Subject(s)
Luminescence , Prostatic Neoplasms , Edetic Acid/analogs & derivatives , Gallium Isotopes , Gallium Radioisotopes , Humans , Male , Oligopeptides , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , RadiopharmaceuticalsABSTRACT
OBJECTIVE: To examine the influence of the APOE genotype on levels of beta-amyloid (Abeta) plaque load and atrophy in patients with Alzheimer disease (AD) in vivo. METHODS: Thirty-two patients with moderate AD were divided into carriers and noncarriers of the epsilon4 allele. These groups were matched for age, disease duration, education, and cognitive impairment. In all subjects, [11C]PIB-PET was performed for measurement of cerebral Abeta plaque deposition and cranial MRI for the assessment of gray matter volume by voxel-based morphometry (VBM) and for correction of partial volume effects (PVE) in the PET data. Voxel-based comparisons (SPM5) were performed between patient groups and healthy control populations and completed with multiple regression analyses between imaging data and epsilon4 allele frequency. RESULTS: Compared to controls, AD-typical patterns of [11C]PIB retention and atrophy were detected in both epsilon4-positive and epsilon4-negative patient groups. In direct comparison, significantly stronger and more extended [11C]PIB uptake was found in epsilon4-positive patients in bilateral temporoparietal and frontal cortex, surviving PVE correction. VBM analysis demonstrated comparable levels of atrophy in both patient groups. Regression analyses revealed a linear association between higher epsilon4 allele frequency and stronger temporoparietal Abeta plaque deposition, independently of other confounds. No major correlation between epsilon4 allele frequency and gray matter decrease was observed. CONCLUSION: These results indicate that the epsilon4-positive APOE genotype not only represents a risk factor for Alzheimer disease (AD), but also results in higher levels of Abeta plaque deposition in epsilon4-positive patients with AD compared to age-matched epsilon4-negative patients with similar levels of cognitive impairment and brain atrophy. The potential role of Abeta plaque imaging for patient inclusion and follow-up in anti-amyloid therapy trials is strengthened by these findings.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/pathology , Apolipoproteins E/genetics , Brain/pathology , Plaque, Amyloid/pathology , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Amyloid beta-Peptides/metabolism , Aniline Compounds , Apolipoprotein E4/genetics , Benzothiazoles , Brain/diagnostic imaging , Brain/metabolism , Carbon Radioisotopes , DNA Mutational Analysis , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genetic Testing , Genotype , Humans , Male , Middle Aged , Plaque, Amyloid/metabolism , Positron-Emission Tomography , Risk Factors , ThiazolesABSTRACT
PURPOSE: An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [(11)C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. METHODS: Sixty-three patients (mean age, 68.8 +/- 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 +/- 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [(11)C]Choline PET/CT. Patients underwent a [(11)C]Choline-PET/CT study after injection of 656 +/- 119 MBq [(11)C]Choline on a Sensation 16 Biograph PET/CT scanner. RESULTS: Of the 63 patients, 35 (56%) showed a pathological [(11)C]Choline uptake. The detection rate of [(11)C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value <1 ng/ml, 43% for a PSA-value 1-<2 ng/ml, 62% for a PSA-value 2-<3 ng/ml and 73% for a PSA-value >or=3 ng/ml. Anti-androgen therapy did not show a significant effect on the detection rate of [(11)C]Choline-PET/CT (p = 0.374). CONCLUSION: As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [(11)C]Choline-PET/CT is 36%. Furthermore, the detection rate of [(11)C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [(11)C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).
