Synthesis and Evaluation of Novel Chalcone Derivatives with ^99mTc/Re Complexes as Potential Probes for Detection of β-Amyloid Plaques

Abstract

Four 99mTc-labeled chalcone derivatives and their corresponding rhenium analogues were tested as potential probes for imaging β-amyloid plaques. The chalcones showed higher affinity for Aβ(1-42) aggregates than did 99m Tc complexes. In sections of brain tissue from an animal model of AD, the four Re chalcones intensely stained β-amyloid plaques. In biodistribution experiments using normal mice,

Synthesis and evaluation of ethyleneoxylated and allyloxylated chalcone derivatives for imaging of amyloid β plaques by SPECT

“…The tributyltin derivative 5 was prepared from the corresponding iodo derivative 4 using a iodo-totributyltin exchange reaction catalyzed by Pd(0) for a yield of 48%. The starting material 6 for the synthesis of the allyoxylated chalcone derivative 8 was prepared as previously reported 20 .…”

“…We have previously reported Aβ imaging agents based on flavonoid derivatives, such as flavones 15,16 , chalcones [17][18][19][20] , aurones 21,22 , and styrylchromones 23 studies demonstrated that chalcone derivatives fluoro-pegylated at the p-position of the 1-phenyl ring showed a sufficient brain uptake with a good binding capacity to Aβ plaques 19 . In addition, radioiodinated flavonoids, such as flavone and aurone derivatives, with a methoxy or oligoethyleneoxy group at the p-position of the 3-phenyl ring have the properties of high brain uptake and rapid clearance from the brain without significant decrease in the binding affinity for Aβ 15,22 .…”

99mTc/Re complexes based on flavone and aurone as SPECT probes for imaging cerebral β-amyloid plaques

“…Initially, we designed and synthesized four 99m Tc-labeled Ono et al 5/38 chalcone derivatives with monoamine-monoamide dithiol (MAMA) and bis-amino-bis-thiol (BAT) (Figure 1) 29 . MAMA and BAT were selected as a chelation ligand taking into consideration the permeability of the blood-brain barrier, because they form an electrically neutral complex with 99m Tc 30 .…”

“…MAMA and BAT were selected as a chelation ligand taking into consideration the permeability of the blood-brain barrier, because they form an electrically neutral complex with 99m Tc 30 . 99m Tc-BAT-chalcone (n=3) (Figure 1) showed good uptake into and rapid clearance from the brain in addition to high affinity for β-amyloid plaques, indicating it may be a promising probe for the detection of β-amyloid plaques in the brain 29 . Based on the positive results, we decided to further develop new 99m Tc imaging agents based on the flavonoid scaffold.…”

“…We then evaluated the biological potential of these compounds as probes by testing their affinity for A aggregates and -amyloid plaques in sections of brain tissue from Tg2576 mice and their uptake by and clearance from the brain in biodistribution experiments using normal mice. Also, we compared their usefulness as A imaging probes with a 99m Tc-labeled chalcone derivative reported previously 31 . To our knowledge, this is the first time 99m Tc/Re complexes based on flavone and aurone scaffolds have been proposed as probes for the detection of -amyloid plaques in the brain.…”