Consideration of Optimal Time Window for Pittsburgh Compound B PET Summed Uptake Measurements

Journal of Nuclear Medicine, The, Mar 2009 by McNamee, Rebecca L, Yee, Seong-Hwan, Price, Julie C, Klunk, William E, Rosario, Bedda, Weissfeld, Lisa, Ziolko, Scott, Berginc, Michael, Lopresti, Brian, DeKosky, Steven, Mathis, Chester A

The standardized uptake value ratio (SUVR, or summed tissue ratio) has been used effectively in Pittsburgh compound B (PiB) PET studies to distinguish subjects who have significant amyloid-β deposition in their brain from those who do not. Relative to quantitative measurements, advantages of the SUVR are improved study feasibility and low test-retest variation; disadvantages include inherent bias (PiB retention overestimation) and potential for time-varying outcomes. The PiB SUVR has proven to be highly correlated with quantitative outcomes and to allow reliable detection of significant group differences (or effective contrasts). In this work, regional PiB SUVRs were examined across 9 time windows to select the window that provided the best trade-offs between bias, correlation, and effective contrast. Methods: A total of 40 dynamic PiB PET studies were performed on controls (n = 16), patients with Alzheimer disease (AD; n = 11), and patients with mild cognitive impairment (MCI; n = 13) (555 MBq [15 mCi], 90-min scan, and arterial blood sampling). The SUVR was computed for five 20-min and four 30-min windows that spanned the 30- to 90-min postinjection period. The SUVRs were compared with Logan graphical distribution volume ratio (DVR) measurements (35-90 min), determined with arterial blood as input and without arterial blood as input (cerebellum as reference). Results: Greater correlation and more bias were generally observed for the SUVR measurement at later times than at earlier times (relative to DVR). The effective contrast between the control and AD PiB SUVRs was slightly better for earlier data than for later data. The temporal dynamics of the SUVR measurement indicated greater stability in the measurement at 40 min after injection. Conclusion: The 50- to 70-min time window provided a good compromise between physiologic validity, stability, sensitivity, and clinical feasibility across the control, MCI, and AD subject data examined in this study. The 40- to 60-min period demonstrated many advantages and should be used in studies limited by low injected dose. Although more biased than the 40- to 60-min SUVR, the 50- to 70-min SUVR was thought to be optimal because of greater measurement stability, which may prove to be important for longitudinal multisite studies performed in control, MCI, and AD subjects that are not dose-limited.

Key Words: Pittsburgh compound B; PiB; SUV; SUVR; distribution volume ratio; DVR; PET

J Nucl Med 2009; 50:348-355

DOI: 10.2967/jnumed.108.057612

Pittsburgh compound B (PiB) is a uC-labeled thioflavin-T derivative that has become widely used (1-3) in imaging amyloid-β-protein deposits with PET. Amyloid imaging has proven to be useful in the study of Alzheimer disease (AD) (4-11).

In the proof-of-concept human studies (4), PiB retention was assessed using the semiquantitative standardized uptake value ratio (SUVR; summed tissue uptake over 40-60 min), and these results were subsequently verified by fully quantitative studies performed in controls, patients with mild cognitive impairment (MCI), and patients with AD (5,6). These early studies consistently showed that PiB uptake in AD patients was nearly twice that in controls in specific cortical areas (P

Quantitative studies require dynamic sampling of the radiotracer kinetics in brain and blood at many times throughout the study (e.g., 30-40 points over ≥90 min), analysis of arterial plasma to determine the metabolitecorrected arterial input function, and compartmental modeling analyses to obtain regional binding measurements (e.g., distribution volume ratio [DVR] = total distribution volume [V^sub T^]/nondisplaceable distribution volume [V^sub ND^]). The quantitative arterial input-based DVR measurements generally serve as gold-standard outcomes for subsequent evaluations directed toward the identification of valid simpler methods that do not require blood sampling and allow for shorter data-collection times.

Lopresti et al. (6) analyzed simplified PiB PET data over 60- and 90-min intervals using the linear Logan graphical analysis with different input functions that were either arterial, image-derived carotid, or image-derived cerebellar data. Data also were analyzed with a simplified reference tissue method and the summed SUVR. Although results obtained using data over the full 90-min scan interval were less variable than were data over the shorter 60-min interval, the 60-min data provided useful results. Of all compared methods, the SUVR approach was the most robust in terms of test-retest variability and maximum effect size between AD patients and controls, although the SUVR method required the shortest scan time (e.g., 40-60 min or 40-90 min). The SUVR is easy to compute, requires no arterial input function, and produces data with a large dynamic range, thereby making it a potential candidate for routine clinical studies (6). SUVR can also serve as an approximation of DVR, although bias (overestimation relative to the true DVR) can arise as a result of plasma clearance (12).