淀粉样蛋白PET影像检查可追踪痴呆进展

在迈阿密召开的核医学与分子影像学会(SNMMI)年会上，澳大利亚墨尔本市奥斯汀医院的Christopher Rowe医生及其同事报告了关于研究性药物11C-匹兹堡复合物B(PiB)和18F-florbetaben的两项研究的结果：对于轻度认知功能障碍(MCI)患者，使用PET影像放射性示踪剂对b淀粉样蛋白沉积进行2~3年的纵向追踪，有助于预测进展为阿尔茨海默病或可靠地排除这一诊断。

PiB研究的全称为澳大利亚老年影像、生物标志物和生活方式旗舰研究，共纳入92例MCI患者。结果显示，基线时在65%的MCI患者中检出高PiB结合。3年后，基线时高b淀粉样蛋白负荷扫描阳性患者中有66%被诊断为阿尔茨海默病，而扫描阴性的MCI患者中仅有7%被诊断为阿尔茨海默病。6年随访结果显示，患者的b淀粉样蛋白积聚速度“令人难以置信的缓慢”，大约为每年2%。“如果扫描结果显示为阴性，则可以确信，在此后至少10年内都不会患阿尔茨海默病。”但PiB的半衰期仅为20 min，不适于临床应用；而Florbetaben和其他18F淀粉样蛋白放射性示踪剂的半衰期为2 h，在临床应用中效价比要高得多。

Florbetaben研究中共纳入45例MCI患者，这些患者接受此种化合物的PET影像研究。结果显示，基线时53%的患者有高水平的新皮质结合。2年后，已有高水平结合患者的结合率增加了3%。总体上，florbetaben结合增高的患者中有75%进展至阿尔茨海默病，而低水平结合患者中有19%进展至其他类型痴呆。对同一个体的MR影像学检查提示，基线时有海马萎缩的患者中53%进展至阿尔茨海默病。基线时同时有florbetaben结合增高和海马萎缩的患者中，80%在2年后进展至阿尔茨海默病。

根据这两项研究的结果，如果MCI患者大脑中b淀粉样蛋白斑块与药物的结合增高，则66%~75%将进展至阿尔茨海默病，如b淀粉样蛋白结合检测为阴性，则仅有不足20%将进展至另一种类型的痴呆。

Rowe医生披露自己参加了多家研发淀粉样蛋白影像产品公司的研究，包括Avid Radiopharmaceuticals、拜耳先灵、GE医疗和阿斯利康等公司。他还接受了拜耳和GE公司提供的咨询费。


Longitudinal tracking of the deposition of beta-amyloid over a period of 2-3 years with the use of PET imaging radiotracers in patients with mild cognitive impairment can help predict progression to Alzheimer’s disease or reliably rule it out as a diagnosis.

Those results, reported in two studies of the investigational agents 11C-Pittsburgh compound B (PiB) and 18F-florbetaben at the annual meeting of the Society of Nuclear Medicine and Molecular Imaging in Miami, showed that the tracers could be used to predict progression to Alzheimer’s in 66%-75% of those with elevated binding of the agents to beta-amyloid plaques in the brains of individuals with mild cognitive impairment (MCI). In cases where an individual tested negative for elevated beta-amyloid binding, fewer than 20% progressed to another type of dementia.

Results such as these show that detecting beta-amyloid burden in the brain “can help lead to diagnosis of Alzheimer’s disease when a patient has mild symptoms rather than wait until they have established dementia as is the current clinical practice. This may have important benefits for the patient, for their family, and for society,” said Dr. Christopher Rowe, the lead investigator on the PiB study and senior investigator on the florbetaben study.

The PiB study, called the Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing, included 92 patients with MCI. At baseline, Dr. Rowe and his colleagues detected high PiB binding in 65% of MCI patients. After 3 years, 66% of MCI patients who had a positive scan for high beta-amyloid burden at baseline had been diagnosed with Alzheimer’s, compared with only 7% of MCI patients with a negative scan.

Other studies of PiB out to 6 years of follow-up have shown that patients accrue beta-amyloid at “an incredibly slow” rate of about 2% per year. “If you have a negative scan, you can be reassured that you’re not going to have Alzheimer’s disease for at least the next 10 years,” Dr. Rowe said at a press conference at the meeting.

Because the half-life of PiB is only 20 minutes, it is not suitable for clinical use. The 2-hour half-life of florbetaben and other 18F amyloid radiotracers make them much more cost effective for clinical use, noted Dr. Rowe, director of the department of nuclear medicine and the center for PET and a consultant neurologist to the memory disorders clinic at the Austin Hospital in Melbourne, Australia.

The florbetaben study involved 45 patients with MCI who received PET imaging with the compound. At baseline, 53% had a high level of neocortical binding, and binding increased 3% after 2 years in those with already high levels. Overall, 75% of patients with elevated florbetaben binding progressed to Alzheimer’s disease, whereas 19% of those with a low level of binding progressed to other kinds of dementias.

MR imaging in the same individuals indicated that 53% of patients with hippocampal atrophy at baseline had progressed to Alzheimer’s. When the combination of high florbetaben binding and hippocampal atrophy was present, 80% had progressed to Alzheimer’s after 2 years.

“We don’t say that everybody who’s got Alzheimer’s disease should have these scans because I don’t think that would be cost effective. But in selected scenarios, when they’ve seen a memory specialist, I think these can be very useful clinically,” Dr. Rowe said.

He said amyloid imaging agents such as florbetaben have two potential uses:

• In patients with established dementia when there is uncertainty about whether the patient has Alzheimer’s disease or frontotemporal dementia. He noted that this has therapeutic implications because some of the medications used to treat Alzheimer’s, such as cholinesterase inhibitors, can make behavioral symptoms worse in frontotemporal dementia.

• In patients with MCI who have seen a specialist who is not sure what the cause of the symptoms might be and wants to see if it might be Alzheimer’s instead of waiting years for dementia to develop. Because about 40% with MCI do not go on to develop dementia, amyloid imaging studies would be reassuring to those patients, Dr. Rowe said.

Guidelines from the Alzheimer’s Association and the Society of Nuclear Medicine and Molecular Imaging (which recently changed its name from the Society of Nuclear Medicine) will soon be available on the appropriate use of the imaging agents, Dr. Rowe said in an interview.

He disclosed that he has served as an investigator on studies for many of the companies developing amyloid imaging products, including Avid Radiopharmaceuticals, Bayer Schering Pharma, GE Healthcare, and AstraZeneca. He has also received payments for consulting for Bayer and GE.