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Radiolabeling

melange

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When it comes to neuropsychopharmacology/chemistry I am an amateur at best, so forgive me if my questions sound layman.



My question is this - Is it possible to radiolabel any drug? I know a little bit how radiolabeling works but can someone with a more in depth knowledge shed some light on the actual imaging process.
 
When it comes to neuropsychopharmacology/chemistry I am an amateur at best, so forgive me if my questions sound layman.
My question is this - Is it possible to radiolabel any drug? I know a little bit how radiolabeling works but can someone with a more in depth knowledge shed some light on the actual imaging process.

yes almost any drug can be radiolabelled, drugs with fluorine are particularly useful as PET is an effective in vivo imaging tool. 14 C can replace any carbon, though the synthesis can be tedious, and 3H (tritium) is very useful for replacing a hydrogen. the only proviso is that the labelled position has to stay on the drug, so some hydrogens are useless because they will fall off.

A lot of radiolabelling is to do with detecting metabolites in urine and blood etc, a sample is taken and the labelled drug and its metabolites show up in a chromatographic technique, TLC or HPLC most commonly, and almost all the techniques or measuring receptor affinity use radiolabels. very little of it actually is used to image the drug inside a creature (human or otherwise)
 
To kinda quote / paraphrase Shulgin, "to plot the in vivo course of a biochemical that cannot be followed, It must be labeled somehow, with a radioactive element, but nature demands that it is one that is not a normal part of its makeup. So he says, I would like to follow this drug through the darkness of the body but I cannot see it as there is no light. I will attach a brilliant radioactive label to it, something like an iodine 125, so I can follow it as it goes here and there. The iodine is the light that the drug molecule is carrying, and the light can indeed be followed, but it is a different molecule. It is a completely different guide."

I think that somewhat sums up the critical problem inherent to using radio labeling.
 
To kinda quote / paraphrase Shulgin, "to plot the in vivo course of a biochemical that cannot be followed, It must be labeled somehow, with a radioactive element, but nature demands that it is one that is not a normal part of its makeup. So he says, I would like to follow this drug through the darkness of the body but I cannot see it as there is no light. I will attach a brilliant radioactive label to it, something like an iodine 125, so I can follow it as it goes here and there. The iodine is the light that the drug molecule is carrying, and the light can indeed be followed, but it is a different molecule. It is a completely different guide."

I think that somewhat sums up the critical problem inherent to using radio labeling.
inherent???
I don't think so.
there is no difference in chemistry between tritium chemistry and protium 1H ordinary hydrogen or the chemistry of carbon 14 and carbon 12.
and it makes no difference if radioactive fluorine replaces a fluorine already in a drug, for example labelled Beta CFT
125I DOI has exactly the same pharmacology as ordinary DOI

so it is up to the skill of the chemist,
 
inherent???
I don't think so.
there is no difference in chemistry between tritium chemistry and protium 1H ordinary hydrogen or the chemistry of carbon 14 and carbon 12.
and it makes no difference if radioactive fluorine replaces a fluorine already in a drug, for example labelled Beta CFT
125I DOI has exactly the same pharmacology as ordinary DOI

so it is up to the skill of the chemist,

Touche, perhaps my source is dated, or referring to a situation where there is no suitably similar position for the tag to replace.
 
inherent???
I don't think so.
there is no difference in chemistry between tritium chemistry and protium 1H ordinary hydrogen or the chemistry of carbon 14 and carbon 12.
and it makes no difference if radioactive fluorine replaces a fluorine already in a drug, for example labelled Beta CFT
125I DOI has exactly the same pharmacology as ordinary DOI

so it is up to the skill of the chemist,

Sorry to be pedantic, but technically that's not entirely correct. Changing the mass of the atoms involved in the bond does effect the potential energy well and vibrational frequencies of that bond, as well as the vibrations of the molecule as a whole to a degree.

Now, this will probably not have any effect in any practical sense as you only see this isotope effect if that bond is somehow involved in a rate limiting step of a reaction. And it only changes the kinetics of the reaction, not the general reactivity.

Nonetheless, if breaking of that bond or changing the hybridization of the heavier atom is involved in a degradation pathway for that compound you could possibly see some changes in the elimination half-life of the compound, and therefore it's duration of effect.
 
Sorry to be pedantic, but technically that's not entirely correct. Changing the mass of the atoms involved in the bond does effect the potential energy well and vibrational frequencies of that bond, as well as the vibrations of the molecule as a whole to a degree.

Now, this will probably not have any effect in any practical sense as you only see this isotope effect if that bond is somehow involved in a rate limiting step of a reaction. And it only changes the kinetics of the reaction, not the general reactivity.

Nonetheless, if breaking of that bond or changing the hybridization of the heavier atom is involved in a degradation pathway for that compound you could possibly see some changes in the elimination half-life of the compound, and therefore it's duration of effect.

indeed true and GSK have just wasted a shitload of money on a company that is busy making deuterated analogs of a load of patent drugs.
but I predict that the difference will not be significant enough for the FDA and once again the morons that run GSK will have burnt a shedload of money for no return.
but for general purposes of this thread and this forum it is an irrellevance.
 
there is no difference in chemistry between tritium chemistry and protium 1H ordinary hydrogen or the chemistry of carbon 14 and carbon 12.
and it makes no difference if radioactive fluorine replaces a fluorine already in a drug, for example labelled Beta CFT
125I DOI has exactly the same pharmacology as ordinary DOI

At least when it comes to tritium, I would partially disagree. Tritium is a beta-radiator, which isn't exactly the healthiest stuff on earth, in particular when ingested.

As long as we count 'toxicology' as a part of 'overall-pharmacology', tritium does make a difference. Colleague of mine is working with 3H-labeled guanine. You can easily imagine when this stuff gets incorporated into a DNA fragment...ouch!

For 13C, 125I and 18F I don't see any immediate problems though.

- Murphy
 
32P labelled psilocybin anyone?
35S labelled 2-CT-7?

I think a psychoactive dose of 32P labelled psilocybin would begin killing you before you came down. 50 nanoliters of a relatively dilute solution of labelled ATP screams so loud on a geiger counter it is scary. You could drink buckets of tritium before it reached the toxicity of a minute amount of 32P or even 35S.

Amazingly, I'm listening to NPR right now and they are doing a story on a tritium leak at one of the canadian nuclear reactors! They apparently leaked a shitload into the Ottawa River. Awesome.

I thought one of the Iodine isotopes used a bunch was a positron emitter? Or was that the bromine isotope shulgin used for the DOB study?
 
Nah, none made it to the river. Didn't really make it anywhere really, unless this is old info.

Is this from the plant that makes the medical isotopes I've been hearing so much about?

By Jo Ann Hustis - [email protected]
Exelon Nuclear is digging deep today for the source of a tritiated water leak at Dresden Generating Station at Morris.

The incident – discovered via a monitoring well on Tuesday, June 2, and officially confirmed Thursday, June 4 – is confined within the station site. This is the second incident of its kind for Dresden, which successfully capped off and replaced a leaking pipe in December 2006.

Other monitoring wells at the plant indicate no tritiated water beyond the plant site, Dresden spokesman Bob Osgood noted today.

“We took immediate action to verify what we found as part of our regular environmental monitoring program,” he said. “Nothing has left the property, testing at the mouth of the river and perimeter of the plant property shows.”

The monitoring well sample tested at tritum levels of 3.2 million picocuries per liter of water, and 17,500 picocuries per liter in adjacent monitoring wells, indicating virtually no spread of tritiated water underground, he said.

“We said, ‘Oh, oh, something’s wrong here,” he said of the monitoring well sample. “So, we did more sampling. The 3.2 million reading we got from a monitoring point that’s tested twice a year. Based on that, we knew this is where we should dig.”

Tritium is a naturally occurring isotope of hydrogen that emits a very low level of radiation, and is found in more-concentrated levels in water used in nuclear generating stations.

Both the Nuclear Regulatory Commission and Exelon have gone on record stating public health and safety have not been jeopardized by the release, nor are the safety and welfare of Dresden employees at risk.

The leak is in an area outside the reactor building and near the administration building, where several pipes are located six to seven feet underground. The pipes move tritiated water from the reactor to large condensate storage tanks.

The well was routinely tested about a month ago, and it was fine, Osgood said. These wells are sampled on a monthly basis.

Osgood said not much tritiated water is in the excavation around the pipes. What’s there is being removed.

“We’re sucking out the water in the excavation and holding that in storage tanks,” he said. “We will process this water like we do all other water. We haven’t yet been able to quantify the amount of water involved, but we know its not too much.”

The discovery is not affecting operation of the station.

Osgood said work crews have excavated the pipes today and are going about two feet deeper into the ground to attach an ultrasound device to detect any leaks and thinning of the pipe walls.

He did not term the leak as a major incident, saying it is probably smaller than similar leaks in 2004 and 2006, when Exelon replaced a length of pipe in the same general location.

“But, we take all leaks seriously,” he said, noting some media coverage to date is indicating this is not a major incident.

Viktoria Mytling, spokesman for Region 3, Nuclear Regulatory Commission in Lisle, said today the present leak is in about the same location as the previous incidents.

“They are now trying to identify the source of the leak,” she said. “They’re taking readings in other monitoring wells, and there is no indication of any kind of movement of tritium levels.”

Mytling said there is no underground course for elevated tritium levels to move offsite from Dresden Station.

She said other monitoring wells, which would show any movement of groundwater, are located between the well where the discovery was made and the outer regions of the property.

Cleanup of the tritiated water site depends on where the leak originated.

“I cannot tell you how they will remediate the tritium leak,” she said. “It’s something you have to talk to the utility about.”

Exelon spokesman Craig Nesbit said the leak was found fairly quickly, confined to the center plant site, and is being characterized at this time.

“The tritium wasn’t there the last time we checked,” he said. “We’re confident we can fix it pretty quickly. There are a lot of pipes in that area we have to excavate and check.”

Dresden is reworking the station’s underground pipe program, which is designed to find leaks and potential problems – finding deterioration before a leak starts.

Nesbit said the material in the underground pipes should last as long as that in the rest of the station’s equipment.

“Underground pipes are something we don’t expect to replace,” he said. “Otherwise, they wouldn’t be underground.”

Copyright © 2009 Morris Daily Herald. All rights reserved.
 
Fair enough, the story I heard was much more fanatical and perhaps I heard that one of their "options" is to release it into the river. I wasn't listening intensely as I was typing on here :)
 
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