匹兹堡化合物B：用于正电子发射断层扫描检测早老性痴呆早期病变

匹兹堡化合物B（Pittsburgh compound-B，PIB）是一种用于正电子发射断层扫描（positron emission tomography，PET）的新型显影药物，由美国匹兹堡大学（the University of Pittsburgh，PA，USA）的两位研究人员研制成功。这种化合物首次用于正电子发射断层扫描来检测早老性痴呆（Alzheimer’s disease，又叫作阿尔茨海默氏病）的早期病变。该化合物还有助于判断临床治疗是否抑制了或者终止了疾病的进展。

长期以来研究人员就认识到大脑的斑点沉积是早老性痴呆的特征性病变。但是多年以来，一直缺乏在活着的患者脑组织中鉴别该斑点的方法。一直到现在，研究人员只能通过尸体解剖取出患者大脑组织来进行研究。这种方法也是100多年前研究脑组织斑点沉积时首先采用的方法并沿用至今。

华盛顿大学（Washington University，St. Louis，MO，USA）放射学和精神病学教授Mark Mintun医学博士说：“在疾病早期阶段，当你打算开始治疗的时候，早老性痴呆的许多病变相当轻微。如果我们能够通过扫描来检测出早期形成的斑点，不但可以尽早开始治疗，而且也可能够在发生实质性损伤之前延缓或者终止斑点形成。”

匹兹堡化合物B结合在脑组织淀粉样斑点上。在没有淀粉样病变的患者，该化合物在30～60分钟内就被血流冲洗排出大脑；而在有淀粉样病变的患者，匹兹堡化合物B停留时间较长，在进行正电子发射断层扫描时产生强烈对比，病变很容易就能够被发现。

“如果检测为阳性，结果很容易被发现。”Mintun博士评论说。他目前正在华盛顿大学早老性痴呆研究中心（Alzheimer’s Disease Research Center，ADRC）主持一项新的正电子发射断层扫描研究项目。华盛顿大学的研究人员从2003年11月开始与匹兹堡大学的匹兹堡化合物B发明者进行合作，计划在华盛顿大学研制出一种安全有效的生产新化合物的方法。早老性痴呆研究中心从2004年5月开始使用这种新化合物进行正电子发射断层扫描。

匹兹堡化合物B的早期研究集中在那些已经明确诊断的早老性痴呆患者，以及那些没有任何感知损害症状的患者。“在出现临床症状之前就检查出危险人群，是我们利用匹兹堡化合物B所能做的最重要的事情。为了达到这个目标，确实需要一些象我们早老性痴呆研究中心这样的机构，以保证能够开展对患者进行以“年”为单位的随访。”Mintun博士如此评论说。

目前有许多设计用来冲洗脑组织淀粉样斑点的治疗方法，未来将综合研究匹兹堡化合物B在判断这些治疗精确性方面的问题。

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.