and 41-fold separations between bladder function and effect on mydriasis and salivation, respectively. In general, the results of this study are consistent with the proposition that the described piperazinylpropanones interact with muscarcinic receptors in a hydrogen-bonded form that presents a conformation similar to that apparently adopted by classical antimuscarinic agents.

Synthesis and antimuscarinic properties of some N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones.

In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones, conformationally-constrained lactone relatives of benactyzine, was prepared. The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The separate and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized molecular cloned subpopulations. In this article, structure-activity relationships for the series of substituted lactones are discussed. These studies led to the identification of (R)-[(2-isopropyl-1H-imidazol-1-yl)methyl]-4,5-dihydro-3,3-diphenyl-2(3H )- furanone (23) as a clinical candidate for treating urinary bladder dysfunction.

Cardiac phantom evaluation of simultaneously acquired dual-isotope rest thallium-201/stress technetium-99m SPECT images.

Simultaneously acquired dual-isotope 201Tl/99mTc SPECT studies were performed using cardiac and thoracic phantoms to evaluate the dual-isotope myocardial perfusion technique. Cardiac phantom images representing infarction, viable myocardium and various levels of ischemia were analyzed. Studies with and without attenuating media were performed, and myocardium-to-defect count ratios and defect sizes from dual-isotope SPECT images were compared to myocardium-to-defect count ratios and defect sizes from single-isotope (201Tl and 99mTc) SPECT images. Dual-isotope studies also were interpreted qualitatively. Studies with background activity simulating clinical conditions were performed and interpreted qualitatively. Myocardium-to-defect count ratios from both 99mTc and 201Tl were similar in single-isotope and dual-isotope SPECT images. Thallium-201 and 99mTc defect sizes were decreased slightly (mean +/- s.d., 1.0 +/- 1.7 cc for 201Tl and 0.7 +/- 1.0 cc for 99mTc) on dual studies when compared to single studies but were not statistically significant. Dual-isotope image simulations of normal, ischemic and infarcted and viable myocardium were correctly identified by experienced clinicians in 95% of the cases (21/22). Simultaneous dual-isotope 201Tl/99mTc SPECT imaging of cardiac phantoms produced images that had similar myocardium-to-defect count ratios to those produced using single-isotope techniques and were correctly evaluated on qualitative analysis. Changes in defect size related to dual-isotope imaging were minimal and not qualitatively important.

Optimum scanning protocol for FDG-PET evaluation of pulmonary malignancy.

UNLABELLED: FDG-PET can differentiate benign from malignant focal pulmonary opacities. We performed dynamic FDG-PET studies to determine the optimum time for emission data acquisition. METHODS: Patients with focal pulmonary abnormalities demonstrated by biopsy to be malignant (n = 10) or benign (n = 4) were evaluated with dynamic FDG-PET. Dynamic PET data were acquired as sequential 5-min images for 2.5 hr. Radioactivity concentration measurements of the focal abnormality, a similar area in the opposite lung, and both lungs in the field of view were made throughout the period of acquisition. Standardized uptake ratios (SUR) of the lesions were calculated. SUR data and lesion-to-background ratios were plotted. The time that the SUR provided the maximum separation between benign and malignant masses after FDG administration was determined. RESULTS: The SUR values provided the greatest separation between benign and malignant abnormalities beginning at 50 min and no advantage was identified in imaging later. Achievement of a 4:1 lesion-to-background ratio occurred by 50 min in malignant lesions. CONCLUSION: The acquisition of the emission data used in the evaluation of pulmonary malignancy should begin approximately 50 min after FDG administration.

Semiquantitative and visual analysis of FDG-PET images in pulmonary abnormalities.

UNLABELLED: FDG PET images of the thorax can be analyzed semiquantitatively using standardized uptake ratios (SUR) or activity ratios between abnormal and normal tissue, or qualitatively by visual comparison of the abnormality to normal structures. Standardized uptake ratio evaluation of FDG PET images has been shown to accurately differentiate benign from malignant focal pulmonary abnormalities. The accuracy of activity ratios and visual analysis have not been evaluated. We therefore prospectively analyzed FDG PET images in patients with pulmonary abnormalities to evaluate differences in analytic schemes. METHODS: We evaluated 107 patients with an indeterminate focal abnormality on chest radiograph or CT with FDG PET between November 1991 and March 1993. The PET studies were evaluated using SUR, activity ratios and visual analysis. Activity ratios of maximum activity/cc and average activity/cc between regions of interest (ROIs) in abnormalities and normal lung on the contralateral side were calculated. Visual interpretations were graded on a five-point scale of two observers' confidence of malignancy. FDG uptake in the abnormality was also visually graded in comparison to mediastinal activity. Receiver-operating characteristic (ROC) curve areas were generated for the SUR data, activity ratios and visual analysis. RESULTS: Of 88 patients in which a conclusive diagnosis was made, 61 (69%) patients had malignancy and 27 (31%) patients had a benign process. SUR, maximum activity ratio, average activity ratio and visual interpretation ROC curve areas were 0.96, 0.95, 0.92 and 0.96, respectively. CONCLUSIONS: SUR, activity ratios and visual evaluation are each equally accurate methods of FDG PET data analysis in differentiating malignant from benign focal pulmonary abnormalities.

Thoracic nodal staging with PET imaging with 18FDG in patients with bronchogenic carcinoma.

PURPOSE: To assess the role of positron emission tomographic (PET) imaging with 18-fluoro-2-deoxyglucose (18FDG) in detecting thoracic lymph node metastases in patients with bronchogenic carcinoma. MATERIALS AND METHODS: Over a 2-year period, any patient presenting to our institution with newly diagnosed bronchogenic carcinoma who was to have thoracic nodes sampled was considered eligible. All PET studies were performed prior to nodal sampling and areas of increased uptake were mapped according to the American Thoracic Society classification. Studies were correlated with CT and pathology. Sensitivity and specificity for predicting nodal metastases was calculated. RESULTS: Forty-two patients had 62 nodal stations (40 hilar/lobar, 22 mediastinal) sampled. The sensitivity and specificity for hilar/lobar lymph node station metastases using PET imaging was 73% and 76%, respectively. With CT, the sensitivity and specificity were 27% and 86%. The sensitivity and specificity using PET imaging for mediastinal node station metastases was 92% and 100%, respectively, while with CT the figures were 58% and 80%. The sensitivity and specificity for combined thoracic nodal station metastases using PET imaging was 83% and 82%, respectively, while with CT it was 43% and 85%. There was a strong statistical relationship between positive PET imaging and lymph node abnormalities. CONCLUSIONS: 18FDG-PET imaging is accurate in detecting thoracic lymph node metastases in patients with bronchogenic carcinoma. Normal results of PET studies virtually preclude the need for mediastinal nodal sampling prior to surgery, whereas abnormal results of studies most likely represent mediastinal metastases. Treatment can be based on the extent of disease suggested by PET imaging.

Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET).

Positron emission tomography (PET), with the glucose analog F-18 fluoro-deoxyglucose (FDG), takes advantage of the enhanced glucose uptake observed in neoplastic cells. We examined whether the detection of preferential FDG uptake with PET permits differentiation between benign and malignant focal pulmonary lesions in patients with suspected primary or recurrent lung cancer. Between November 1991 and September 1993, 100 patients with indeterminate focal pulmonary abnormalities including 16 patients who had previous lung resections for cancer were prospectively studied. Tissue diagnosis was obtained by transbronchial or percutaneous biopsy (n = 49) and open biopsy or resection (n = 35). Three patients underwent extended observation (> 2 years) alone. Excluded were 13 patients lacking firm pathologic diagnoses and less than 2-year follow-up. FDG activity in the lesion was expressed as a calculated standardized uptake ratio. Mean standardized uptake ratio (+/- standard deviation) was 6.6 (+/- 3.1) in 59 patients with cancer versus 2.0 (+/- 1.6) in 28 with benign disease (p = 0.0001; unpaired t test, two-sided). With a standardized uptake ratio > or = 2.5 used for detecting malignancy, sensitivity, specificity, and accuracy were 97% (57/59), 82% (23/28), and 92% (80/87), respectively. Notably, in patients evaluated for pulmonary abnormalities after lung resection for cancer, all chest recurrences were correctly identified. The exceptional sensitivity of FDG PET demonstrates that malignant pulmonary lesions preferentially accumulate FDG, which results in a standardized uptake ratio > or = 2.5. PET may be useful for distinguishing recurrent tumor from postoperative, or postradiation, changes. If performed in all patients before open biopsy, PET increases the diagnostic yield by reducing the number of patients who have benign lesions at operation. Moreover, by lowering expenditures for hospitalization and other diagnostic procedures, FDG PET may significantly reduce health care costs.

Positron emission tomography in lung cancer.

Reports on positron emission tomography have become more common in the oncology literature. After a short introduction to positron emission tomography, this review will look at the data relating to the use of this technology in the diagnosis, the staging, and the post-treatment evaluation of patients with lung cancer and will discuss its potential role in these evaluations.