chemistry

Pittsburgh compound B

Pittsburgh compound B is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Pittsburgh compound B rather than just read about it. In short: Pittsburgh compound B (PiB) is a radioactive analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue. Due to this property, Pittsburgh compound B may be used in investigational studies of Alzheimer's disease.

Key takeaways

Pittsburgh compound B belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Pittsburgh compound B to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Pittsburgh compound B from memory before moving on to harder problems.

Reference excerpt

Pittsburgh compound B (PiB) is a radioactive analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue. Due to this property, Pittsburgh compound B may be used in investigational studies of Alzheimer's disease.

History The definitive diagnosis of Alzheimer's disease can only be made following the demonstration of the presence of beta-amyloid (Aβ) plaques and neurofibrillary tangles, the pathologic hallmarks of Alzheimer's disease in brain tissue, typically at autopsy. While the cognitive impairments of the disease could be monitored throughout the disease course, clinicians had no reliable way to monitor the pathologic progression of the disease. Due to this fact, a clear understanding of the process of amyloid deposition and how amyloid deposits relate to the cognitive symptoms of Alzheimer's disease remains to be elucidated. While sophisticated centers for the treatment of Alzheimer's disease are able to diagnose the disease with some reliability based on its clinical presentation, the differential diagnosis of Alzheimer's disease from other dementias is less robust. Furthermore, as novel disease-modifying therapies for Alzheimer's disease that attack and remove beta-amyloid deposits from the brain enter clinical trials, a pre-mortem tool for assessing their effectiveness at clearing the amyloid deposits was a much needed development. To answer these needs, a research team from the University of Pittsburgh led by geriatrics psychiatrist William E. Klunk and radiochemist Chester A. Mathis synthesised charge-neutral benzothiazoles derived from thioflavin T, which included a small number of compounds with suitable properties for use as a positron emission tomography imaging agent. One of these compounds, 2-(4'-[11C]methylaminophenyl)-6-hydroxybenzothiazole, was tested in human subjects. The University of Pittsburgh team partnered with a team of researchers from Uppsala University in Uppsala, Sweden, to conduct the first trials of this new agent in human research subjects. As this was the second investigational compound of this class sent to Uppsala from the University of Pittsburgh group, it was termed simply Pittsburgh compound-B by the Swedish team, who also abbreviated it as "PiB".

The first PiB study of a human subject with a clinical diagnosis of Alzheimer's disease was conducted by Henry Engler in February, 2002, at Uppsala University. PET scans showed that the compound was retained in areas of the cerebral cortex known to contain significant amyloid deposits from post-mortem examinations. The initial human study of PiB was expanded to include 16 Alzheimer's disease subjects and 9 cognitively normal controls, the report of which was published in 2004 in the Annals of Neurology. Since that initial study, PiB has been adopted as a research tool by other research institutions. In addition, GE Healthcare is pursuing the development of a clinical diagnostic agent based on PiB for assessing brain amyloidosis.

Alzheimer's disease research 11C-PiB is currently the most studied and used radioligand for PET imaging of cerebral Aβ pathology. This technique has been implicated in Alzheimer's disease research whereby scientists involved in this field are able to perform noninvasive in vivo neuroimaging studies using PET scans in brains of individuals with various degrees of dementia. The 11C-Pittsburgh compound B (11C-PiB) radiotracer is used to measure regional 11C-PiB binding retention rates, thus allowing for the visual and quantitative measurement of Aβ deposition. 11C-PiB is a fluorescent derivative of thioflavin T which preferentially targets and binds to fibrillar Aβ forms found in dense core plaques with high affinity and specificity. In particular, it specifically binds to Aβ40 and Aβ42 fibrils and insoluble plaques containing the aforementioned Aβ peptides. PiB does not bind with great affinity to soluble or nonfibrillar Aβ plaques until plaques have reached a crucial magnitude, which has yet to be determined. Furthermore, this radiotracer does not bind to neurofibrillary tangles (NFTs) in the neuronal regions of the brain during postmortem autopsies. A typical injected dose ranges from 250 to 450 MBq and the imaging time normally varies between 40 and 90 minutes. The quantification of 11C-PiB has demonstrated to elicit a profound difference in neuronal cortical binding between individuals recognized with Alzheimer's disease and age-matched cognitively normal controls.

Published clinical research studies

See also Florbetapir Florbetaben Flutemetamol Tafamidis List of PET radiotracers

References

Further reading Puchtler H, Sweat F, Levine M (1 May 1962). "On the binding of Congo red by amyloid". J. Histochem. Cytochem. 10 (3): 355–364. doi:10.1177/10.3.355.. Brain amyloid can be shown by staining brain sections with thioflavin S or Congo red. Morgan DL, Dunnick JK, Goehl T, Jokinen MP, Matthews HB, Zeiger E, Mennear JH (1994). "Summary of the National Toxicology Program benzidine dye initiative". Environ Health Perspect. 102 (supp 2): 63–78. doi:10.1289/ehp.9410263. PMC 1567082. PMID 7925189.. Some azo dyes such as Congo red, may be carcinogenic. Cerniglia CE, Freeman JP, Franklin W, Pack LD (1982). "Metabolism of benzidine and benzidine-congener based dyes by human, monkey and rat intestinal bacteria". Biochem Biophys Res Commun. 107 (4): 1224–1229. doi:10.1016/s0006-291x(82)80128-9. PMID 6814437. Intestinal bacteria convert Congo red to carcinogenic free amine.

Illustrations

Worked examples

Example 1 — a first encounter with Pittsburgh compound B

Start with the simplest possible case. Write down what Pittsburgh compound B claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Pittsburgh compound B before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Pittsburgh compound B ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Pittsburgh compound B

In research: Pittsburgh compound B appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Pittsburgh compound B in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Pittsburgh compound B is common in secondary-school and first-year university syllabi. It links to neighbouring topics Alzheimer's disease, Benzothiazoles, Hydroxyarenes, so understanding it makes those chapters shorter.
In everyday life: Look for Pittsburgh compound B outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

Affiliate

Preply — study more efficiently by working with a personal tutor. 50% off.

How to study Pittsburgh compound B in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Pittsburgh compound B means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Pittsburgh compound B out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Pittsburgh compound B in simple terms?

Why does Pittsburgh compound B matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Pittsburgh compound B?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Pittsburgh compound B.