18F]Fallypride dopamine D2 receptor studies using delayed microPET scans and a modified Logan plot

Abstract

[(18)F]Fallypride PET studies can be used to estimate the nondisplaceable binding potential (BP(ND)) in vivo of dopamine D2/D3 receptor-rich regions of the brain. These studies often take considerable time, up to >or=2 h, limiting the throughput. In this work, we investigated whether limited-duration scans performed subsequent to tracer administration yielded stable BP(ND) estimates. In particular, we applied a modified version of the Logan plot method on the last 60 min of 120-min data and compared the results to those from analysis of the full data set. Fourteen male Sprague-Dawley rats were injected with [(18)F]fallypride intravenously while under isoflurane anesthesia, and dynamic data were acquired on the microPET Focus 220 scanner for 120 min. The distribution volume ratio (DVR=BP(ND)+1) was calculated from a Logan plot using 120 min of data and from a modified version using only the last 60 min. Three of these rats were imaged again on a second day to test the reproducibility. A two-tissue compartment model also was used to fit the time-activity curves (TACs) of the 120-min scans to estimate the parameters K(1), k(2), k(on), k(4) and B(max). These parameters were then used to simulate similar TACs while changing k(on) to reflect changes in the dopaminergic system. The simulated TACs were used as a means for exploring the differences in DVR estimates between the last 60 min only and the full 120 min of simulated data. The average DVR from the full 120-min scans was 13.8+/-0.9, whereas the average DVR estimated from only the last 60 min of data (DVR') was 16.3+/-1.0. The DVR estimates showed good reproducibility in the three rats (mean DVR=13.8+/-1.5 on Day 1 and DVR=13.8+/-0.9 on Day 2). The simulations showed that the relationship between DVR' and DVR estimates follows a semilinear form with varying k(on). Although the BP(ND) estimates are slightly overestimated in a delayed scan mode (i.e., no initial radiotracer uptake measurements) compared to a full scan, this overestimation depends primarily on k(3) (approximately k(on) x B(max)) and has been evaluated in this work for a wide range of k(on) values using simulated TACs. In particular, the sensitivity of DVR' to changes in k(on) is similar to that of DVR. This method of delayed scans eliminates the necessity of imaging during the initial uptake of the radiotracer and, thus, can be used to increase the throughput of studies.