Exploratory human PET study of the effectiveness of (11)C-ketoprofen methyl ester, a potential biomarker of neuroinflammatory processes in Alzheimer's disease

Autor: Tomohiko Yamane, Hisashi Doi, Hiroyuki Nishida, Hirotaka Onoe, Shogo Kimoto, Miho Shukuri, Tomoko Mikami, Tomoyuki Nishio, Yasuji Yamamoto, Aya Mawatari, Hiroko Shinkawa, Akihito Ohnishi, Yasuyoshi Watanabe, Kazuki Aita, Yasuhiko Ikari, Masahiro Sasaki, Michio Senda, Go Akamatsu
Rok vydání: 2016
Předmět:
Zdroj: Nuclear medicine and biology. 43(7)
ISSN: 1872-9614
Popis: Introduction Neuroinflammatory processes play an important role in the pathogenesis of Alzheimer's disease (AD). As a biomarker of neuroinflammatory processes, we designed 11 C-labeled ketoprofen methyl ester ([ 11 C]KTP-Me) to increase the blood–brain barrier permeability of ketoprofen (KTP), a selective cyclooxygenase-1 (COX-1) inhibitor. Animal studies indicated that [ 11 C]KTP-Me enters the brain and accumulates in activated microglia of inflammatory lesions. In a first-in-human study, we reported that [ 11 C]KTP-Me is a safe positron emission tomography (PET) tracer and enters the brain; the radioactivity is washed out from normal cerebral tissue. Here we explored the efficacy of [ 11 C]KTP-Me as a diagnostic biomarker of neuroinflammatory processes in AD. Methods [ 11 C]KTP-Me was synthesized by rapid C -[ 11 C]methylation of [ 11 C]CH 3 I and the corresponding arylacetate precursor. Nine subjects (four healthy subjects, two Pittsburgh compound-B (PiB)-positive patients with mild cognitive impairment (MCI), and three PiB-positive AD patients) underwent a dynamic brain PET scan for 70min after injection. We evaluated differences in cortical retention and washout rate in the brain between healthy subjects and MCI/AD patients. Results A brain distribution pattern reflecting blood flow in the early-phase image was seen in both healthy subjects and MCI/AD patients. Cortical activity gradually cleared in all groups. However, we observed no obvious difference in the washout rate between healthy subjects and MCI/AD patients or between MCI and AD patients. Conclusions [ 11 C]KTP-Me cannot be useful as a potential diagnostic biomarker for MCI/AD. Further improvements in binding affinity and specificity, etc., are needed to be a diagnostic biomarker of neuroinflammation in AD. Advances in knowledge and implications for patient care [ 11 C]KTP-Me is a new tracer that targets COX-1. [ 11 C]KTP-Me is expected to be a diagnostic biomarker of neuroinflammation in AD in the future. The effectiveness was limited in a small number of AD patients. Therefore, further studies are needed to clarify the usefulness of [ 11 C]KTP-Me.
Databáze: OpenAIRE
Externí odkaz: