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…. ”

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.

 

Diagnosis

This entry is part 1 of 10 in the series "Liam's Battle" --

On Sunday 17 Aug 2014, Liam was diagnosed with Neuroblastoma.  This was after a month of fussiness that could not be explained.

Six weeks prior to this diagnoses, we had a normal, almost 2 year old.  When he started being fussy, we figured that he was sick, but nothing that a kid his age might be expected to get. He was fussy in the middle of the night, and this really caught us off-guard. He has always been such an easy going kid — He was sleeping through the night at 12 weeks. So what was going on?

We started noticing that their were bulges in his testicular sack. Hernia!  He must be  fussy because of an inguinal hernia. Knowing how painful that can be from my own personal experience, we got him to his PCP as soon as possible. She agreed that we should see a surgeon.  I immediately scheduled a consultation at Children’s Medical Center in Dallas, and we were seen in short order. Once seen, the doctor agreed, and we had him in for surgery the very next day.

Once inside to repair the hernia, the surgeon found no real evidence of an inguinal hernia. We were told that what we must have been seeing were large veins in the testicular sac. We accepted this, but really did not question from that point that the fussiness could be something else.

The three days following the operation, Liam was doing pretty well. He had had a local anesthetic which helped numb any pain from the surgery.  We thought we had whatever this was beat… Then the fussiness started again. After about a day of this, we called a nurse. A likely culprit: constipation.  So, we loaded the kid up with miralax for several days until the Poo ran clear. Still fussy.  A couple more days later, I called a nurse again. The thought  at that time was that that maybe he wasn’t eating, and that was causing his bowels to not be working correctly. Give more Tylenol and Motrin — ease his comfort from the surgery so that he can eat.

He seemed better while well stocked on the pain meds, but I kept thinking to myself, “This seems like a lot of pain medicine for just a hernia operation”

Around his birthday, he developed a black eye. Those bigger siblings of his must have been playing rough with him. So of course, a scolding was in order on the etiquette of being gentle with their baby brother.

As the next week rolled by. More bruising developed on his legs, and his color was turning pale. He looked normal to me, but he was turning paler by the day so slightly I wasn’t noticing.

The fussiness continued throughout the day and throughout the night.

It wasn’t until Liam had a chance to spend the night with relatives while Jenn and I went away for an evening to celebrate our anniversary that the grandparents had the chance to notice that something was off and the bruising didn’t seem right to them.  When they returned him to us, they voiced their concerns. I watched Liam as we fed the kids pizza that night. He ate a couple of bites and his belly became super distended. It was already looking pretty large. “Maybe there is something going on that is unrelated to the surgery,”  I thought.  Right then and there I decided that I would take him to the ER. Jenn had been working with him at this point and had dosed him again with pain meds. He fell asleep pretty soon after.

“Well, if he wakes up in the night I will take him then,” I thought. I want him to get his rest.

Sure enough at about 3:55AM, he stirred us awake. I loaded him up in the car and drove to Children’s Medical Center in downtown Dallas.  I had been thinking all night that he must have a blockage in his bowel. It was time for an X-ray. Let’s shine some light through this problem.

There was no one in line at the ER at Children’s at about 4:45 when I got there.  I was seen pretty fast. Imaging was occurring faster than at any other time I have ever been to the ER.

About an hour and a half later a doctor came in my room and announced that they had found a mass above the kidney.

In that moment, I felt relieved. There had been a reason that my calm and peaceful boy had been so fussy.

In the next moment, the name of the cancer that it was most likely to be (because of how it was presenting) was announced to me: neuroblastoma. I had never heard of it. Which is probably why I did not freak out like they were expecting me to.

So after they left the room, I googled it. This is what I found: Less than 50% survival rate when in the high risk category.

I called Jenn, “They found a mass on his right adrenal gland atop his kidney.  You need to get up here.”