The primary goal of this study was to assess the suitability of 11C-Pittsburgh compound B (11C-PiB) blood–brain barrier delivery (K1) and relative delivery (R1) parameters as surrogate indices of cerebral blood flow (CBF), with a secondary goal of directly examining the extent to which simplified uptake measures of 11C-PiB retention (amyloid-β load) may be influenced by CBF, in a cohort of controls and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). Methods Nineteen participants (6 controls, 5 AD, 8 MCI) underwent MR imaging, 15O-water PET, and 11C-PiB PET in a single session. Fourteen regions of interest (including cerebellar reference region) were defined on MR imaging and applied to dynamic coregistered PET to generate time–activity curves. Multiple analysis approaches provided regional 15O-water and 11C-PiB measures of delivery and 11C-PiB retention that included compartmental modeling distribution volume ratio (DVR), arterial- and reference-based Logan DVR, simplified reference tissue modeling 2 (SRTM2) DVR, and standardized uptake value ratios. Spearman correlation was performed among delivery measures (i.e., 15O-water K1 and 11C-PiB K1, relative K1 normalized to cerebellum [Rel-K1-Water and Rel-K1-PiB], and 11C-PiB SRTM2-R1) and between delivery measures and 11C-PiB retention, using the Bonferroni method for multiple-comparison correction. Results Primary analysis showed positive correlations (ρ ≈0.2–0.5) between 15O-water K1 and 11C-PiB K1 that did not survive Bonferroni adjustment. Significant positive correlations were found between Rel-K1-Water and Rel-K1-PiB and between Rel-K1-Water and 11C-PiB SRTM2-R1 (ρ ≈0.5–0.8, P < 0.0036) across primary cortical regions. Secondary analysis showed few significant correlations between 11C-PiB retention and relative 11C-PiB delivery measures (but not 15O-water delivery measures) in primary cortical areas that arose only after accounting for cerebrospinal fluid dilution. Conclusion 11C-PiB SRTM2-R1 is highly correlated with regional relative CBF, as measured by 15O-water K1 normalized to cerebellum, and cross-sectional 11C-PiB retention did not strongly depend on CBF across primary cortical regions. These results provide further support for potential dual-imaging assessments of regional brain status (i.e., amyloid-β load and relative CBF) through dynamic 11C-PiB imaging.
Purpose: Reliable noninvasive quantitative methods for assessing early response to chemotherapy are vital for development of more personalized cancer therapy management, by allowing earlier decisions regarding therapy changes. The CT RECIST method is widely used; however, CT does not provide information on the physiologic properties of the tumor. In this study, F-18 FDG (FDG) PET is compared to CT in predicting response to chemotherapy using changes in imaging biomarkers of tumor metabolism and size early after initiation of therapy compared to baseline (BL) and follow-up. Materials and Methods: Nine patients with malignant cancer (lung, colorectal, or lymphoma) entered this early therapy response study. All patients received a BL scan before the initiation of chemotherapy, an early therapy assessment (ETA) scan between 2 to 7 weeks after initiation of therapy, and a study end point (FTA) scan between 3 to 9 months. The average length of time between ETA and FTA scans was 4 months. All PET/CT scans were performed on GE ST PET/CT scanner, approximately 60 min after patients received IV injection of approximately 15 mCi of F-18 FDG. All PET/CT images were registered and analyzed on MIMvista workstation to calculate FDG SUV values and CT RECIST measurements. By comparing BL and FTA scans, patients were classified as responders or non-responders based on RECIST. To compare FDG PET and CT data, the largest tumor was identified on CT at BL and its area and SUV were measured at ETA and FTA in each patient. Results: At FTA, responders had an average (FTA CT area)/(BL CT area) of 0.40 and average (FTA SUV)/(BL SUV) of 0.25. For non-responders, these values were 1.55 and 1.27 respectively. At ETA, for responders, (ETA CT area)/(BL CT area) averaged 0.65 and (ETA SUV)/(BL SUV) averaged 0.26. For non-responders, these values were 1.19 and 1.15 respectively. Conclusion: FDG uptake reduction at ETA compared to BL can be used to distinguish responders from non-responders, classified based upon RECIST at FTA. This early change in FDG uptake is more sensitive than early CT changes in predicting response to chemotherapy at FTA. Research Support: This research was supported in part by grant U01 CA140230 from the National Cancer Institute to Dr. Mountz.
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