0:00
Good day everyone. My
name is Frank Lin.
I'm the Chief of the Targeted
Radionuclide Therapy Section or
the Molecular Imaging Program at
the National Cancer Institute
of the United States.
Today, I'll be speaking to
you about the current status and
future promise of targeted radioligand
therapy, or TRT for short,
for the treatment of cancers
of the prostate and others.
0:25
To give a brief
overview of my talk,
I will first go over the
basic concepts important for
our understanding of using
TRT as a cancer therapeutic.
Then, I will move into some background
information on prostate cancer
and how TRTs are already
being used in this space.
Next, I will have a more
expanded discussion on
one particular type of TRT
that is showing a lot of
promise and is generating
a lot of interest and
excitement in the prostate
medical oncology community.
Namely, TRT is based on
PSMA or prostate-specific
membrane antigen.
After the prostate
cancer discussion,
I will talk about other TRTs,
which have already
demonstrated good efficacy
and are in clinical
practice already today.
Then, I will finish up with
a brief discussion about
some promising future directions
the field of TRT
is moving towards.
1:16
First, let's talk
about the basics
of targeted
radionuclide therapy.
In today's modern age
of cancer treatment,
the idea of having a very
targeted treatment that is
specific for a particular type
of tumor cells is
very important.
While there are many
mechanisms that
provide the specificity
of treatment,
one of the cornerstone
concepts of
targeted therapy is the
idea that cancer cells have
a pattern or surface
receptors that
are characteristically
over-expressed
for that particular tumor type.
For example, many lung cancer
cells overexpress EGFR,
which stands for epidermal
growth factor receptor.
Many cancers of
neuroendocrine origin
in the gut overexpress on
their surface a receptor
for somatostatin or SSTR.
Physiologically, all of
these surface receptors
have something that
binds to them naturally,
such as the hormonal somatostatin
binding to the SSTR.
By chemically creating
a molecule that
mimics these receptors'
natural ligands,
you can create a drug that has
a binding property of
the original ligand.
You create a scenario
where you can
achieve very high
specific binding of
your drug to the tumor
cell of interest
that expresses a receptor
that you're targeting.
This concept of having a
binding ligand that can target
and specifically bind to
the matching surface
receptor on the tumor cell,
is one of the fundamental
frameworks of how
TRT agents work as a
cancer therapeutic.
By attaching a
radioactive molecule,
which is sometimes
referred to as
the payload of the drug
to this binding ligand.
You now have a way to
bring something that
is constantly emitting radiation
right up to and sometimes
internalizing into the tumor
cell that you want to kill.
The strength of the drug
will be determined by
the amount and type of radioactive
payload that is attached.
For instance, an isotope such as
Lutetium 177 emits a
lot of beta particles,
which can effectively kill
tumor cells when in
close proximity.
However, you can also attach
something like Actinium 225,
which emits a more powerful
alpha particle and can
kill a lot more tumor cells per
unit of radioactivity administered.
Now, there's clinical
consensus that
the effectiveness of
radiation at killing
cells correlates
strongly with a dose of
radiation that is given
or delivered to the cell.
That dose is determined
primarily by how
close and for how long you
get the source to the target.
An effective TRT drug does
both of these things well.
It can get the radioactive
payload close to
the tumor target via
matching receptor-like
impairing and have a
stay at the tumor for
a long time via receptor
internalization after ligand binding.
One bonus feature of
TRT agents is that you
can switch up the kind of
radioactive payload so that
instead of something that
gives therapeutic radiation,
you can then pass
something that gives off
other emissions
such as positrons,
which can then be picked up by
cameras like a PET scanner.
This will then allow you
to see in the body where
the TRT agents have gone and
this imaging drug can then
be used as a predictive marker
of whether your therapeutic drug
is going to get to
the tumor cells
of interest and
therefore be effective.
This is why sometimes
we refer to
TRT drugs as Theranostic,
which is a combination of
the words therapy and
diagnostic agent.
