MetaIodoBenzylGuanidine (mIBG) [update]

This entry is part 1 of 3 in the series "Radiation" --
MetaIodoBenzylGuanidine

MetaIodoBenzylGuanidine

[Update to the Update: On 24July2015 after his cancer had relapsed, another mIBG scan was performed. This time, the cancer was shown to be mIBG avid]

[Update: On 4Sept2014, during the imaging 123-mIBG, it was determined that Liam’s Neuroblastoma is one of the types that does not take up mIBG. This means that he will be excluded from participation of the 131-mIBG study and we will be performing more chemo treatments]

Let’s not leave out the cool science.  During the course of his treatment Liam will encounter mIBG (MetaIodoBenzylGuanidine).  The first time that he encounters it, should all go well, is this week (~4Sept2014). He will be injected with the chemical so that his Neuroblastoma can be imaged. So, how does it work? It turns out that Neuroblastoma has a strong affinity for this compound in about 85% of cases.[1] In a very high percentage, the Neuroblastoma cells will take this compound up while the normal cells will not. This is called ‘selectivity’. (i.e. the Neuroblastoma soaks this compound up selectively over normal cells).  mIBG in itself, however, doesn’t do anything. It is taken into the cell, and then is excreted from the cell at a later time.  This means that the Neuroblastoma cells are not sensitive to the compound. 

A clever and ingenious pupil of chemistry can already see what to do next.  Swapping out the Iodine atom on this compound with the radioactive version  makes this molecule very useful.


[123]-Iodine

123 Iodine will decay by electron capture to form 123 Tellurium which will then emit a Gamma ray with an energy of 159 keV. This is useful for imaging.  This is like having an x-ray performed, but rather than having an x-ray source shining high energy light through Liam, the light will be generated inside him!  Since this radioactive atom is attached to a compound which is only selective to Neuroblastoma, Gamma rays (like x-rays) will be generated only at the Neuroblastoma sites.  With the correct detector, the Neuroblastoma will light up like a Christmas tree.


[131]-Iodine

If 131 Iodine is used, different results will be observed.  131 Iodine decays in the follow two manners (statistically a 90% Beta(-) Decay and a 10% Gamma decay):

(Beta(-) Decay ~90%) {^{131}_{53}\mathrm{I}} \rightarrow \beta + \bar{\nu_e} + {^{131}_{54}\mathrm{Xe}^*}  + 606 keV 

(Gamma Decay ~10%) {^{131}_{54}\mathrm{Xe}^*}  \rightarrow {^{131}_{54}\mathrm{Xe}} + \gamma  + 364 keV

The Beta(-) decay produces a very energetic electron and an Antineutrino which have a tissue penetration of about 0.6 to 2 mm. This is enough energy to destroy cells. (i.e. a cell sized atomic bomb) So in essence, this gives a pathway for the mIBG, which is very selective to the Neuroblastoma, to blow up the cells (and leave the good cells alone)

This mIBG therapy is typically only given in cases of Nueroblastoma that have relapsed, however, we may be one of the lucky families that gets this treatment as a clinical trial directed at making this part of the standard treatment.  If everything works out well, we will be part of this trial sometime after 5 or 6 chemotherapy treatments.


This mIBG scan being performed this week will only involve 123 Iodine for gamma ray imaging. This will indicate all of the places that the Nueroblastoma has metastasized to. It will be used as a baseline for how he is progressing in his treatment later on.

  1. According to NationWideChildrens.org “…Roughly 80-85% of neuroblastomas will absorb MIBG. There are really 2 ways in which MIBG treatment is used. In both methods, the MIBG chemical is attached to an iodine molecule that has been made radioactive. The radioactivity can be either a low-dose or a high-dose…. ”

The PET Scan, a Chemist’s View

This entry is part 2 of 3 in the series "Radiation" --

Liam had a Positron Emission Tomography (PET) scan on 19Sept2014. For this the radioactive tracer is Fludeoxyglucose (18F) or (18F-FDG) for short. For those of you crazy chemistry people out there (like Jenn and myself), check this out:

a)Fludeoxyglucose b) β+ Decay of a proton emits a positron (and changes Fluorine to Oxygen); Since a positron is the antimatter equivalent of an electron, when it finds the closest electron it will annihilate. The matter will cease to exist, and it will turn into energy in the form of light (gamma rays). The two gamma rays produced each will have 511 keV of energy. c) With a little acid, the product will be glucose and continue through the energy cycle in the cell. Until the radioactive decay, the molecule is stuck. There is no chemistry available to the cell to process the glucose with substituted Fluorine, once the F gets converted to a hydroxyl, the chemistry can proceed as normal (With a heavy, but stable Oxygen atom)

The 18F-FDG looks just like the glucose molecule except for a heavy fluorine in place of the  2′ hydroxyl group.  Since all cells use glucose as a power source, the PET scan exploits the fact that cancer cells require more energy, and they will take up more of the compound than normal cells. The areas of the body emitting large amounts of gamma radiation are likely to have concentrations of cancer cells.

For those of you (and I know who you are) who would like even more information, here are some links that I found helpful when I was coming up to speed on the technique:

Fludeoxyglucose (18F)

Positron Emmision Tomography

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications (scroll down to figure 13)

Decay scheme of 18F

mIBG – We are back on!

This entry is part 3 of 3 in the series "Radiation" --

WARNING: Science Content


As with all my posts, I try to include some thought provoking science, as well as interesting water cooler talk.  Good luck.
 
MetaIodoBenzylGuanidine

MetaIodoBenzylGuanidine


[Prologue]

For those avid followers of all of the science that I have introduced during all of this, you will recognize that this post is a rehash, but an exciting rehash.

Early on, Liam was initially slated to participate in a mIBG (MetaIodoBenzylGuanidine) trial.  The trial wasn’t supposed to happen until after the induction period of chemotherapy.  The catch is that only 80-85% of neuroblastomas absorb mIBG.  This is why fairly soon after diagnoses, while there is still a lot of cancer in concentrated pockets throughout the body, an mIBG scan is given to see if the particular variety of neuroblastoma picks it up. This is done with [123]- mIBG (see below.)

When this scan was performed on Liam back in September, there had been problems and the scan was not performed right away.  The doctors and hospital staff were having difficulty stabilizing Liam.  In fact, that first session in the hospital lasted over 21 days.  He had been started on  a fantastic chemotherapy drug called Topotecan (which is a TopoIsomerase I inhibitor that is so darn cool, it deserves its own post and I will not discuss it here.)  The problem was that Liam was spiraling out of control while he was on it. He started having trouble breathing, and he ended up with a plural effusion (yep… that was a bad couple of days. Click here for the post from that day).  After all was said and done, the mIBG scan was pushed off until he was admitted for chemo round 2.

When the [123] mIBG scan was finally performed, it came back negative. We were bummed, but the chemo seemed to be going so well that we really didn’t give it much thought. Liam was feeling better.

After 6 rounds of chemotherapy, a follow up PET scan was performed. No cancer showed up on the scan. He had a remarkable response, and we thought we were doing pretty well.  In reviewing all that had happened over the course of 6 rounds of chemo, I wondered if most of the cancer had vanished just after the first round of chemotherapy.  If it did, it would have skewed the mIBG test to a negative result.

Looking back at the sudden improvement after round 1- the plural effusion (now believed to be caused by cancer dying his lungs) and all of the immediate weight loss (now believed to be the cancer dying in his abdomen)…. he looked normal for the first time in months; I contend that the Topotecan chemotherapy made most of the cancer disappear quickly.  His response even astonished his doctors.

Now that the cancer has come back,  it was suggested by the doctors at CookChildren’s that we look one more time at the mIBG.  So, we did, and it gave a positive response to mIBG.  It can clearly be seen in the left tibia and the pelvis.

mIBG Liam 24July2015

123-mIBG Scan of Liam on 24July2015. His neuroblastoma has soaked up the mIBG compound, and due to its radioactivity is exposing the film. His trouble spots in his left leg and pelvis can clearly be seen.

So what does this mean? It means that we now have a really awesome tool in our tool chest to fight this. It won’t cure the neuroblastoma, but hopefully we can knock it down and coupled with other therapies, we can get this disease under control for Liam.  This is an option that a week ago we did not have.

[End of Prologue]

So, how does it work? It turns out that Neuroblastoma has a strong affinity for mIBG in about 85% of cases.[1] In a very high percentage, the Neuroblastoma cells will take this compound up while the normal cells will not. This is called ‘selectivity’. (i.e. the Neuroblastoma soaks this compound up selectively over normal cells).  mIBG in itself, however, doesn’t do anything. It is taken into the cell, and then is excreted from the cell at a later time.  This means that the Neuroblastoma cells are not sensitive to the compound. 

A clever and ingenious pupil of chemistry can already see what to do next.  Swapping out the Iodine atom on this compound with the radioactive version  makes this molecule very useful.


[123]-Iodine

123 Iodine will decay by electron capture to form 123 Tellurium which will then emit a Gamma ray with an energy of 159 keV. This is useful for imaging.  This is like having an x-ray performed, but rather than having an x-ray source shining high energy light through Liam, the light will be generated inside him!  Since this radioactive atom is attached to a compound which is only selective to Neuroblastoma, Gamma rays (like x-rays) will be generated only at the Neuroblastoma sites.  With the correct detector, the Neuroblastoma will light up like a Christmas tree.


[131]-Iodine

If 131 Iodine is used, different results will be observed.  131 Iodine decays in the follow two manners (statistically a 90% Beta(-) Decay and a 10% Gamma decay):

(Beta(-) Decay ~90%) {^{131}_{53}\mathrm{I}} \rightarrow \beta + \bar{\nu_e} + {^{131}_{54}\mathrm{Xe}^*}  + 606 keV 

(Gamma Decay ~10%) {^{131}_{54}\mathrm{Xe}^*}  \rightarrow {^{131}_{54}\mathrm{Xe}} + \gamma  + 364 keV

The Beta(-) decay produces a very energetic electron and an Antineutrino which have a tissue penetration of about 0.6 to 2 mm. This is enough energy to destroy cells. (i.e. a cell sized atomic bomb) So in essence, this gives a pathway for the mIBG, which is very selective to the Neuroblastoma, to blow up the cells (and leave the good cells alone).


This mIBG scan that was performed today only involved 123 Iodine for gamma ray imaging (see above images). This indicates all of the places that the Neuroblastoma is, with a few exceptions. There are false readings in some of the places like the thyroid (which regulates Iodine containing compounds).    In the coming weeks, it’ll be time to bring out the [131] Iodine and give this cancer the radioactive punch it deserves.

  1. According to NationWideChildrens.org “…Roughly 80-85% of neuroblastomas will absorb MIBG. There are really 2 ways in which MIBG treatment is used. In both methods, the MIBG chemical is attached to an iodine molecule that has been made radioactive. The radioactivity can be either a low-dose or a high-dose…. ”