Now you go further away into space, of course, the dose that you receive increases as well. And so when we try to look a little bit the comparison, of course, the radiation type is a little bit different. Of course, we have alpha particles that are very similar, but what is an element that is very different and important for space research is the heavy ions. So especially for the relative biological effectiveness, heavy ions such as ion has a RBE of 20-40, which is not found for RLT. However, there is still low dose, but it's a little bit different of low dose because it's chronic and with the RLT, it's more continuous based on the decay, but of course the absorbed dose is very different. And so when we talk about radiosensitivity for space, we are looking mostly on cancer risk assessment, while for RLT we are looking for toxicity. So the question is as well, why radiosensitivity varies between individuals? And we had a great talk just here a few minutes ago when we look at DNA repair and signaling capacity, as well as some genetic syndromes and variants. We saw ATM, BRCA1/2, and so on. If we go a little bit further to the cellular and tissue level factors, you have cell cycle regulation.
We just saw that as well. And of course the cell types that actually proliferate and have a cell turnover much higher are of course more radiosensitive to that. And then of course the tumor microenvironment has quite an impact as well on how the cells are behaving. Going even further to the organism level factors, you have age. Sex seems to be some indication that the immune response and the hormonal modulation of DNA repair has an impact on radiosensitivity and as well the general health, epigenetic, and the lifestyle has quite some impact as well. And so everybody behaves a bit differently, has a different life. So we have a tendency to have a different response to radiation. Now, this is of course interesting as well for when we have the astronaut selection process. However, we need to know that when the selection goes on, there is a pre-selection of highly healthy candidates. So for example, in 2024, the NASA, there were 8,000 candidates, only 10 candidates were selected to go to the next phase for the two-year training.
So that means as well already there, we have a population that is extremely healthy and goes into space. There is no test that is actually being performed on radiosensitivity being part of the selection process. However, after that, the knowledge about it is quite useful for biomonitoring and as well to adapt based on the mission protocol because yeah, if you have a tendency to be more radiosensitive, you might not go directly outside the vehicle for your mission. But there is a big part of research being done and we are lucky that astronauts are very open to be compliant in a certain way to give to the science to us. And so here we have as well a publication from us where we assess the radiosensitivity and biomonitoring into space radiation. And I will go through it a little bit so that you understand what is potentially useful for radioligand therapy. So the first one, it's the chromosomal aberration assay. This is known since the 1960s. It's really a gold standard. We have very beautiful images, fluorescent images where we see translocation, dicentric, and different changes into the chromosome. This is all about more the use of blood samples and the evaluation of peripheral blood nuclear cells. Besides this assay, you have as well the Comet assay. This is based on electrophoresis and basically the tail tells you how much DNA damage there is. And you can see based on the increased dose that indeed the tail is increasing, but there are some limitations to it as well.
The chromosome aberration takes quite some days to do it. The comet assay goes much quicker, but you cannot go to all the doses that you wish to go. Then more in vitro as well, the clonogenic survival assay, this is a gold standard to assess the RBE and really measures the productive cell that after the fine radiation doses. And so you can see that higher the dose, of course, less cells are surviving. And based on the different radiosensitivity, you have different responses. And then something that is more and more in use is the omic-based signature. And that is very useful as well, especially when you integrate multiple types of omics. And then the GeneLab actually is a project where it's very nice that there is a repository of all the data that is generated, whether it is from astronauts, from in vitro, academic research as well. And basically this is a really rich database that you can use to evaluate the effect of radiation and to look into elements that could explain radiosensitivity. And this is something that we did as well where we can see that different persons are actually responding differently based on certain gene signature. And this potentially can be used to evaluate the radiosensitivity.
We use as well this kind of gene signature, for example, to estimate how much dose a person received. For example, we received random samples from different institution where we didn't know which dose the samples these PBMCs were receiving. And by just this signature, we could actually identify what dose they received. So this is quite of interest. Then lastly, there's something that is very known as the gamma-H2AX/53BP1 foci assay. And basically, this is something that we did as well with astronauts. We took blood samples before they went into space, after they went to the space and we evaluated as well, the DNA damage and repair kinetics. And basically we can see as well how people are actually responding to it. And one of the limitations of it as well is, for example, with high-LET, you have difficulties of being able to properly quantify the DNA foci. That's why we are currently looking into developing the expansion microscopy methodology with actinium-225 PSMA to see indeed if we can improve the quantification and as well have a predictive tool to know how much a person would respond in terms of radiosensitivity. And this is just an animation where we actually try to automate the quantification to go faster. Now, this is all nice, but how can we translate that into a radioligand therapy?
It's especially the work of Widjaja that is really showing that actually in a prospective study with 20 patients that they evaluated these gamma-H2AX and 53BP1 foci that kind of predict a little bit how a person is going to respond to the treatment based on the radiosensitivity. If you have low baseline levels of these proteins, you have more tendency of have a poor outcome. So it's very interesting that these things potentially can be used as well into a clinical application. And then there will be in a few minutes as well, a very interesting talk about these circulating tumor cells. So I will not go into details, but this is as well a potential avenue. Now, this is the question as well, how can we improve? It's not always easy. Liquid biopsies is one point, but you of course as well take biopsies before you do any kind of imaging and then treatment. You have as well now a big of a chunk of imaging technologies that are coming where we can do as well the culture of organoids, organ on a chip, and as well digital twin. And there as well for us, we are currently developing all the protocols that are needed to actually on PD cell, patient-derived cell lines to have these organoids and actually as well with radioligand therapy and to properly quantify what are these effects, efficacy and binding and so on. So that a little bit concludes my presentation. There is quite some potential. We have a lot of knowledge in the past from which techniques were used, but the gamma foci is one of them potentially in liquid biopsies is very promising.
Then just to advertise the extreme work of my colleague Irina Primac, we did really a comprehensive overview of all the current landscape of targeted radionuclide therapy, and the link there is to get free access. So thank you very much.