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,

Two 99m Tc/Re complexes based on flavone and aurone were tested as potential probes for imaging -amyloid plaques using single photon emission computed tomography. Both 99m Tc-labeled derivatives showed higher affinity for A aggregates than did 99m Tc-BAT. In sections of brain tissue from an animal model of AD, the Re-flavone derivative 9 and Re-aurone derivative 19 intensely stained -amyloid plaques. In biodistribution experiments using normal mice, 99m Tc-labeled flavone and aurone displayed similar radioactivity pharmacokinetics. With additional modifications to improve their brain uptake, 99m Tc complexes based on the flavone or aurone scaffold may serve as probes for imaging cerebral -amyloid plaques Key words: Alzheimer's disease, -amyloid plaque, Tc-99m, single photon emission computed tomography (SPECT), imaging. Ono et al. 3/38Alzheimer's disease (AD) is a neurodegenerative disorder of the brain associated with irreversible cognititive decline, memory impairment, and behavioral changes.Currently, the only definitive confirmation of AD is by postmortem histopathological examination of -amyloid plaques in the brain. The early appraisal of clinical symptoms for a diagnosis of AD is often difficult and unreliable. Numerous reports suggest the accelerated accumulation of -amyloid plaques in the brain to be a key risk factor associated with AD. Consequently, the detection of individual -amyloid plaques in vivo by single photon emission tomography (SPECT) or positron emission tomography (PET) should improve the diagnosis of and also accelerate the discovery of effective therapeutic agents for AD [1][2][3][4] There are more SPECT scanners than PET imaging devices installed for routine clinical imaging, which provides a certain advantage to using SPECT imaging agents. Since SPECT is more valuable than PET in terms of routine diagnostic use, the development of more useful Aβ imaging agents for SPECT has been a critical issue. Although many radioiodinated SPECT imaging agents for detecting β-amyloid plaques have been reported, there are few reports on the development of 99m Tc imaging agents. Ono et al. 4/38 99m Tc (T 1/2 = 6.01 h, 141 keV) has become the most commonly used radionuclide in diagnostic nuclear medicine for several reasons: it is readily produced by an 99 Mo/ 99m Tc generator, the gamma-ray energy it emits is suitable for detection, and its physical half-life is compatible with the biological localization and residence time required for imaging. Its ready availability, essentially 24 h a day, and easiness of use make it the radionuclide of choice. New 99m Tc-labeled imaging agents will provide simple, convenient, and widespread SPECT-based imaging methods for detecting and eventually quantifying-amyloid plaques in living brain tissue.It has been reported that a dopamine transporter imaging agent, [ 99m Tc]TRODAT-1, is useful to detect the loss of dopamine neurons in the basal ganglia associated with Parkinson's disease. This is the first example of a 99m Tc imaging agent t...

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