Iofetamine

[indelibleface]

http://en.wikipedia.org/wiki/Iofetamine

This is a bizarre analog of both isopropylamphetamine and p-iodoamphetamine that is used in neuroimaging (hence the radioactive iodine isotope in place of the standard iodine atom).

The question is this: how do they get away with using this drug for diagnostic procedures if there is potential for neurotoxicity? Are the doses sufficiently low so the risk is negligible? I wonder how much of any radiolabeled drug they would need to use for this purpose to get a quality image.

 

[sekio]

I would imagine the low dose, p-isopropyl group (reducing affinity for monoamine release somewhat), and lack of regular use (how many SPECT scans can you reasonably expect to get in a year?) all contribute to its "safety".

p-iodoamphetamine is the "least" toxic of the p-haloamphetamines (excluding p-fluoroamphetamine), so I think that works in its favour too.

 

[indelibleface]

I would imagine the low dose, p-isopropyl group (reducing affinity for monoamine release somewhat), and lack of regular use (how many SPECT scans can you reasonably expect to get in a year?) all contribute to its "safety".

p-iodoamphetamine is the "least" toxic of the p-haloamphetamines (excluding p-fluoroamphetamine), so I think that works in its favour too.

That said, it begs the question--why this molecule for this purpose, I wonder?

 

[sekio]

For nuclear imaging, you'd need a radioactive atom to emit some sort of energy. Iodine is a pretty popular one because it can be fairly easily stuck onto aromatic rings. (c.f. iodomelatonin and such). You'd also want it to localise to wherever you're inspecting. An iodinated amphetamine fits the bill nicely for this purpose.

The wiki article says it's for cerebral blood perfusion imaging, that is, measuring where blood is flowing in the brain, and how much. Used to diagnose strokes and e.g. where seizures occur in the brain. It is given by injection and the radiation can be measured by e.g. CT scans.

I would imagine that when it comes down to being able to gauge severity of strokes/seizures, and a little oxidative damage, the oxidative damage is acceptable.

Radiolabeled amines, such as I-123 iodoamphetamine, are lipophilic compounds, which are extracted by the brain proportional to blood flow. Scintigraphic maps of regional cerebral blood flow can therefore be obtained using commercially available radionuclides and standard single photon emission computed tomography instrumentation. I-123 iodoamphetamine imaging, therefore, permits the detection and assessment of altered perfusion in neurologic diseases, such as cerebral infarction and epilepsy.

http://www.ncbi.nlm.nih.gov/pubmed/2655294
http://www.ncbi.nlm.nih.gov/pubmed/6811496

Another fun compound is ioflupane/DATScan, an iodinated cocaine/RTI analogue! That's gotta be a real kick in the pants to get scanned with.

 

[ebola?]

Yeah, but why would you want a broad-spectrum monoamine releaser for that type of scan? Wouldn't you instead want a radio-labeled ligand specific to the anatomical region you're examining? DATScan is highly selective for DAT (well, duh! It's in the name ) and thus makes more sense to me.

Another fun compound is ioflupane/DATScan, an iodinated cocaine/RTI analogue! That's gotta be a real kick in the pants to get scanned with.

Well, no hospital will actually have enough on-hand for someone to achieve noticeable effects, let alone dose someone sufficiently to achieve such in a single scan.

ebola

 

[sekio]

I think if you're measuring blood perfusion, it doesn't really matter what you use. A broad spectrum, lipopilic, monoamine releaser that nonspecifically distributes to the brain is probably more useful for perfusion studies rather than a compound that will selectively accumulate in certain parts of the brain.

Apparently formication (feeling bugs under your skin) is a side effect of DATscan ... usage. So maybe it *is* bioactive.

 

[Hammilton]

Apparently fornication (feeling bugs under your skin) is a side effect of DATscan ... usage. So maybe it *is* bioactive.

LOL

I think you mean formication!!! Fornication involves skin, but in a different way. A better way, imho.



I think DATScan is usually used to look at dopamine transporter levels, so clearly it is active. However there are dopamine transporter ligands that bind slightly differently and have high affinities but only limited ability to actually block dopamine from binding as well. I'm not sure if DATScan is one of these, actually I don't think it is. some of the GBR compounds fall into this category to a degree, I think. They were all invented in the search for a cocaine antagonist: a drug that would bind to the same site in a way that would antagonize cocaine's effects without blocking dopamine. A cool idea, but one that hasn't been implemented therapeutically. I think there is a drug with decent affinity for DAT but doesn't produce addiction. I can't remember what it is though... I think it's also a muscarinic drug... or an old Parkinson's drug. Damn this is really bugging me.

And with these drugs, aren't they mostly used to look at where they end up, not at oxygen usage (which can be measured independent of a drug using the BOLD effect)? They're used specifically because they will accumulate in specific areas depending on where they bind. I don't know why this drug is used or how it was chosen. I suspect there was a good reason.

Actually reading more, it looks like this is used in PET and SPECT scans because it is so lipophillic and is used to look at the structure, not the function of the brain.

I suppose in this case a drug that ends up everywhere is best. You don't want holes in your image, unless they're actually lesions. In which case you do want to see them...

Anyway, I don't think it's used very often any more. I imagine this sort of thing is mostly replaced by fMRI and the various types which use highly specific ligands.