title: Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.
abstract: The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80% radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [(123)I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Mattner
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Quinlivan
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Greguric
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Jackson
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Berghofer
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: C J R
authors.initials: CJ
authors.lastname: Fookes
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Dikic
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia.
authors.forename: M-C
authors.initials: MC
authors.lastname: Gregoire
authors.affiliation: CEA, DSV/I2BM, Service Hospitalier Frédéric Joliot, 4 Place du Général Leclerc, 91401 Orsay, France.
authors.forename: F
authors.initials: F
authors.lastname: Dolle
authors.affiliation: Life Sciences Division, Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW 2234, Australia ; Department of Molecular Imaging, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Katsifis
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002352:Carrier Proteins / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C525077:2-(6-chloro-2-(4-iodophenyl)-imidazo(1,2-alpha)pyridin-3-yl)-N-ethyl-N-methyl-acetamide; D000081:Acetamides; D002352:Carrier Proteins; D011725:Pyridines; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; C069997:Tspo protein, rat