New MR Contrast Agents. The Devil you know vs the Devil you don't know.

This blog deals with my assessment of superparamagnetic iron oxide particulate agents as MR contrast agents. It is highly compacted- but can be extrapolated to the entire field of MR contrast, and perhaps everything else in life.

I had not seen this article before (a review on SPIO MR agents), because it is written in an obscure journal that a radiologist would not have ready access. In part I say this because one has to pay attention to the audience and how likely they are to see an article > hence should they have known.. Take this exactly as it reads and extend it to everything else we are dealing with.

That being said, I like it, it is brief and describes the degree of thought that has gone into these agents for the purposes they were developed for.

None of them took hold because the imaging features of Gd were always considered superior - perhaps in large measure because easier to interpret, in large measure again because Gd is used on T1 weighted images, which can look close to as good, pretty, as CT images. So they generate images that look like contrast enhanced CT but with more information. Generally all radiologists, young and old, can read CT. In 2-3 sentences that also summarizes everything that is crucial to know about Gd vs other agents.

Now that you see a brief description of particle size and a limited description of other properties, like coating of the molecule in this review article... We have to compare that to feraheme, and how it was constructed, particle size, coating, etc. Feraheme actually was first named Ferumoxyl and was originally intended as an iron-based MR angiographic contrast agent.

The other thing that has killed many stupid MR agents is the cost - cost is a huge issue. A clinical dose of feraheme is something like $600.. That is twice the entire charge of MRI in most countries in the world. One of the agents I quickly realized critical to torpedo is PFOB, an oral agent that resulted in signal void in the GI tract, but had weird sensation in the mouth, and came out as explosive uncontrolled diarrhea in many (it could not be controlled in the mouth, and also in the back-end). Cost per patient dose $600. My humorous take on that was for $100 you could buy a bottle of Dom Perignon, and if you gave the patient just 3 glasses that would be $50 - stopper the Dom and save the remaining 3 glasses for the next patient. The patient would then go back to the referring doctor and tell them: "that MRI was the best test I ever had". After PFOB, the reporting back to the referring doctor would be: "that is the worst test I ever had, never send me back for another MRI". Radiologists' business depends on happy referring doctors which mainly depends on satisfied (even better happy) patients reporting back to doctors, who then will refer more patients to MRI. So 3 glasses of Dom - tons of future patients; 1 dose of PFOB, the MR unit is standing idle.

The other at least as major problem we have right now is we do not have ready access to studying these agents on an MRI in patients. None of us are presently supervising director of MRI in a university center. Let alone, supervising director with the energy and courage to pursue this.

What is ideal for the my team to do is to gather knowledge and information. Succinctly this article tells us about 3 purposes these iron agents were designed for, so we can think of these when evaluating iron agents or all other agents:

1. MRA. Feraheme seems to have good effect for this - how does it compare to GBCA enhanced MRA, maybe more importantly noncontrast agent MRA.

2. lesion detection in solid organs - now SPIOs have been developed/emphasized for liver lesions - but this is too small a market to be profitable for a company. Resovist ideal because it gives MRA info, dynamic enhancement to observe vascular supply of liver lesions, and late RES uptake. But only improvement in liver is not sufficient to command any market... and expanding into other organs has been limited.

3. lymph node evaluation: malignant vs benign. This seemed to be the most unique ability of only a few USPIO agents... The comparator though (comparators are always important) is PET imaging (then combined with PET-CT or PET-MR).

So an iron agent has to do at least 2 of the above things to be useful. Feraheme seems to do at least pt 1... but then how does it compare to noncontrast MRA? which is no extra cost and no additional risk beyond MRI.

The other thing with non Gd agents is safety. How do we know it will be any safer than Gd? I doubt dysprosium should be appreciably safer.. It becomes a little like: devil you know vs devil you don't know.

And then the ultimate killer - 100 million +, to get a drug FDA approved. 3 phases of investigation. Who has that money? Who wants to take that risk?

All that being said - and we have to know all those points cold.. which means we have to know all those points cold... if we want to pursue other agents...

This is however completely different than pursuing the knowledge of other strategies/agents> this we must keep doing and always do.

Richard Semelka, MD