Where Should I Draw the Line: PET-Driven, Data-Driven, or Manufacturer Cut-Off?

Background: The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial. Objective: To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement between 11C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aß1-42, pTau, tTau, and Aß1-42/Aß1-40 ratio) in our population, called PET-driven; an unbiased cut-off using data from a healthy research cohort, called data-driven, and that provided by the manufacturer. We also compare changes in ATN classification. Methods: CSF biomarkers measured by the LUMIPULSE G600II platform and qualitative visualization of amyloid positron emission tomography (a-PET) were performed in all the patients. We established a cut-off for each single biomarker and Aß1-42/Aß1-40 ratio that optimized their agreement with a-PET using ROC curves. Sensitivity, Specificity, and Overall Percent of Agreement are assessed using a-PET or clinical diagnosis as gold standard for every cut-off. Also, we established a data-driven cut-off from our cognitively unimpaired cohort. We then analyzed changes in ATN classification. Results: One hundred and ten patients were recruited. Sixty-six (60%) were a-PET positive. PET-driven cut-offs were: pTau > 57, tTau > 362.62, Aß1-42/Aß1-40 < 0.069. For a single biomarker, pTau showed the highest accuracy (AUC 0.926). New PET-driven cut-offs classified patients similarly to manufacturer cut-offs (only two patients changed). However, 20 patients (18%) changed when data-driven cut-offs were used. Conclusions: We established our sample's best CSF biomarkers cut-offs using a-PET as the gold standard. These cut-offs categorize better symptomatic subjects than data-driven in ATN classification, but they are very similar to the manufacturer's.

The role of PSMA radioligands in the diagnosis and treatment of prostate carcinoma.

Prostate cancer (PC) is the most common tumor in men in the West and the fifth leading cause of cancer-related death. The use of PSMA radioligands has represented an important advance both in its diagnosis, through PET molecular imaging, and in its treatment in advanced stages of the disease. This article reviews the contribution of PET studies with PSMA radioligands in initial staging, in tumor detection in biochemical recurrence (elevation of PSA) after treatment with curative intent, and in the more advanced stages of the disease (castration resistant PC or CRPC). The contribution of PSMA radioligand therapy (PSMA-RLT) in CRPC patients who progress to standard therapy is also analyzed.

Evaluation of choroidal thickness in prodromal Alzheimer's disease defined by amyloid PET.

OBJECTIVE: To assess and compare the involvement of choroidal thickness (CT) in patients with mild cognitive impairment (MCI) and dementia due to Alzheimer's disease (AD) defined by amyloid PET and healthy controls (HC). METHODS: Sixty-three eyes from 34 AD patients [12 eyes (19.0%) with dementia and 51 eyes (80.9%) with MCI], positive to 11C-labelled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired HC were recruited. All participants underwent enhanced depth imaging optical coherence tomography (EDI-OCT) assessing CT at 14 measurements from 2 B-scans. Paired Student t-test was used to compare CT measurements between MCI, dementia and sex- and age-paired HC. A univariate generalized estimating equations model (GEE) test was performed to compare MCI and dementia individually with all HC included. RESULTS: Compared with HC, eyes from patients with positive 11C-PiB PET/CT showed a significant CT thinning in 5 selected locations (in foveal thickness in vertical scan, in temporal scan at 1500µm, in superior scan at 500µm and in inferior scan at 1000µm and 1500µm, p = 0.020-0.045) whilst few significant CT reduction data was reported in MCI or dementia individually versus HC. However, the GEE test identified significant CT thinning in AD compared with all HC included (p = 0.015-0.046). CONCLUSIONS: To our knowledge, the present study is the first measuring CT in eyes from MCI and dementia eyes positive to 11C-PiB PET/CT reporting a significant trend towards CT thinning in MCI patients which became more pronounced in dementia stage. We support further investigation involving larger and prospective OCT studies in AD population characterized with available biomarkers to describe whether choroidal vascular damage occurs specifically in prodromal stages of AD.

A snake that bites its own tail. Acquisition and loss of concepts in children and semantic dementia patients through the analysis of drawings.

OBJECTIVE: The structure of the semantic network is constructed and organized during childhood development. Previous publications have hypothesized that neurodegenerative diseases would lead to a disruption of this network reversing the steps acquired in childhood. Semantic Dementia (SD) is a subtype of frontotemporal lobe degeneration in which the main symptom is a specific loss of semantic memory. We aimed to describe the sequential acquisition of concepts in 3-8 years old children evaluated through the production of drawings and, in parallel, their progressive loss in SD patients. METHODS: 104 children between 40 and 96 months categorized into tertiles according to their age, 21 SD patients categorized into tertiles according to their score on a category fluency task and 34 healthy volunteers were asked to draw 12 items with, a priori, different age of acquisition and familiarity, belonging to four different semantic categories. We employed the drawings of the healthy volunteers to build a scoring scheme. We considered that a concept was acquired in children when 50% or more of its features were present in their drawings, and it was lost in patients when more than 50% were missing. RESULTS: Those concepts which the children were able to acquire earlier, according to our scoring scheme, tended to remain in patients with more advanced SD. While the items that children acquired later, were, in general, those that the SD patients lost at earlier disease stages. CONCLUSION: The patterns of concept acquisition in children were the mirror image of the loss in patients with SD. Our study supports the hypothesis that the sequence of concept acquisition in childhood is reversed in SD patients.

Cognitive and Behavioral Profiles of Left and Right Semantic Dementia: Differential Diagnosis with Behavioral Variant Frontotemporal Dementia and Alzheimer's Disease.

BACKGROUND: Semantic dementia (SD) is a subtype of frontotemporal dementia (FTD) characterized by semantic memory loss and preserved abilities of other cognitive functions. The clinical manifestations of SD require a differential diagnosis with Alzheimer's disease (AD), especially those with early onset, and behavioral variant FTD (bvFTD). OBJECTIVE: The present study aimed to compare cognitive performances and neuropsychiatric symptoms in a population of AD, bvFTD, and left and right SD defined with the support of molecular imaging (amyloid and 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography) and assessed the accuracy of different neuropsychological markers in distinguishing these neurodegenerative diseases. METHODS: Eighty-seven participants (32 AD, 20 bvFTD, and 35 SD (17 Left-SD and 18 Right-SD) completed a comprehensive neuropsychological battery that included memory, language, attention and executive functions, visuospatial function, visuoconstructional skills, and tasks designed specifically to evaluate prosopagnosia and facial emotions recognition. The Neuropsychiatric Inventory was administered to assess neuropsychiatric symptoms. RESULTS: An episodic memory test that included semantic cues, a visuospatial test (both impaired in AD), a naming test and a prosopagnosia task (both impaired in SD) were the four most valuable cognitive metrics for the differential diagnosis between groups. Several behavioral abnormalities were differentially present, of which aggression, self-care (both more frequent in bvFTD), and eating habits, specifically overeating and altered dietary preference (more frequent in SD), were the most valuable in group discrimination. CONCLUSION: Our study highlights the value of a comprehensive neuropsychological and neuropsychiatric evaluation for the differential diagnosis between FTD syndromes and AD.

Ganglion cell layer thinning in prodromal Alzheimer's disease defined by amyloid PET.

INTRODUCTION: The objective of this study was to investigate and compare optic nerve and retinal layers in eyes of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) with paired control eyes using optical coherence tomography. METHODS: Sixty-three eyes of 34 subjects, 12 eyes with AD and 51 eyes with MCI, positive to 11C-labeled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired control eyes underwent optical coherence tomography scanning analyzing retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), Bruch's membrane opening-minimum rim width (BMO-MRW), inner plexiform layer (IPL), outer nuclear layer, and lamina cribrosa (LC). RESULTS: Compared with healthy controls, eyes of patients with positive 11C-PiB PET/CT showed a significant thinning of RNFL (P < .028) and GCL (P < .014). IPL and outer nuclear layer also showed significant thinning in two (P < .025) and one location (P < .010), respectively. No significant differences were found when optic nerve measurements BMO-MRW and LC were compared (P > .131 and P > .721, respectively). Temporal sector GCL, average RNFL, and temporal sector RNFL also exhibited significant thinning when MCI and control eyes were compared (P = .015, P = .005 and P = .050, respectively), and also the greatest area under the curve values (0.689, 0.647, and 0.659, respectively). GCL, IPL, and RNFL tend to be thinner in the AD group compared with healthy controls. DISCUSSION: Our study suggests that RNFL and GCL are useful for potential screening in the early diagnosis of AD. LC and BMO-MRW appear not to be affected by AD.

A Brief Drawing Task for the Differential Diagnosis of Semantic Dementia.

BACKGROUND: Semantic dementia (SD) is a subtype of frontotemporal lobe degeneration characterized by semantic loss, with other cognitive functions initially preserved. SD requires differential diagnosis with Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Semantic knowledge can be evaluated through different tests; however, most of them depend on language. OBJECTIVE: We describe the development of a brief drawing task that may be helpful for the differential diagnosis of SD. METHODS: Seventy-two patients, including 32 AD, 19 bvFTD, and 21 SD were asked to draw 12 items with different age of acquisition and familiarity, belonging to four different semantic categories. We employed the drawings of healthy volunteers to build a scoring scheme. RESULTS: Turtle, strawberry, train, and envelope were the items of each category that best discriminated between groups and were selected for the Brief drawing task. The discriminatory power of the Brief drawing task between SD versus AD and bvFTD patients, estimated through the area under the curve was 0.84 (95% CI = 0.72-0.96, p = 0.000007). In a logistic model, the Brief drawing task (p = 0.003) and VOSP "number location" subtest (p = 0.016) were significant predictors of the diagnosis of SD versus AD and bvFTD after adjustment by the main covariates. The Brief drawing task provided clinically useful qualitative information. SD drawings were characterized by loss of the distinctive features, intrusions, tendency to prototype, and answers like "I don't know what this is". CONCLUSION: The Brief drawing task appears to reveal deficits in semantic knowledge among patients with SD that may assist in the differential diagnosis with other neurodegenerative diseases.

A 5-year longitudinal evaluation in patients with mild cognitive impairment by 11C-PIB PET/CT: a visual analysis.

OBJECTIVE: The aim of this study was to evaluate the cerebral amyloid distribution in patients with mild cognitive impairment (MCI), assessed by carbon-11-Pittsburgh compound B (C-PIB) PET/CT, after 5 years of follow-up. PATIENTS AND METHODS: Ten amnestic MCI (A-MCI) and four nonamnestic (NA-MCI) patients were studied by C-PIB PET/CT and re-evaluated 5 years later by a new C-PIB PET/CT. PET/CT scans were acquired 60-90 min after the administration of 555 MBq C-PIB and analyzed visually, to obtain a score of the cerebral cortical C-PIB retention in the frontal, basal ganglia (BG), temporoparietal (TP), occipital, posterior cingulate, and cerebellum areas. Initial and 5-year follow-up C-PIB retentions were compared. RESULTS: Initially, 9/10 A-MCI patients were C-PIB positive and one was C-PIB negative. All four NA-MCI patients were C-PIB negative. Of the C-PIB-positive A-MCI patients, seven progressed to Alzheimer's disease dementia (AD-D), one to mixed dementia and one remained as A-MCI. The C-PIB-negative A-MCI patient remained as A-MCI. Of the four C-PIB-negative NA-MCI, one progressed to semantic dementia. All changes in C-PIB retention were of low intensity. The A-MCI patients who progressed to AD-D (n=7) showed an increase in C-PIB retention in the frontal (5/7), BG (3/7), TP (3/7), occipital (1/7), and posterior cingulate (1/7) regions. The A-MCI patient who progressed to mix dementia showed an increase in C-PIB retention in the frontal region. The C-PIB-positive A-MCI patient who remained as A-MCI showed an increase in C-PIB retention in the frontal, BG, and TP areas. The amyloid deposition in the anterior part of the brain (frontal, TP, and BG) increased more than that in the posterior part (occipital and precuneus) (7/9 vs. 2/9; P<0.05). CONCLUSION: PIB retention increased predominantly in the frontal, BG, and TP areas. C-PIB-positive A-MCI patients mostly progressed to AD-D, showing similar topographic changes in their cerebral C-PIB pattern than the patient who remained as A-MCI.

Effect of positive carbon-11-choline PET/CT results in the therapeutic management of prostate cancer biochemical relapse.

OBJECTIVE: Carbon-11-(C)-choline PET/computed tomography (CT) has shown good results in re-staging of prostate cancer (PCa) with raised serum levels of prostate-specific antigen. Our aim was to evaluate the effect of positive C-choline PET/CT results in the therapeutic management of patients with PCa with biochemical relapse (BR) after curative intention treatment. PATIENTS AND METHODS: A total of 112 patients with PCa BR and positive C-choline PET/CT were retrospectively evaluated. PET/CT was acquired 20 min after intravenous administration of 555-740 MBq of C-choline. The therapeutic management after C-choline PET/CT was obtained from the clinical records. The minimum follow-up time was 18 months. RESULTS: In 80 (71.4%) of 112 patients, C-choline PET/CT showed local recurrence of PCa; in 17 (15.2%) patients, distant recurrence; and in 15 (13.4%) patients, local plus distant recurrence. A second malignancy was detected in five (4.5%) patients. The planned therapeutic management was changed as per positive C-choline PET/CT result in 74 (66.1%) patients and were treated as follows: 31 (27.7%) patients with HT, combined with other treatments in eight (7.1%), 17 (15.2%) with BT, 13 (11.6%) with external beam radiotherapy, one (0.9%) with RP, and four (3.6%) with chemotherapy. Treatment approach was not modified in 37 (33%) patients. No data was available from one (0.9%) patient. CONCLUSION: Positive C-choline PET/CT result had an important effect in the therapeutic management of patients with PCa and BR, leading to a change in the planned approach in two (66.1%) out of three patients. In addition, in 4.5% of the patients, the C-choline PET/CT allowed the detection of a second malignancy.

Utility of Amyloid and FDG-PET in Clinical Practice: Differences Between Secondary and Tertiary Care Memory Units.

The clinical utility of amyloid positron emission tomography (PET) has not been fully established. Our aim was to evaluate the effect of amyloid imaging on clinical decision making in a secondary care unit and compare our results with a previous study in a tertiary center following the same methods. We reviewed retrospectively 151 cognitively impaired patients who underwent amyloid (Pittsburgh compound B [PiB]) PET and were evaluated clinically before and after the scan in a secondary care unit. One hundred and fifty concurrently underwent fluorodeoxyglucose (FDG)-PET. We assessed changes between the pre- and post-PET clinical diagnosis and Alzheimer's disease treatment plan. The association between PiB/FDG results and changes in management was evaluated using χ2 and multivariate logistic regression. Concordance between classification based on scan readings and baseline diagnosis was 66% for PiB and 47% for FDG. The primary diagnosis changed after PET in 17.2% of cases. When examined independently, discordant PiB and discordant FDG were both associated with diagnostic change (p < 0.0001). However, when examined together in a multivariate logistic regression, only discordant PiB remained significant (p = 0.0002). Changes in treatment were associated with concordant PiB (p = 0.009) while FDG had no effect on treatment decisions. Based on our regression model, patients with diagnostic dilemmas, a suspected non-amyloid syndrome, and Clinical Dementia Rating <1 were more likely to benefit from amyloid PET due to a higher likelihood of diagnostic change. We found that changes in diagnosis after PET in our secondary center almost doubled those of our previous analysis of a tertiary unit (9% versus 17.2%). Our results offer some clues about the rational use of amyloid PET in a secondary care memory unit stressing its utility in mild cognitive impairment patients.

18F-FDG PET/CT in the follow-up of large-vessel vasculitis: A study of 37 consecutive patients.

OBJECTIVE: 18F-FDG PET/CT has proved to be of potential value for early diagnosis of large-vessel vasculitis (LVV), which frequently involves the aorta. However, its role in the follow-up of these patients has not been well established. Our aim was to evaluate the contribution of 18F-FDG PET/CT in this clinical situation. METHODS: This study included 37 consecutive patients (28 women, 66.5 ± 9.9 years) with an initial 18F-FDG PET/CT positive for LVV and a mean ± standard deviation follow-up PET/CT of 7.5 ± 2.9 months after the initial scan. A semiquantitative analysis of aortic wall uptake was performed calculating the target-to-background ratio (TBR: aortic wall uptake divided by blood pool uptake). The initial and follow-up TBR as well as the clinical and laboratory outcome were compared. RESULTS: Overall, the mean TBR decreased from 1.7 ± 0.5 at the initial scan to 1.5 ± 0.3 at the time of follow-up (p = 0.0001). In the 21 patients who experienced clinical improvement following therapy the TBR also decreased from 1.8 ± 0.6 to 1.5 ± 0.3 (p = 0.0002). However, in the other 16 patients, in whom the treating physician considered that there was no clinical improvement following therapy, no statistically significant differences in TBR were found when data from the first and the follow-up PET/CT scans were compared (1.6 ± 0.3 versus 1.5 ± 0.3, p = 0.1416). Patients who experienced clinical improvement following therapy showed a nonstatistically significant higher TBR at the time of disease diagnosis (1.8 ± 0.6 versus 1.6 ± 0.3; p = 0.12). CONCLUSIONS: The results obtained in the present study highlight the impact of 18F-FDG PET/CT on the management of patients with LVV.

18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging.

Current guidelines do not systematically recommend 18F-FDG PET/CT for breast cancer staging; and the recommendations and level of evidence supporting its use in different groups of patients vary among guidelines. This review summarizes the evidence about the role of 18F-FDG PET/CT in breast cancer staging and the therapeutic and prognostic impact accumulated in the last decade. Other related aspects, such as the association of metabolic information with biology and prognosis are considered and evidence-based recommendations for the use of 18F-FDG PET/CT in breast cancer staging are offered. We systematically searched MEDLINE for articles reporting studies with at least 30 patients related to clinical questions following the Problem/Population, Intervention, Comparison, and Outcome framework. We critically reviewed the selected articles and elaborated evidence tables structuring the summarized information into methodology, results, and limitations. The level of evidence and the grades of recommendation for the use of 18F-FDG PET/CT in different contexts are summarized. Level III evidence supports the use of 18F-FDG PET/CT for initial staging in patients with recently diagnosed breast cancer; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a weak recommendation in this population. In patients with locally advanced breast cancer, level II evidence supports the use of 18F-FDG PET/CT for initial staging; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a strong recommendation in this population. In patients with recently diagnosed breast cancer, the metabolic information from baseline 18F-FDG PET/CT is associated with tumor biology and has prognostic implications, supported by level II evidence. In conclusion, 18F-FDG PET/CT is not recommended for staging all patients with early breast cancer, although evidence of improved regional and systemic staging supports its use in locally advanced breast cancer. Baseline tumor glycolytic activity is associated with tumor biology and prognosis.

Value of the visual and semiquantitative analysis of carbon-11-methionine PET/CT in brain tumors' recurrence versus post-therapeutic changes.

To compare the visual and semiquantitative analysis of carbon-11-methionine (C-MET) PET/computed tomography (CT) images in patients with primary brain tumors and suspected recurrence, persistence, or necrotic post-therapeutic changes. A total of 41 consecutive C-MET-PET/CT scans on 35 (21 men, mean age 44.1±16.6 years) patients were requested for MRI suspicion of recurrent or persistent primary tumor after therapy. The C-MET PET/CT were obtained 20 min after an intravenous injection of 555-740 MBq (15-20 mCi) of C-MET. Both visual and semiquantitative evaluations were performed comparing C-MET uptake between suspicious areas and different lesion/normal-to-background ratios. The final diagnosis was established by histological examination in 12 cases and clinical and MRI follow-up in 29 cases. Visual analyses were positive in 27 (63.4%) and negative in 14 (36.6%) of the C-MET PET/CT. The sensitivity was 83.9%, specificity was 90.0%, positive predictive value was 96.3%, negative predictive value was 64.3% and accuracy was 71.4%. For the semiquantitative analysis, all the lesion/normal-to-background ratios could differentiate between tumor and nontumor (P<0.001), the lesion/contralateral parenchyma (L/CP) maximum standardized uptake value (SUVmax) being the index with the highest area under de curve (0.938). Applying an L/CP SUVmax index of 1.21, the sensitivity was 89.3%, specificity was 90.0%, positive predictive value was 96.1%, negative predictive value was 75%, and accuracy was 82.9%. C-MET-PET/CT was a useful technique to differentiate post-therapeutic changes from tumor presence in treated patients with brain neoplasm in whom cerebral MRI is nonconclusive, showing a high diagnostic performance. Our results showed only slight differences between visual analysis methods and the L/CP SUVmax ratio, the best of the semiquantitative methods.

18F-fluorodeoxyglucose positron emission tomography in the diagnosis of malignancy in patients with paraneoplastic neurological syndrome: a systematic review and meta-analysis.

PURPOSE: The detection of occult cancer in patients suspected of having a paraneoplastic neurological syndrome (PNS) poses a diagnostic challenge. The aim of our study was to perform a systematic review and meta-analysis to assess the diagnostic performance of FDG PET for the detection of occult malignant disease responsible for PNS. METHODS: A systematic review of the literature (MEDLINE, EMBASE, Cochrane, and DARE) was undertaken to identify studies published in any language. The search strategy was structured after addressing clinical questions regarding the validity or usefulness of the test, following the PICO framework. Inclusion criteria were studies involving patients with PNS in whom FDG PET was performed to detect malignancy, and which reported sufficient primary data to allow calculation of diagnostic accuracy parameters. When possible, a meta-analysis was performed to calculate the joint sensitivity, specificity, and detection rate for malignancy (with 95% confidence intervals [CIs]), as well as a subgroup analysis based on patient characteristics (antibodies, syndrome). RESULTS: The comprehensive literature search revealed 700 references. Sixteen studies met the inclusion criteria and were ultimately selected. Most of the studies were retrospective (12/16). For the quality assessment, the QUADAS-2 tool was applied to assess the risk of bias. Across 16 studies (793 patients), the joint sensitivity, specificity, and detection rate for malignancy with FDG PET were 0.87 (95% CI: 0.80-0.93), 0.86 (95% CI: 0.83-0.89), and 14.9% (95% CI: 11.5-18.7), respectively. The area under the curve (AUC) of the summary ROC curve was 0.917. Homogeneity of results was observed for sensitivity but not for specificity. Some of the individual studies showed large 95% CIs as a result of small sample size. CONCLUSIONS: The results of our meta-analysis reveal high diagnostic performance of FDG PET in the detection of malignancy responsible for PNS, not affected by the presence of onconeural antibodies or clinical characteristics.

The Role of PET/CT Molecular Imaging in the Diagnosis of Recurrence and Surveillance of Patients Treated for Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT can metabolically characterize the nature of lesions as benign or malignant, allowing a better staging at the diagnosis of this kind of patient. This advantage can also be applied in the re-staging due to the suspicion of recurrent disease. Many patients have a recurrence of the disease, including surgically treated patients. In the current context, with new personalized oncological treatments, the surveillance for recurrence and its accurate diagnosis are crucial to improve their survival. In this paper, we revise the current knowledge about the clinical and molecular factors related to the recurrent disease. In the context of new, promising, available personalized treatments, the role of molecular imaging with PET/CT and 18F-FDG and non-18F-FDG radiotracers in the follow-up of NSCLC-treated patients is especially attractive and interesting.

Diagnostic role of 11C-Pittsburgh compound B retention patterns and glucose metabolism by fluorine-18-fluorodeoxyglucose PET/CT in amnestic and nonamnestic mild cognitive impairment patients.

OBJECTIVE: Amyloid imaging clinically is usually reported as positive or negative, and the role of amyloid topography has not been studied before. To evaluate in a clinical setting the regional distribution patterns of C-Pittsburgh compound B (C-PIB) and the fluorine-18-fluorodeoxyglucose (F-FDG) uptake in patients with mild cognitive impairment (MCI), we designed this study. METHODS: We studied 81 consecutive MCI patients, 64 amnestic (A-MCI) and 17 nonamnestic (NA-MCI) by C-PIB and F-FDG PET/computed tomography, by visual analysis. PIB retention was classified according to the regional distribution into the following patterns: A (frontal, lateral temporal, basal ganglia and anterior cingulate) and B (global retention). F-FDG images were considered positive only if temporoparietal hypometabolism consistent with Alzheimer's disease was observed. RESULTS: In 42 of the 64 A-MCI, C-PIB was positive. Twelve of the 42 positive A-MCI showed an A-pattern, all F-FDG negative, and 30 a B-pattern, 10 F-FDG positive and 20 F-FDG negative. Of the 17 NA-MCI, C-PIB was positive in three and F-FDG was positive in one. The different proportion of C-PIB positivity in A-MCI and NA-MCI was highly significant (P<0.001). CONCLUSION: Two different C-PIB patterns were observed in MCI patients and for the A-pattern, glucose hypometabolism consistent with Alzheimer's disease is highly unlikely. These findings may contribute towards a better selection of patients for future potential treatments and also to optimize the use of F-FDG-PET/CT.

Amyloid Imaging With 11C-PIB in Patients With Cognitive Impairment in a Clinical Setting: A Visual and Semiquantitative Analysis.

PURPOSE: The aim of this study was to evaluate amyloid imaging with 11C-PIB PET/CT in the study of cognitive impairment in a clinical setting. PATIENTS AND METHODS: The study included 64 patients, with a mean age of 65 years, classified as subjective memory complaints (SMCs; n = 8), nonamnestic mild cognitive impairment (NA-MCI; n = 10), amnestic MCI (A-MCI; n = 19), prodromal Alzheimer disease (AD; n = 12), suspicion of frontotemporal dementia (n = 8), Lewy bodies dementia (DLB; n = 2), and cortical degeneration (CD; n = 5). Ten healthy controls (HCs), with a mean age of 59 years, were also included. 11C-PIB was acquired 60 minutes after IV injection of 555 MBq 11C-PIB. A visual and semiquantitative analysis was performed. RESULTS: In HC, 11C-PIB was negative in 9 and positive in 1. Of the 64 patients, 11C-PIB was negative in 27 (42%) and positive in 37 (58%). 11C-PIB was positive in 3 of 8 SMC, in none of 10 NA-MCI, in 14 of 19 A-MCI, in 10 of 12 prodromal AD, in 3 of 8 frontotemporal dementia, and in the 2 and 5 DLB and CD patients. The semiquantitative results in terms of mean global SUV ratio were 1.13 for HC, 1.36 for SMC, 1.07 for NA-MCI, 2.01 for A-MCI, 2.37 for prodromal AD, 2.75 for DLB, and 2.44 for CD. CONCLUSIONS: In a clinical setting, 11C-PIB scan had a relevant contribution on patients with cognitive impairment, excluding AD in a high proportion of MCI patients and differentiating AD from other dementias. In A-MCI, 11C-PIB revealed ß-amyloid deposit in 74%, whereas it was negative in all NA-MCI patients.

Amyloid imaging with (11)C-PIB PET/CT and glucose metabolism with (18)F-FDG PET/CT in a study on cognitive impairment in the clinical setting.

OBJECTIVE: The objective of this study was to evaluate the contribution of amyloid imaging with (11)C-Pittsburgh compound B ((11)C-PIB) and of glucose metabolism on F-fluorodeoxyglucose ((18)F-FDG) PET/CT to the study of cognitive impairment in the clinical setting. PATIENTS AND METHODS: Thirty-four patients (15 male, 19 female) were enrolled in the study. They were classified according to their clinically presented symptoms. Six patients had subjective memory complaints, five had nonamnestic mild cognitive impairment (MCI), seven had amnestic MCI, seven had prodromal Alzheimer's disease (AD), five had frontotemporal dementia, two had dementia with Lewy bodies, and two had cortical degeneration. All the scans were conducted to determine the likelihood of AD or to differentiate between AD and other dementia. Static 30-min (11)C-PIB and 15-min (18)F-FDG PET/CT scans were obtained. A visual analysis of images was performed. RESULTS: Three of the six patients with subjective memory complaints had positive (11)C-PIB scans and one of them also had (18)F-FDG hypometabolism. All five nonamnestic MCI patients had normal (11)C-PIB and (18)F-FDG. Four of the seven amnestic MCI patients showed (11)C-PIB cortical retention but only one had positive (18)F-FDG. Positive (11)C-PIB and (18)F-FDG were detected in five of the seven prodromal AD patients. All the five patients with FDT had positive (18)F-FDG scans, but only one of the five had (11)C-PIB cortical retention. Both dementia with Lewy bodies and cortical degeneration patients had positive (11)C-PIB and (18)F-FDG scans. CONCLUSION: The combined use of (11)C-PIB and (18)F-FDG PET provides relevant information for the clinical management of cognitive impairment. The detection of positive (11)C-PIB cortical retention in patients may be an indicator of the need for further clinical assessment and monitoring.