RT Journal Article
SR Electronic
T1 Scatchard analysis of 5-HT<sub>1B</sub> receptors with [<sup>11</sup>C]P943 in non-human primates
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 79P
OP 79P
VO 49
IS supplement 1
A1 Richard Carson
A1 Nabeel Nabulsi
A1 David Weinzimmer
A1 Christine Sandiego
A1 Jean-Dominique Gallezot
A1 Ellen Wang
A1 Stafford McLean
A1 Yiyun Huang
A1 Yu-Shin Ding
YR 2008
UL http://jnm.snmjournals.org/content/49/supplement_1/79P.3.abstract
AB 312 Objectives: [11C]P943 is a selective 5-HT1B receptor antagonist suitable for quantitative PET studies. The purpose of this study was to measure Bmax and Kd in non-human primates and to evaluate the assumptions of uniform Kd and non-displaceable uptake (NDU) throughout the brain. Methods: Studies were performed in 3 isoflurane-anesthetized rhesus monkeys with 3 bolus+infusion deliveries of [11C]P943 per day on 1-2 days. Specific activity (SA) was varied from 2-200 MBq/nmol. Dynamic scans were acquired on the HRRT and 8 ROIs were defined on MR images co-registered to summed PET images. Binding potentials (BPND), determined by the equilibrium ratios of ROIs to cerebellum (CER), were used to estimate Bmax and Kdapp (Kd/fND) by non-linear fitting. Two analyses were performed: 1) assuming NDU was equal to CER activity, and 2) estimating NDU by a scale factor (S) times CER activity. Results: Equilibrium was reached by ~70 min and data from 70-100 min were used to calculate BP. Analysis 1: Highest BPND values were 0.80 and 0.57 in occipital cortex and globus pallidus, respectively. Mean Kdapp and Bmax were 27 nM and 12 nM, respectively, with estimation uncertainties (%SE) of ~50%. The regional variation of Kdapp was 40%, consistent with the %SE. Kdapp was consistent with the in vitro Kd value (0.46 nM) after correction for fND (~0.01), calculated from plasma free fraction (0.25) and VND (28). Analysis 2: A statistically improved fit occurred for 3/8 ROIs. However, %SE increased dramatically and S was overly sensitive to the lowest SA data. Conclusions: Quantitative estimates of Bmax and Kdapp for [11C]P943 can be obtained with PET. However, validation of the assumptions of uniform Kd and NDU would require a larger dataset. Research Support: Yale-Pfizer Bioimaging Alliance