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Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography

The cerebral distribution of peripheral‐type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 binding sites in healthy brain. Therefore, we used quantitative autoradiography to measure the saturation binding parameters for [3H]PK11195 in cryostat sections from young Landrace pigs. Specific binding was lowest in the cerebellar white matter (85 fmol mg−1) and highest in the caudate nucleus (370 fmol mg−1), superior colliculus (400 fmol mg−1), and anterior thalamic nucleus (588 fmol mg−1). The apparent affinity was in the range of 2–6 nM in vitro, predicting high specific binding in PET studies of living brain. However, the distribution volume (Vd, ml g−1) of high specific activity [11C]PK11195 was nearly homogeneous (3 ml g−1) throughout brain of healthy Landrace pigs, and was nearly identical in studies with lower specific activity, suggesting that factors in vivo disfavor the detection of PBBS in Landrace pigs with this radioligand. In young, adult Göttingen minipig brain, the magnitude of Vd for [11C]PK11195 was in the range 5–10 ml g−1, and had a heterogeneous distribution resembling the in vitro findings in Landrace pigs. There was a trend toward globally increased Vd in a group of minipigs with acute MPTP‐induced parkinsonism, but no increase in Vd was evident in the same pigs rescanned at 2 weeks after grafting of fetal mesencephalon to the partially denervated striatum. Thus, [11C]PK11195 binding was not highly sensitive to constituitively expressed PBBS in brain of young Landrace pigs, and did not clearly demonstrate the expected microglial activation in the MPTP/xenograft model of minipigs. Synapse 59:418–426, 2006. © 2006 Wiley‐Liss, Inc.