A newer faster machine might deliver at four gray per minute. And within this range, would we expect any difference in clinical outcome? Absolutely not. We think that of this range being equal. There is one type of dose rate exploration that's ongoing and that's flash radiation, which is very, very high dose rates, still experimental and has not changed clinical practice. So at the end of the day, dose rate in external beam has not led to any changes in clinical practice. But what has is fractionation or how we prescribe the radiation. And this is expressed in total dose and dose per fraction. And just like dose rate, there is an element of time here. And the purpose of fractionation is to spare normal tissue, both acute responding tissue and late responding tissue. And for the same total dose, if you increase the dose per fraction, you increase the biologically effective dose.
And that means that if you can squeeze in higher doses of radiation in single fractions and spare normal tissue, you're going to have higher cell kill and more efficacy. So the key takeaway for external beam, dose rate hasn't really had a clinical impact, but fractionation is very, very important. So now when we look at external beam and radiopharmaceuticals, there are many differences between these modalities. The first obvious difference, external beam is a local therapy. Radiopharmaceuticals are systemic therapies, but the dose rates are also different. So external beam, you're delivering that dose over minutes to seconds. With radiopharmaceuticals, even with your shortest lived isotopes, you are still delivering that dose over days. And there's also an important difference in terms of how the dose is distributed. In external beam, we have physicians prescribing a dose of radiation to a specific volume of tissue, and that dose is deposited in a very homogeneous way.
Doesn't matter what targets are expressed, doesn't matter what tissue type is there, the dose is delivered. On the other hand, with radiopharmaceuticals, the physicians are prescribing and administered radioactivity, and then the dose is distributed based on target expression biodistribution. It's inherently very heterogeneous, both at the macroscopic and the microscopic level. These two differences, dose rate, dose distribution lead to differences in biologic effects. And this is why we can't take the standard external beam dose tolerances that we all know and love and apply them to radiopharmaceuticals. There are some similarities. Both types of radiation primarily use DNA damage to kill the cancer cell. There are off-target effects, and then both types can augment the immune system, both the systemic immune response, but also at the level of the tumor microenvironment. And just like when you give chemo with external beam, you can increase the rate of cure. It makes sense that radiopharmaceuticals are going to be better in combinations as well. So I mentioned that there's a difference in dose rate, external beam and radiopharmaceuticals. Radiopharmaceuticals is much lower, but it's also just much more complicated.
The isotope half-life is important, but we need to match the half-life with the kinetics of the binder. For example, if the half-life is too short, you can underdose slow binding targets. That being said, all other variables being equal, a shorter half-life should increase cell kill, but what's important here, the cell, meaning tumor, but also potentially normal tissue. The particle type matters. For alphas, for example, we're giving bigger punches, but the RBE of five is what we use generally. We don't really understand fully the RBEs and it's going to depend on the type of tissue that we're looking at. The kinetics, I think are arguably the most important component of dose rate where the dose is actually being delivered in the body. And unlike external beam, the dose rate here depends on residence time and biodistribution of your drug. And we're looking at integrated exposure, so time-activity curves of tumor relative to normal tissue to really optimize your therapeutic window. And then the target is also important. So if you have a high and stable target expression, you're going to be optimized for high dose rate to the tumor itself.
So how do we maximize the therapeutic window with radiopharmaceuticals? So radiation's great. It's a highly cytotoxic payload. It can kill any cell as long as you deliver it precisely enough. But I mentioned that kinetics and biodistribution are really critical in defining the therapeutic window of radiopharmaceuticals. We have to think about how long does it take the drug to get to the tumor? What about the other organs? How long does it stay there? And then the half-life and the particle type should be linked to these characteristics to optimize clinical benefit. And then just like with dose rate and external beam, I think tweaking the half-life of an isotope is probably not where we're going to get the biggest bang for our buck. We should be looking at how we prescribe these drugs in terms of dose and schedule and use clinical data to really help us understand how to best optimize.
Now, if we will move beyond PSMA and going into other novel targets, at AstraZeneca, we really think that you're going to need multiple binder formats to get there, so all the way from small molecules to large full-length antibodies. And so AstraZeneca's portfolio really leverages this diversity. For some targets, small molecules are great, like PSMA. It has a small well-defined binding site. On the other end of the spectrum, you might need an antibody if your target is difficult to localize and you really need high specificity and longer half lives to get the dose in the tumor. And then you have in between peptides, mini bodies and antibodies, et cetera. So the music hasn't started yet, so I can do my shameless plug for what we're doing at AstraZeneca.
First of all, we have a new term in the field, not to add confusion to an already confusing sort of alphabet soup of terms, but we refer to radiopharmaceuticals as radioconjugates. And why is that? It's really that diversity of binder is what we're getting at because radioligand therapy can imply small molecule. And at AstraZeneca, we believe that we have the key components to discover, develop, and also manufacture radioconjugates. So here's our pipeline. We just heard about our actinium PSMA that's in development currently. We have two assets in phase-one. One is an EGFR/c-MET bispecific, and the other is a STEAP2 antibody, the difficult to target STEAP2, hence the antibody. And then we have a number of undisclosed targets as well.
This is a little bit about AstraZeneca's bold ambition in solid tumor. So the idea is we want to drive functional cures in patients across all disease states of solid tumors. And how do we get there? This is a color wheel that highlights all of the different modalities that we have in our pipeline for oncology. And we really believe that to develop these transformational regimens, they're going to have to be done in combination. So for radioconjugates, we're looking at small-molecule DDRi inhibitors, as well as drugs that can augment the immune system as well. And then this is my last slide, but I don't have a conclusion slide. So in the absence of a conclusion slide, I will summarize my conclusions again. Does dose rate matter? Yes, but it's more than just the half-life of the isotope. It's very complicated. We need to match the right isotope with the right binder, the right target, and then just like in external beam, we're pushing the envelope and increasing rates of cure by altering fractionation.
And in the same way, I think we should really look at dose optimization of radiopharmaceuticals as well. With that, I have some time left.