Iodinated PK 11195 as an ex vivo marker of neuronal injury in the lesioned rat brain

Abstract

In order to study the potentials of indirect and direct detection of neuronal damages in humans by single photon emission computerized tomography (SPECT), we compared ex vivo cerebral biodistribution of [125I]PK 11195 with that of [125I]TISCH in a rat model of unilateral striatal excitotoxic lesion. Experiments on in vitro binding with [3H]PK 11195 as a ligand for peripheral type benzodiazepine binding sites (PTBBS) and [3H]SCH 23390 as a ligand for dopamine D1 receptors were also performed to validate our experimental model. We observed a very high increase in the PTBBS and a dramatic decrease in the D1 receptors on the lesioned striatum compared to the intact side. Moreover, we showed that [125I]PK 11195 bound specifically to PTBBS in lesioned cerebral areas ex vivo 5 days after striatal infusion of quinolinic acid (600 nmoles). Increases of 192%, 168%, and 30% were obtained in the striatum, the cortex, and the hippocampus, respectively, on the lesioned side. These results showed that iodinated PK 11195 bound specifically to PTBBS ex vivo and that this binding was dramatically increased at the sites of brain lesion. This ligand could therefore be suitable to detect brain injuries in humans by SPECT, complementing the information given by ligands which image loss in a specific neuron population.

TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT

“…In contrast, 124 I-PK 11195's longer half-life (4.2 days) enables us to image tumors. Although there are some publications that report using ligands of TSPO to image brain, for example, Chalon et al 30 reported use of iodinated PK 11195 as an ex vivo marker of neuronal injury in the lesioned rat brain, we are the first to use 124 I-PK 11195 as the imaging agent for cancers here. In our approach to develop a bifunctional agent for both tumor imaging and phototherapy, we are interested in conjugating I-PK 11195 with photosensitizers.…”

Synaptic localization of GABAA receptor subunits in the substantia nigra of the rat: effects of quinolinic acid lesions of the striatum

“…Injections of the excitotoxin, quinolinic acid (QA; Sigma‐Aldrich, Poole, UK), were stereotaxically placed in the dorsal region of the right striatum at two loci (coordinates: 8.0 mm anterior to bregma; 2.4 mm lateral to the midline; and 3.5 and 5.0 mm ventral to the pial surface) using a Hamilton syringe. Each rat received a total of 120 nmol of QA in 1 µL of phosphate‐buffered saline (PBS; 0.01 m phosphate, pH 7.4) over a 10‐min period (Chalon et al ., 1996; Nakao et al ., 1996; Nicholson et al ., 1996). The cannula was then left in position for a further 5 min before being slowly removed.…”

Synthesis of [123I]iodine labelled imidazo[1,2-b] pyridazines as potential probes for the study of peripheral benzodiazepine receptors using SPECT

“…Radiolabelled analogues of these compounds, particularly 11 C and 123 I labelled PK 11 195 have subsequently been used to map PBR receptors in the human heart and brain as well as imaging tumours and neurological disorders in vivo [22][23][24][25][26].…”