Objective:

Alzheimer’s disease (AD), which comes up an important problem due to the aging population, has two hallmarks defined as amyloid plaques and neurofibrillary tangles. Despite the fact that AD affects a wide audience adversely, definitive diagnosis of AD still requires postmortem examination of the brain through histological staining of these hallmarks. Nowadays, these two hallmarks are playing crucial role in researches for diagnosis and treatment of AD. In addition, deficiency of AD diagnosis agents and limitation of assessing the blood-brain barrier (BBB) are main reasons of the current researches focusing on brain agents with plaque or tangle imaging potential. Metal-protein attenuating compounds (MPACs) such as clioquinol and cloxyquin have a great increasing promise on amyloid plaques. Yurt Kilcar et al. radiolabeled Bioquin-Hexa methyl propylene amine oxime (HMPAO) with 99mTc (99mTc-Bioquin-HMPAO) and evaluated the biodistribution on healthy male Balb/C mice (unpublished data). In current study, it is aimed to investigate amyloid plaque specifity of the 99mTc-Bioquin-HMPAO by using biodistribution studies on animal model of AD.

Methods:

Bioquin-HMPAO was labeled with 99mTc according to previous study. In accordance with the objectives of the study, animal model of AD created on healthy male Sprague Dawley rats with intrahippocampal stereotaxic injection of amyloid beta 1-42 (Aβ1-42). Intrahippocampal administration was applied to the CA1 area of hippocampus bilaterally (Aβ1-42 to the left side and PBS to the right side as control). Additionally, healthy male Sprague Dawley rats were utilized as naïve group. Twenty days after surgery, biodistribution studies of 99mTc-Bioquin-HMPAO on animal model of AD and control group were performed. Furthermore, saturation with Bioquin-7-carboxylic acid (Aβ targeting side of Bioquin-HMPAO) was applied for both experimental groups. Nissl staining for animal model of AD was performed. All animal experiments were carried out under the approval of the relevant Institutional Animal Review Committee of Ege University, (Number: 2010-155) İzmir, Turkey.

Results:

Higher uptakes on hippocampus were observed at Aβ1-42 injected side in animal model of AD when compared with the control and naïve groups. Saturated studies with Bioquin-7-carboxylic acid compound showed that 99mTc labeled Bioquin-HMPAO compound has specificity on amyloid plaques (Figure 1).

Conclusion:

Consequences of the whole experimental studies, it is proposed that the radiolabeled compound (99mTc-Bioquin-HMPAO) might be improved and used as a novel brain amyloid plaque specific agent promising early diagnosis potential of AD.

Keywords: Alzheimer’s disease,brain imaging,HMPAO,bioquin,Tc-99m,animal model