Biphenyls labeled with technetium 99m for imaging beta-amyloid plaques in the brain

Nuclear Medicine and Biology
Zhiping ZhuangHank P Kung


Formation and accumulation of excess aggregates of beta-amyloid (Abeta) plaques in the brain are critical factors contributing to the development and progression of Alzheimer's disease (AD). There is an urgent need for in vivo imaging agents that can specifically demonstrate the location and density of Abeta plaques in the brain. The aim of this study was to develop potential technetium 99m (99mTc)-labeled diagnostic imaging agents specific for the detection of Abeta plaques. Based on previously obtained Abeta plaque-specific biphenyls containing a p-N, N-dimethylaminophenyl group, a series of 99mTc and Re-N2S2-biphenyl derivatives was prepared. The stable neutral and lipophilic 99mTc complexes, [99mTc]19 and [99mTc]23, A+B, were successfully obtained. As surrogates for the 99mTc complexes, the corresponding surrogates, Re complexes of 23, were also prepared. Surprisingly, it was found that the Re complexes showed distinctively different retention profiles as compared with the corresponding 99mTc complexes. Biodistribution studies indicated that [99mTc]23A readily passed through the blood-brain barrier (1.18% dose/brain at 2 min) in contrast to the low brain penetration of [99mTc]19 (0.29% dose/brain at 2 min). Initial results ...Continue Reading


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