PMID- 27219875
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20171218
IS  - 1520-4812 (Electronic)
IS  - 1043-1802 (Linking)
VI  - 27
IP  - 6
DP  - 2016 Jun 15
TI  - Development of (99m)Tc-Labeled Pyridyl Benzofuran Derivatives To Detect 
      Pancreatic Amylin in Islet Amyloid Model Mice.
PG  - 1532-9
LID - 10.1021/acs.bioconjchem.6b00174 [doi]
AB  - While islet amyloid deposition comprising amylin is one of pathological hallmarks 
      of type 2 diabetes mellitus (T2DM), no useful amylin-imaging probe has been 
      reported. In this study, we evaluated two (99m)Tc-labeled pyridyl benzofuran 
      derivatives as novel amylin-imaging probes using the newly established islet 
      amyloid model mouse. Binding experiments in vitro demonstrated that [(99m)Tc]1 
      displayed a higher affinity for amylin aggregates than [(99m)Tc]2. 
      Autoradiographic studies using human pancreas sections with T2DM revealed that 
      [(99m)Tc]1 clearly labeled islet amyloid in T2DM pancreatic sections, while 
      [(99m)Tc]2 did not. Although the initial uptake of [(99m)Tc]1 by the normal mouse 
      pancreas was low (0.74%ID/g at 2 min post-injection), [(99m)Tc]1 showed higher 
      retention in the model mouse pancreas than that of the normal mouse, and 
      exhibited strong binding to amylin aggregates in the living pancreas of the model 
      mice. These results suggest that [(99m)Tc]1 is a potential imaging probe 
      targeting islet amyloids in the T2DM pancreas.
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 - Ono, Masahiro
AU  - Ono 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 - 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 - Kimura, Hiroyuki
AU  - Kimura 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 - Saji, Hideo
AU  - Saji 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160524
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Benzofurans)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Protein Aggregates)
RN  - 0 (Pyridines)
RN  - 7440-26-8 (Technetium)
RN  - LK6946W774 (benzofuran)
RN  - NH9L3PP67S (pyridine)
SB  - IM
MH  - Animals
MH  - Benzofurans/*chemistry/metabolism/pharmacokinetics
MH  - Drug Stability
MH  - Humans
MH  - Islet Amyloid Polypeptide/chemistry/*metabolism
MH  - Isotope Labeling
MH  - Male
MH  - Mice
MH  - Pancreas/*metabolism
MH  - Protein Aggregates
MH  - Pyridines/*chemistry
MH  - Technetium/*chemistry
MH  - Tissue Distribution
EDAT- 2016/05/25 06:00
MHDA- 2017/06/02 06:00
CRDT- 2016/05/25 06:00
PHST- 2016/05/25 06:00 [entrez]
PHST- 2016/05/25 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
AID - 10.1021/acs.bioconjchem.6b00174 [doi]
PST - ppublish
SO  - Bioconjug Chem. 2016 Jun 15;27(6):1532-9. doi: 10.1021/acs.bioconjchem.6b00174. 
      Epub 2016 May 24.