The distribution of radioactivity in brains of rats given [N-methyl-11C]PK 11195 in vivo after induction of a cortical ischaemic lesion

PK 11195 is a selective ligand for the peripheral-type benzodiazepine binding site (PTBBS). There are few such sites in normal brain but their number increases in association with tissue necrosis. The time-course of appearance of PTBBS around a focally induced ischaemic lesion in frontal cortex of rat brain was established by autoradiography using [N-methyl-³H]PK 11195. Using this information and the same experimental model of ischaemia, the distribution of radioactivity after injection of carbon-11 ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{= 20.3}\text{min}$, β⁺ = 99.8%) labelled PK 11195 was studied. The purpose was to synthesize [N-methyl-¹¹C]PK 11195 and to test its suitability as a tracer for depicting the presence of PTBBS in ischaemic lesions. The time-profiles of distribution of radioactivity in brain regions after intravenous injection of tracer and the ratio of radioactivity in lesioned compared with unlesioned cortex were determined. Data for the temporal (days after lesion induction) and for the regional retention of radioactivity were consistent with independent evidence (autoradiographic and immunohistochemical) for the occurrence of increased numbers of PTBBS, predominantly in association with macrophages, in areas undergoing necrosis.