thoughts on neutron capture therapies

[usernamesaredumb]

Mods: Please feel free to delete/move this thread if this is not the appropriate subforum.

I am an incoming M1 with a very heavy interest in radiation oncology, and I would like to get involved in researching new boron delivery methods for use with BNCT during my time in medical school and beyond.

As far as I know, BNCT is not in use anywhere in the U.S. and it seems like boron delivery is largest obstacle preventing its widespread usage.

Assuming something can be done about boron delivery, does this therapy really hold promise? Can this question even be answered yet? I spoke with a few rad-onc's at a large academic hospital who described BNCT as "the holy grail", which kind of took me aback. Is that an opinion that is widely held?

To take this one step further, what is the outlook on heavy particle/hadronic therapies as a whole? Are they just just an incremental improvement on XR therapy, or are they truly a "next generation"? I know PT seems to fall into the former category, not sure how CIRT and BNCT compare.

---

Members don't see this ad.

 

[PruritisAni]

This has been tried and tested perhaps dating back to the 70s. Boron has well-defined chemicophysical properties which would lend it well to bio or magneto-conjugated. It failed not due to delivery issues of B10, but rather, the non-negligible capture cross section of Hydrogen and Nitrogen which, as you know, is far from negligible. This is what limited neutron therapy, even sans boron, from the outset.
Gadolinium-neutron capture has also been proposed.

I could provide multiple references, but too lazy to look up. Though, like you, this topic also initially sparked my interest in RO. Good luck and keep the faith in the field.

 

[usernamesaredumb]

This has been tried and tested perhaps dating back to the 70s. Boron has well-defined chemicophysical properties which would lend it well to bio or magneto-conjugated. It failed not due to delivery issues of B10, but rather, the non-negligible capture cross section of Hydrogen and Nitrogen which, as you know, is far from negligible. This is what limited neutron therapy, even sans boron, from the outset.
Gadolinium-neutron capture has also been proposed.

I could provide multiple references, but too lazy to look up. Though, like you, this topic also initially sparked my interest in RO. Good luck and keep the faith in the field.

Off hand, do you know why GdNCT has not seen much attention? I understand the issues you stated will not be remedied by any choice of capture agent, but it seems like BNCT research is still rather robust whereas GdNCT research is practically non-existent even though Gd is pretty well-understood in terms of its biochemical properties

 

[PruritisAni]

Off hand, do you know why GdNCT has not seen much attention? I understand the issues you stated will not be remedied by any choice of capture agent, but it seems like BNCT research is still rather robust whereas GdNCT research is practically non-existent even though Gd is pretty well-understood in terms of its biochemical properties

Mechanism of decay after capture is essentially Auger electrons. Range is effectively on the order of the nucleus which is great if can get nuclear localization, but fundamentally LET is still 1, despite the increased density/probability of events. Therefore, this is presumably limited by the same factors as traditional XRT photons, electrons (oxygenation, primarily producing single strand breaks, etc). BNCT gets you that sweet, sweet alpha (and Li-nucleus!) which would presumably overcome hypoxia issues and tremendously increase double strand breaks thereby increase cell kill and tumor control probability.

 

[usernamesaredumb]

Mechanism of decay after capture is essentially Auger electrons. Range is effectively on the order of the nucleus which is great if can get nuclear localization, but fundamentally LET is still 1, despite the increased density/probability of events. Therefore, this is presumably limited by the same factors as traditional XRT photons, electrons (oxygenation, primarily producing single strand breaks, etc). BNCT gets you that sweet, sweet alpha (and Li-nucleus!) which would presumably overcome hypoxia issues and tremendously increase double strand breaks thereby increase cell kill and tumor control probability.

Thanks again

 

[Brim]

Mechanism of decay after capture is essentially Auger electrons. Range is effectively on the order of the nucleus which is great if can get nuclear localization, but fundamentally LET is still 1, despite the increased density/probability of events. Therefore, this is presumably limited by the same factors as traditional XRT photons, electrons (oxygenation, primarily producing single strand breaks, etc). BNCT gets you that sweet, sweet alpha (and Li-nucleus!) which would presumably overcome hypoxia issues and tremendously increase double strand breaks thereby increase cell kill and tumor control probability.

This thread (and your user name) has got me itching to start using BNCT in my practice.

 

[emt409]

There are one or two centers or Japan that still research BNCT. There have been some developments in heavily boronated compound development which do increase the therapeutic ratio with regard to the neutron flux required to deliver tumoricidal doses but mitigate dose from the nitrogen capture dose. However, operating a neutron source is not trivial, and the treatment has just not shown itself to be a cost effective therapy especially photon and proton therapies continually get better and better.

 

[usernamesaredumb]

There are one or two centers or Japan that still research BNCT. There have been some developments in heavily boronated compound development which do increase the therapeutic ratio with regard to the neutron flux required to deliver tumoricidal doses but mitigate dose from the nitrogen capture dose. However, operating a neutron source is not trivial, and the treatment has just not shown itself to be a cost effective therapy especially photon and proton therapies continually get better and better.

Do you see CIRT gaining steam, or is it just a minimal improvement on PT that does not warrant the increased cost?

 

[emt409]

Not at current cost levels. Just an interesting novelty available at a handful of centers throughout the world. Don't get me wrong, I'm a nuclear engineer by schooling originally, with extensive background in particle beam physics...I love heavy ion therapy, but there needs to be only about one center per continent.

 

[usernamesaredumb]

Not at current cost levels. Just an interesting novelty available at a handful of centers throughout the world. Don't get me wrong, I'm a nuclear engineer by schooling originally, with extensive background in particle beam physics...I love heavy ion therapy, but there needs to be only about one center per continent.

Thanks again. Last question I promise... Any advice for an incoming M1 who has their heart set on matching RO?

 

[medgator]

Thanks again. Last question I promise... Any advice for an incoming M1 who has their heart set on matching RO?

Hope you enjoy working in non coastal and/or rural underserved settings

 

[usernamesaredumb]

Hope you enjoy working in non coastal and/or rural underserved settings

fine by me

 

[emt409]

Hope you enjoy working in non coastal and/or rural underserved settings

Start studying for USMLE’s early, get high grades. Get involved in publishable reseach by your first summer of med school.