PMID- 30407835
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20190909
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 15
IP  - 12
DP  - 2018 Dec 3
TI  - Characterization of Novel (18)F-Labeled Phenoxymethylpyridine Derivatives as 
      Amylin Imaging Probes.
PG  - 5574-5584
LID - 10.1021/acs.molpharmaceut.8b00756 [doi]
AB  - Deposition of islet amyloid consisting of amylin constitutes one of pathological 
      hallmarks of type 2 diabetes mellitus (T2DM), and it may be involved in the 
      development and progression of T2DM. However, the details about the relationship 
      between the deposition of islet amyloid and the pathology of T2DM remain unclear, 
      since no useful imaging tracer enabling the visualization of pancreatic amylin is 
      available. In the present study, we synthesized and evaluated six novel 
      (18)F-labeled phenoxymethylpyridine (PMP) derivatives as amylin imaging probes. 
      All (18)F-labeled PMP derivatives showed not only affinity for islet amyloid in 
      the post-mortem T2DM pancreatic sections but also excellent pharmacokinetics in 
      normal mice. Furthermore, ex vivo autoradiographic studies demonstrated that 
      [(18)F]FPMP-5 showed intense labeling of islet amyloids in the diabetes model 
      mouse pancreas in vivo. The preclinical studies suggested that [(18)F]FPMP-5 may 
      have potential as an imaging probe that targets amylin aggregates in the T2DM 
      pancreas.
FAU - Watanabe, Hiroyuki
AU  - Watanabe H
AD  - Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical 
      Sciences , Kyoto University , 46-29 Yoshida Shimoadachi-cho , Sakyo-ku, Kyoto 
      606-8501 , Japan.
FAU - Yoshimura, Masashi
AU  - Yoshimura M
AD  - Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical 
      Sciences , Kyoto University , 46-29 Yoshida Shimoadachi-cho , Sakyo-ku, Kyoto 
      606-8501 , Japan.
FAU - Sano, Kohei
AU  - Sano K
AD  - Division of Clinical Radiology Service , Kyoto University Hospital , 54 Shogoin 
      Kawahara-cho , Sakyo-ku, Kyoto 606-8507 , Japan.
FAU - Shimizu, Yoichi
AU  - Shimizu Y
AD  - Division of Clinical Radiology Service , Kyoto University Hospital , 54 Shogoin 
      Kawahara-cho , Sakyo-ku, Kyoto 606-8507 , Japan.
FAU - Kaide, Sho
AU  - Kaide S
AD  - Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical 
      Sciences , Kyoto University , 46-29 Yoshida Shimoadachi-cho , Sakyo-ku, Kyoto 
      606-8501 , Japan.
FAU - Nakamoto, Yuji
AU  - Nakamoto Y
AD  - Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of 
      Medicine , Kyoto University , 54 Shogoin Kawahara-cho , Sakyo-ku, Kyoto 606-8507 
      , Japan.
FAU - Togashi, Kaori
AU  - Togashi K
AD  - Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of 
      Medicine , Kyoto University , 54 Shogoin Kawahara-cho , Sakyo-ku, Kyoto 606-8507 
      , Japan.
FAU - Ono, Masahiro
AU  - Ono M
AUID- ORCID: 0000-0002-2497-039X
AD  - Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical 
      Sciences , Kyoto University , 46-29 Yoshida Shimoadachi-cho , Sakyo-ku, Kyoto 
      606-8501 , Japan.
FAU - Saji, Hideo
AU  - Saji H
AUID- ORCID: 0000-0002-3077-9321
AD  - Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical 
      Sciences , Kyoto University , 46-29 Yoshida Shimoadachi-cho , Sakyo-ku, Kyoto 
      606-8501 , Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181108
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Molecular Probes)
RN  - 0 (Pyridines)
RN  - 0 (Radiopharmaceuticals)
RN  - GZ5I74KB8G (Fluorine-18)
SB  - IM
MH  - Animals
MH  - Autoradiography/methods
MH  - Diabetes Mellitus, Type 2/*diagnostic imaging/genetics/pathology
MH  - Disease Models, Animal
MH  - Fluorine Radioisotopes/administration & dosage/chemistry/pharmacokinetics
MH  - Humans
MH  - Islet Amyloid Polypeptide/genetics/*metabolism
MH  - Islets of Langerhans/diagnostic imaging/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Probes/administration & dosage/chemistry/*pharmacokinetics
MH  - Pyridines/administration & dosage/chemistry/pharmacokinetics
MH  - Radiopharmaceuticals/administration & dosage/chemistry/*pharmacokinetics
MH  - Tissue Distribution
OTO - NOTNLM
OT  - amylin
OT  - fluorine-18
OT  - imaging
OT  - type 2 diabetes
EDAT- 2018/11/09 06:00
MHDA- 2019/09/10 06:00
CRDT- 2018/11/09 06:00
PHST- 2018/11/09 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/11/09 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.8b00756 [doi]
PST - ppublish
SO  - Mol Pharm. 2018 Dec 3;15(12):5574-5584. doi: 10.1021/acs.molpharmaceut.8b00756. 
      Epub 2018 Nov 8.