PMID- 32202808
OWN - NLM
STAT- MEDLINE
DCOM- 20210528
LR  - 20210528
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 17
IP  - 4
DP  - 2020 Apr 6
TI  - Development of Novel PET Imaging Probes for Detection of Amylin Aggregates in the 
      Pancreas.
PG  - 1293-1299
LID - 10.1021/acs.molpharmaceut.9b01309 [doi]
AB  - The deposition of islet amyloid is associated with beta-cell mass dysfunction in 
      type 2 diabetes mellitus (T2DM). Since the amylin aggregate is the main component 
      of islet amyloid, in vivo imaging of amylin may be useful for diagnosis and 
      elucidation of the pathogenic mechanism of T2DM. In the present study, we newly 
      designed, synthesized, and evaluated two (18)F labeled compounds ([(18)F]DANIR-F 
      2b and [(18)F]DANIR-F 2c) as positron emission tomography (PET) probes targeting 
      amylin aggregates. In an in vitro binding study, DANIR-F 2b and DANIR-F 2c showed 
      binding affinity for amylin aggregates (K(i) = 160 and 29 nM, respectively). In 
      addition, [(18)F]DANIR-F 2b and [(18)F]DANIR-F 2c clearly labeled islet amyloids 
      in in vitro autoradiography of T2DM pancreatic sections. In the biodistribution 
      study using normal mice, [(18)F]DANIR-F 2b and [(18)F]DANIR-F 2c displayed 
      favorable pharamacokinetics in the pancreas and some organs located near the 
      pancreas. Furthermore, in an ex vivo autoradiographic study, [(18)F]DANIR-F 2c 
      also bound to amylin aggregates in the pancreas of the amylin transplanted mice. 
      The results of this study suggest that [(18)F]DANIR-F 2c shows fundamental 
      properties as a PET imaging probe targeting amylin aggregates in the T2DM 
      pancreas.
FAU - Watanabe, Hiroyuki
AU  - Watanabe H
AUID- ORCID: 0000-0002-8873-1224
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 - Kawano, Kiyoshiro
AU  - Kawano K
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 - Shimizu, Yoichi
AU  - Shimizu 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 - Iikuni, Shimpei
AU  - Iikuni 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200323
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Fluorine Radioisotopes)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - GZ5I74KB8G (Fluorine-18)
SB  - IM
MH  - Animals
MH  - Autoradiography/methods
MH  - Diabetes Mellitus, Type 2
MH  - Fluorine Radioisotopes/metabolism
MH  - Humans
MH  - Islet Amyloid Polypeptide/*metabolism
MH  - Islets of Langerhans/metabolism
MH  - Male
MH  - Mice
MH  - Pancreas/*metabolism
MH  - Positron-Emission Tomography/methods
MH  - Tissue Distribution/physiology
OTO - NOTNLM
OT  - PET
OT  - amylin
OT  - fluorine-18
OT  - islet amyloid
OT  - type 2 diabetes mellitus
EDAT- 2020/03/24 06:00
MHDA- 2021/05/29 06:00
CRDT- 2020/03/24 06:00
PHST- 2020/03/24 06:00 [pubmed]
PHST- 2021/05/29 06:00 [medline]
PHST- 2020/03/24 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.9b01309 [doi]
PST - ppublish
SO  - Mol Pharm. 2020 Apr 6;17(4):1293-1299. doi: 10.1021/acs.molpharmaceut.9b01309. 
      Epub 2020 Mar 23.