Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-β.
Non-invasive imaging of amyloid-β in the brain, a hallmark of Alzheimer's disease, may support earlier and more accurate diagnosis of the disease. In this study, we assessed the novel single photon emission computed tomography tracer (123)I-ABC577 as a potential imaging biomarker for amyloid-β in the brain. The radio-iodinated imidazopyridine derivative (123)I-ABC577 was designed as a candidate for a novel amyloid-β imaging agent. The binding affinity of (123)I-ABC577 for amyloid-β was evaluated by saturation binding assay and in vitro autoradiography using post-mortem Alzheimer's disease brain tissue. Biodistribution experiments using normal rats were performed to evaluate the biokinetics of (123)I-ABC577. Furthermore, to validate (123)I-ABC577 as a biomarker for Alzheimer's disease, we performed a clinical study to compare the brain uptake of (123)I-ABC577 in three patients with Alzheimer's disease and three healthy control subjects. (123)I-ABC577 binding was quantified by use of the standardized uptake value ratio, which was calculated for the cortex using the cerebellum as a reference region. Standardized uptake value ratio images were visually scored as positive or negative. As a result, (123)I-ABC577 showed high binding affinity for amyloid-β and desirable pharmacokinetics in the preclinical studies. In the clinical study, (123)I-ABC577 was an effective marker for discriminating patients with Alzheimer's disease from healthy control subjects based on visual images or the ratio of cortical-to-cerebellar binding. In patients with Alzheimer's disease, (123)I-ABC577 demonstrated clear retention in cortical regions known to accumulate amyloid, such as the frontal cortex, temporal cortex, and posterior cingulate. In contrast, less, more diffuse, and non-specific uptake without localization to these key regions was observed in healthy controls. At 150 min after injection, the cortical standardized uptake value ratio increased by ∼ 60% in patients with Alzheimer's disease relative to healthy control subjects. Both healthy control subjects and patients with Alzheimer's disease showed minimal (123)I-ABC577 retention in the white matter. These observations indicate that (123)I-ABC577 may be a useful single photon emission computed tomography imaging maker to identify amyloid-β in the human brain. The availability of an amyloid-β tracer for single photon emission computed tomography might increase the accessibility of diagnostic imaging for Alzheimer's disease.
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan yoshifumi_maya@nmp.co.jp.
Yoshifumi
Y
Maya
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Yuki
Y
Okumura
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Ryohei
R
Kobayashi
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Takako
T
Onishi
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Yoshinari
Y
Shoyama
2 Molecular Neuroimaging, New Haven, CT, USA.
Olivier
O
Barret
2 Molecular Neuroimaging, New Haven, CT, USA.
David
D
Alagille
2 Molecular Neuroimaging, New Haven, CT, USA.
Danna
D
Jennings
2 Molecular Neuroimaging, New Haven, CT, USA.
Kenneth
K
Marek
2 Molecular Neuroimaging, New Haven, CT, USA.
John
J
Seibyl
2 Molecular Neuroimaging, New Haven, CT, USA.
Gilles
G
Tamagnan
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Akihiro
A
Tanaka
1 Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Yoshifumi
Y
Shirakami
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055815:Young Adult
C000607819:123I-ABC577; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D007093:Imidazoles; D011725:Pyridines
Alzheimer’s disease; amyloid-β; imaging; radiotracer; single photon emission computed tomography