[(18)F]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.

Methods: 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.

Results: 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).

Conclusion: 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.

Figure 1

A two-tissue plus plasma compartment model. The cerebellum, which contain little or no dopamine D2/3 receptors, is governed by Cp and CF+NS, while the striatum, which is a D2/3 receptor-rich region, is governed by all 3 compartments.

Figure 2

PET image registered to CT (left) of a rat injected with [18F]fallypride. The striata are D2 rich regions while the cerebellum is D2 poor. The same CT image was registered to an MRI rat brain template (right). Regions of interest (ROIs) were drawn over the striata and cerebellum in the template and transformed to the PET image.

Figure 3

Distribution volume ratio (DVR) estimates at different time points of a rat injected with [¹⁸F]fallypride and imaged in the microPET for 150 min.

Figure 4

Time activity curves (TACs) of cerebellum and striatal uptake of [¹⁸F]Fallypride in a 120 min dynamic PET acquisition. The striatum TAC was fitted using a two-tissue compartment model and a realistic plasma input function.

Figure 5

Logan plots of a rat injected with [18F]Fallypride and imaged in the mPET for 120 min while anesthetized with 1.5% isoflurane. The Logan plot of the full 120 min data (DVR = 13.9 ± 0.2) is compared here to the Logan plot of the last 60 min (DVR′ = 16.6 ± 0.8) of the 120 min data after neglecting the the first 60 min.

Figure 6

Statistical display of the DVR estimates from a 120 min scan versus the DVR′ estimates of the last 60 min of data from the full 120 min after neglecting the first 60 min.

Figure 7

Correlation of DVR and DVR′ obtained from fitting the 120 min and the last 60 min of simulated TACs as a function of kon, respectively, while varying kon. (a) The simulated TACs used the parameters obtained from fitting the experimental TACs to a two-tissue compartment model. (b) The simulated TACs used the NHP kinetic uptake parameters found in the literature [3].