Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

In Vitro and In Vivo Characterization of Dibenzothiophene Derivatives [125I]Iodo-ASEM and [18F]ASEM as Radiotracers of Homo- and Heteromeric α7 Nicotinic Acetylcholine Receptors

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Structure-Activity Study of an All-d Antimicrobial Octapeptide D2D

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. One-Step Synthesis of N-Succinimidyl-4-[18F]Fluorobenzoate ([18F]SFB)

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Kinetic Modelling of [68Ga]Ga-DOTA-Siglec-9 in Porcine Osteomyelitis and Soft Tissue Infections

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Febrile infections in young children do not frequently induce translocation ETV6-RUNX1

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Glucagon-like peptide-1 receptor regulation of basal dopamine transporter activity is species-dependent

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Imaging HDACs In Vivo: Cross-Validation of the [11C]Martinostat Radioligand in the Pig Brain

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Dynamic coupling of whole-brain neuronal and neurotransmitter systems

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Serotonin release measured in the human brain: a PET study with [11C]CIMBI-36 and d-amphetamine challenge

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

The α7 nicotinic acetylcholine receptor (α7 nAChR) is involved in several cognitive and physiologic processes; its expression levels and patterns change in neurologic and psychiatric diseases, such as schizophrenia and Alzheimer's disease, which makes it a relevant drug target. Development of selective radioligands is important for defining binding properties and occupancy of novel molecules targeting the receptor. We tested the in vitro binding properties of [125I]Iodo-ASEM [(3-(1,4-diazabycyclo[3.2.2]nonan-4-yl)-6-(125I-iododibenzo[b,d]thiopentene 5,5-dioxide)] in the mouse, rat and pig brain using autoradiography. The in vivo binding properties of [18F]ASEM were investigated using positron emission tomography (PET) in the pig brain. [125I]Iodo-ASEM showed specific and displaceable high affinity (~1 nM) binding in mouse, rat, and pig brain. Binding pattern overlapped with [125I]α-bungarotoxin, specific binding was absent in α7 nAChR gene-deficient mice and binding was blocked by a range of α7 nAChR orthosteric modulators in an affinity-dependent order in the pig brain. Interestingly, relative to the wild-type, binding in β2 nAChR gene-deficient mice was lower for [125I]Iodo-ASEM (58% ± 2.7%) than [125I]α-bungarotoxin (23% ± 0.2%), potentially indicating different binding properties to heteromeric α7β2 nAChR. [18F]ASEM PET in the pig showed high brain uptake and reversible tracer kinetics with a similar spatial distribution as previously reported for α7 nAChR. Blocking with SSR-180,711 resulted in a significant decrease in [18F]ASEM binding. Our findings indicate that [125I]Iodo-ASEM allows sensitive and selective imaging of α7 nAChR in vitro, with better signal-to-noise ratio than previous tracers. Preliminary data of [18F]ASEM in the pig brain demonstrated principal suitable kinetic properties for in vivo quantification of α7 nAChR, comparable to previously published data.

OriginalsprogEngelsk
TidsskriftBlood Cells, Molecules, and Diseases
Vol/bind25
Udgave nummer6
ISSN1079-9796
DOI
StatusUdgivet - 20 mar. 2020

ID: 59790001