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…. ”

30Aug2014 – A Pretty Good Day

This entry is part 5 of 10 in the series "Liam's Battle" --

A pretty good day for Liam.

A pretty good day for Liam.

Liam is finally starting to act like himself. I can use a couple more days like this! He was playing and carrying on conversations with us for most of the day. While he was still in a lot of pain when he was moved (understandably), when he was being still, this is what he looked like. He hasn’t acted this coherent in weeks!

The pleural effusion appears to have been causing a considerable amount of pain.  I was told by the nursing staff that the teenagers that require a chest tube find it fairly uncomfortable. Since Liam is only two, it is difficult for him to describe his discomfort to us; however, if this is how he is acting with a chest tube in, I am guessing that the pleural effusion must have been very discomforting.

A few more good days like this will be real progress.  We need his strength to be up for Round 2 Chemo starting on Sept 10, 2014.

Pleural Effusion. Headed in the Right Direction?

This entry is part 4 of 10 in the series "Liam's Battle" --
Pleural Effusion

Pleural Effusion

So, those that have been following along this week know we have seemed to go downhill rather than up. Round One of Chemo was finished 24Aug2014. While the chemo seemed to be a non-event, these other complications have kept occurring one right after the other.

On Tuesday, he developed a rash for no real good reason. Initially, we thought that this might be due to one of the blood transfusions; however when the rash came back even stronger the following day after one of his medications, it strongly pointed to a possible allergic reaction to the drug. My understanding is that this is a preventative medication that is given during the chemo process to avoid a certain type of pneumonia developing while the immune system is weakened. It is a type of sulfa drug. I personally have had strong reactions to sulfa-drugs in the past, and while I am assured that the allergy to sulfa drugs is not genetically linked, sulfa drugs do often have strong allergic responses in people. So, while the rash is still dissipating, this is the strongest lead we have to go on. The medication has been switched to a different one, so we will see as time progresses forward.

Of biggest concern this week was when they were trying to wean him off of his requirement for [concentrated] oxygen, and they couldn’t. An X-ray showed us that he had developed a pleural effusion in his left lung. Initially, the fluid on ultrasound appeared to not be bloody (They would be able to see clotting). They decided that they would drain the fluid with a needle to see what it was.  Right before the procedure (or maybe it was during), an ultrasound this time showed that there was clotting. And sure enough, when they sucked the fluid out, it was bloody. Where was this fluid coming from? A CT was performed so that they could see the chemo port that was installed to determine whether the port site was bleeding or leaking into the space.  The CT showed that the port seemed OK.  This left us with a wait-and-see approach to the problem.  The only good explanation was that since he had been low on platelets, maybe he had spontaneously ruptured in the pleural space. They would wait until the next morning to see if the cavity had filled back up. If it had, they would do emergency exploratory surgery to:

  1. Find the source of the fluid
  2. Install a drain tube into the pleural space
  3. Possibly remove the port, just as a precuation

The next morning, 28Aug2014, an x-ray was performed.  The plerual effusion was back just as large as it had been the day before. Liam was headed for surgery as soon as it could be scheduled.

A little after 12PM, Liam was wheeled into surgery.  The surgery took about 90 minutes. They removed his port, just in case they missed something in the CT. They installed a drain tube into the pleural space, and they looked around for the leak with a camera.

They did not find one.

They sent the fluid for analysis to see if it contained Neuroblastoma, which we do not have the results for; however, whether or not it is there may not tell us much.

So what is going on?  Nobody knows!  But here is the best hypothesis that I heard in the debrief:

If the Neuroblastoma had made it into the pleural area, and the chemo had killed it, it is possible that the fluid and blood could be a response to the now dead Neurblastoma cells.  That would mean that the chemo is having an affect on the cancer and this whole plerual effusion business is a consequence of healing. Only time will tell.

This morning, 29Aug2014, an x-ray showed us that the pleural area is being drained effectively with the chest tube.  Now we wait for the body to heal the pleural area like it would heal a bruise anywhere else on the body.