匹茲堡化合物B（Pittsburgh compound-B，PIB）是一種用于正電子發(fā)射斷層掃描（positron emission tomography，PET）的新型顯影藥物，由美國(guó)匹茲堡大學(xué)（the University of Pittsburgh，PA，USA）的兩位研究人員研制成功。這種化合物首次用于正電子發(fā)射斷層掃描來(lái)檢測(cè)早老性癡呆（Alzheimer’s disease，又叫作阿爾茨海默氏病）的早期病變。該化合物還有助于判斷臨床治療是否抑制了或者終止了疾病的進(jìn)展。

長(zhǎng)期以來(lái)研究人員就認(rèn)識(shí)到大腦的斑點(diǎn)沉積是早老性癡呆的特征性病變。但是多年以來(lái)，一直缺乏在活著的患者腦組織中鑒別該斑點(diǎn)的方法。一直到現(xiàn)在，研究人員只能通過尸體解剖取出患者大腦組織來(lái)進(jìn)行研究。這種方法也是100多年前研究腦組織斑點(diǎn)沉積時(shí)首先采用的方法并沿用至今。

華盛頓大學(xué)（Washington University，St. Louis，MO，USA）放射學(xué)和精神病學(xué)教授Mark Mintun醫(yī)學(xué)博士說(shuō)：“在疾病早期階段，當(dāng)你打算開始治療的時(shí)候，早老性癡呆的許多病變相當(dāng)輕微。如果我們能夠通過掃描來(lái)檢測(cè)出早期形成的斑點(diǎn)，不但可以盡早開始治療，而且也可能夠在發(fā)生實(shí)質(zhì)性損傷之前延緩或者終止斑點(diǎn)形成。”

匹茲堡化合物B結(jié)合在腦組織淀粉樣斑點(diǎn)上。在沒有淀粉樣病變的患者，該化合物在30～60分鐘內(nèi)就被血流沖洗排出大腦；而在有淀粉樣病變的患者，匹茲堡化合物B停留時(shí)間較長(zhǎng)，在進(jìn)行正電子發(fā)射斷層掃描時(shí)產(chǎn)生強(qiáng)烈對(duì)比，病變很容易就能夠被發(fā)現(xiàn)。

“如果檢測(cè)為陽(yáng)性，結(jié)果很容易被發(fā)現(xiàn)。”Mintun博士評(píng)論說(shuō)。他目前正在華盛頓大學(xué)早老性癡呆研究中心（Alzheimer’s Disease Research Center，ADRC）主持一項(xiàng)新的正電子發(fā)射斷層掃描研究項(xiàng)目。華盛頓大學(xué)的研究人員從2003年11月開始與匹茲堡大學(xué)的匹茲堡化合物B發(fā)明者進(jìn)行合作，計(jì)劃在華盛頓大學(xué)研制出一種安全有效的生產(chǎn)新化合物的方法。早老性癡呆研究中心從2004年5月開始使用這種新化合物進(jìn)行正電子發(fā)射斷層掃描。

匹茲堡化合物B的早期研究集中在那些已經(jīng)明確診斷的早老性癡呆患者，以及那些沒有任何感知損害癥狀的患者。“在出現(xiàn)臨床癥狀之前就檢查出危險(xiǎn)人群，是我們利用匹茲堡化合物B所能做的最重要的事情。為了達(dá)到這個(gè)目標(biāo)，確實(shí)需要一些象我們?cè)缋闲园V呆研究中心這樣的機(jī)構(gòu)，以保證能夠開展對(duì)患者進(jìn)行以“年”為單位的隨訪。”Mintun博士如此評(píng)論說(shuō)。

目前有許多設(shè)計(jì)用來(lái)沖洗腦組織淀粉樣斑點(diǎn)的治療方法，未來(lái)將綜合研究匹茲堡化合物B在判斷這些治療精確性方面的問題。

Imaging Agent Detects Plaques in Alzheimer’s Patients

A new positron emission tomography (PET) imaging agent, known as PIB (Pittsburgh compound-B), was developed by two investigators at the University of Pittsburgh (PA, USA). This compound was first used with PET scanning to evaluate the earliest stages of Alzheimer’s disease (AD). It also may help in the development and evaluation of treatments to suppress or halt the condition.

Researchers have long understood that plaque deposits in the brain are characteristic of AD, but a method to identify them in living individuals has remained elusive for many years. Up till now, researchers have been able to identify the plaques only by postmortem retrieval of brain tissue, the technique that first led to the discovery of brain plaque about 100 years ago.

“In the early stages when you would want to start treatment, many of the changes of Alzheimer’s disease are actually fairly mild. If we could detect the early development of the plaques with a scan, we’d not only be able to start treatment sooner, we might even be able to slow or stop the development of the plaques before substantial damage occurred,” said Mark Mintun, M.D., professor of radiology and psychiatry at Washington University (St. Louis, MO, USA)

PIB adheres to amyloid plaques in the brain. In an individual lacking amyloid, the agent washes out of the brain in 30 to 60 minutes; in an individual with amyloid, PIB remains longer, creating a strong contrast that PET scans can pick up easily.

“When this test is positive, it’s dramatically visual,” remarked Dr. Mintun, who is heading a new a PIB study at Washington University’s Alzheimer’s Disease Research Center (ADRC). Washington University researchers started working with the University of Pittsburgh creators of PIB in November of 2003 to develop a safe and effective method for production of the new agent at Washington University. The ARDC began to use the new agent for PET scanning in April of 2004.

Early research into PIB’s potential will concentrate both on those already diagnosed with AD and on others without any symptoms of cognitive impairment. “Identifying people at risk before they develop clinical symptoms of the condition is one of the most important things we may be able to accomplish with PIB. To do that, it’s really crucial to have an ADRC like ours where we can follow people on a yearly basis,” stated Dr. Mintun.

Future research of PIB may incorporate testing its accuracy as an assessment of new treatments designed to flush amyloid from the brain.