POSITRON EMISSION TOMOGRAPHY TECHNOLOGIES AND CAPABILITIES AT YALE

Transcript

• 00:00Okay. So, my name is
• 00:02Chi Liu. I'm a professor
• 00:03in radiology and one of
• 00:04the associate, directors of the
• 00:06Biomedical Imaging Institute. I'm gonna
• 00:08introduce Doctor. Mark Normanton as
• 00:10the next speaker. Doctor. Normanton
• 00:11graduated from University of Rhode
• 00:14Island with a bachelor degree
• 00:15in electrical engineering and biomedical
• 00:17engineering
• 00:18and earned his PhD in
• 00:19biomedical engineering from Purdue.
• 00:22Then he completed a postdoctoral
• 00:23training at Yale School of
• 00:24Medicine and also a center
• 00:26here before joining the faculty
• 00:28at the Harvard Medical School
• 00:29and MGH.
• 00:30In twenty twenty four, he
• 00:31returned to Yale as associate
• 00:33professor and also the director
• 00:35of the PET Core. And
• 00:36he's going to give us
• 00:37an overview of PET imaging
• 00:39technologies and capabilities.
• 00:47Thank you, Chi.
• 00:49So in the next,
• 00:52few minutes, I'll give you
• 00:53sort of an overview of,
• 00:55pet imaging,
• 00:57starting with the research workflow,
• 00:59talk a little bit about
• 01:00the resources that we have
• 01:01here at Yale, and then
• 01:02give some examples of the
• 01:04types of studies that we
• 01:05do with them.
• 01:06So just to orient you,
• 01:09the,
• 01:10the the typical workflow that
• 01:11we have, in our studies
• 01:13starts with on-site production of
• 01:15a radioisotope,
• 01:16in our local cyclotron.
• 01:18That radioisotope
• 01:20is,
• 01:21incorporated,
• 01:22into a molecule of interest
• 01:23in our radiochemistry
• 01:25facilities.
• 01:26That radiopharmaceutical
• 01:27is injected into a research
• 01:29subject could be,
• 01:30an animal,
• 01:31could be a human,
• 01:33could be a plant in
• 01:34some cases,
• 01:36believe it or not.
• 01:38And then with,
• 01:40our cameras,
• 01:41we acquire data, reconstruct images,
• 01:43and then do analysis to
• 01:45get quantitative,
• 01:47physiological
• 01:48parameters.
• 01:52Okay.
• 01:53So, with that as sort
• 01:54of a general context,
• 01:57I'll give a few highlights
• 01:58of the Yale Petcorp.
• 02:00The facilities were opened,
• 02:02in two thousand and six.
• 02:04We have an on-site cyclotron
• 02:06and
• 02:07a good manufacturing
• 02:08practice,
• 02:09certified,
• 02:10radiochemistry
• 02:11facility.
• 02:12To date, sixty eight radio
• 02:14tracers
• 02:15have been administered to human
• 02:16subjects,
• 02:17fifty eight of those were
• 02:18made in house,
• 02:20and many more in animals,
• 02:23have been tested so far.
• 02:26As mentioned, we do,
• 02:27human and,
• 02:28preclinical imaging,
• 02:31about, over twelve thousand scans
• 02:33to date in in human,
• 02:35and the eight thousand is
• 02:37actually
• 02:37an estimate on non human.
• 02:39I think as of this
• 02:41morning we are
• 02:42up to seven thousand nine
• 02:43hundred and ninety nine to
• 02:45be exact.
• 02:47Many of these studies also
• 02:49involve,
• 02:50Arterial Blood Sampling. You may
• 02:52ask what is that all
• 02:53about?
• 02:54And the idea is that
• 02:55in order to quantify what
• 02:56is going on in the
• 02:57tissue, we have to understand
• 02:59what got delivered to the
• 03:00tissue.
• 03:01Subject of a different talk.
• 03:04And we have everything needed,
• 03:07including veterinary,
• 03:09clinical support,
• 03:10to to handle all of
• 03:12this and post processing,
• 03:15for for all of the
• 03:16data that we acquire.
• 03:18Our physical layout,
• 03:21is essentially,
• 03:23three different,
• 03:24vertical layers in adjacent buildings,
• 03:27primarily at the,
• 03:28intersection of Howard Ave and
• 03:30York Street.
• 03:32In the,
• 03:33the sort of the, but
• 03:35the hub of this is
• 03:36the Cyclotron and Radiochemistry
• 03:38Facility.
• 03:40We'll see that in a
• 03:41little bit more detail in
• 03:43a moment.
• 03:44Adjacent to that, we have
• 03:45animal imaging facilities,
• 03:47and proximal animal housing,
• 03:50and
• 03:52in vertical layers,
• 03:54right next to that, We
• 03:56have human imaging,
• 03:58both above
• 03:59and below.
• 04:02Okay, so returning to this
• 04:04kind of orienting slide,
• 04:06let's take a
• 04:10sorry, this is not advancing.
• 04:12There we are. So let's
• 04:14take a closer look at
• 04:15radiochemistry,
• 04:16and what we have available.
• 04:18Some pictures just to prove
• 04:19that this stuff is real,
• 04:21this is, our
• 04:23on-site cyclotron,
• 04:26where we produce radioisotopes.
• 04:28We have a number of
• 04:29different automated and manual synthesis,
• 04:32units,
• 04:33for making,
• 04:34different radio traces.
• 04:36Those are then sent off
• 04:38to the quality control lab
• 04:39where we make sure that
• 04:40what we made,
• 04:42is what we thought we
• 04:42made, and is,
• 04:45pure and ready to to
• 04:47send out for animal or
• 04:48human use.
• 04:50And this is all supported
• 04:51by,
• 04:52cold chemistry facilities
• 04:54that make all the precursor
• 04:55and standard materials
• 04:57needed to do the radio
• 04:58labeling.
• 05:00I will obviously not read
• 05:01the slide, but just a
• 05:02highlight of,
• 05:04the dozens of different radio
• 05:05tracers that have been used
• 05:06in, human studies to date
• 05:08here at Yale.
• 05:10A vast majority of these
• 05:11are targeting different,
• 05:13neuroreceptors,
• 05:15metabotropic,
• 05:16ionotropic,
• 05:17transporters,
• 05:19as George mentioned,
• 05:21pioneering work has been done
• 05:22here for imaging, synaptic density.
• 05:26We also,
• 05:27do a lot of imaging
• 05:28in the context of, neurodegeneration,
• 05:32for misfolded proteins,
• 05:34and a growing number of
• 05:35cancer biomarkers as well.
• 05:39This slide highlights,
• 05:41some of the more recent,
• 05:43compounds that have come online.
• 05:45The top row, these are
• 05:46five tracers that have been
• 05:48recently
• 05:49authorized by the FDA to
• 05:51move on to human subjects.
• 05:53This slide is actually already
• 05:54out of date.
• 05:56Two of the ones that
• 05:57are listed as pending
• 05:59have since graduated to the
• 06:01top row
• 06:02and we have several others
• 06:04in the bottom row
• 06:05that are
• 06:07at various stages of development,
• 06:10awaiting human use.
• 06:14Because that list is constantly
• 06:16in flux, and growing, I'd
• 06:18encourage you to visit our
• 06:19website where we, maintain what
• 06:21we try to keep a,
• 06:23an up to date list
• 06:24of, of what's been approved.
• 06:28Okay.
• 06:29Next, let's talk about the
• 06:31imaging side of things.
• 06:33So, our preclinical imaging,
• 06:36consists of four different,
• 06:39imaging systems.
• 06:40We have two,
• 06:44lost my cursor,
• 06:45two on the left, older
• 06:47generation,
• 06:48dedicated pet,
• 06:50scanners for animal subjects.
• 06:52In the middle,
• 06:54this is a high resolution,
• 06:56high sensitivity,
• 06:57animal system that was recently
• 06:59installed
• 07:00and is currently undergoing,
• 07:03site qualifications,
• 07:05and on the right a
• 07:06companion system,
• 07:08that actually is,
• 07:11for image for doing SPECT
• 07:12imaging,
• 07:13within the Pet Center.
• 07:17On the human imaging side,
• 07:19we have
• 07:20four scanners as well.
• 07:22The top two these are
• 07:23whole body systems,
• 07:25so you can
• 07:26image anything from from head
• 07:28to toe.
• 07:29The bottom two are dedicated
• 07:31brain systems.
• 07:33Bottom left, the Siemens, or
• 07:34ECAT HRRT,
• 07:36is an older generation system.
• 07:38It was the state of
• 07:39the art,
• 07:42brain PET scanner up until
• 07:44relatively recently,
• 07:46and that was supplanted by
• 07:47the NeuroExplorer
• 07:49shown on the bottom right.
• 07:50And with that, I'll segue
• 07:52a little bit into some
• 07:53of the applications.
• 07:55The NeuroExplorer
• 07:56was constructed
• 07:58in a consortium
• 07:59led here at Yale by
• 08:00Rich Carson,
• 08:02and together with UC Davis
• 08:03and United Imaging,
• 08:05won many awards, has outstanding
• 08:08images,
• 08:09as you can see here,
• 08:10comparing in the top right
• 08:12NeuroExplorer brain images,
• 08:15to the previous state of
• 08:17the art HRRT.
• 08:20The NeuroExplorer is good not
• 08:22just for,
• 08:23brain imaging. This is, some
• 08:25head and neck cancer imaging,
• 08:27led by Takhto Yanaga and
• 08:29colleagues,
• 08:30and we can see in
• 08:31comparison to the,
• 08:33state of the art, clinical
• 08:34scanner, the vision, we're able
• 08:36to see nodules that, were
• 08:38previously missed.
• 08:41Couple of examples from Dave
• 08:43Mutosky's lab,
• 08:44looking at Parkinson's disease,
• 08:47and looking at, dopamine transporters
• 08:49and synaptic density,
• 08:52in the in the course
• 08:52of pathology.
• 08:55We do a lot of
• 08:56methods development.
• 08:57This is
• 08:59an acquisition protocol that's being
• 09:02tested,
• 09:03where instead of having a
• 09:04subject undergo a long two
• 09:06hour scan,
• 09:07we would instead
• 09:09acquire a few minutes of
• 09:10data, allow the subject to
• 09:12come off and have a
• 09:13break, and then come back
• 09:14onto the scanner,
• 09:15for a late acquisition period.
• 09:18And we're getting results that,
• 09:20are in strong agreement with
• 09:21doing the complete acquisition,
• 09:24and is more practical for
• 09:25both, subject and staff.
• 09:28Not everything that we do
• 09:29is in human subjects. Shown
• 09:31here is an example,
• 09:32from Ruth Asch,
• 09:34and Irina Sturlus's group,
• 09:37doing,
• 09:38synaptic density imaging in a
• 09:40rodent model,
• 09:41of chronic unpredictable stress,
• 09:43and correlating,
• 09:45those measures of synaptic density
• 09:47to different behavioral measures.
• 09:49Not everything that we do
• 09:51is, even in the brain.
• 09:54Jason Beany's group is focusing
• 09:56on endocrine function,
• 09:58and a large portion of
• 09:59that, imaging the pancreas and
• 10:01diabetes.
• 10:04Here's an example
• 10:06that is particularly well suited
• 10:07to PET MR, which is
• 10:08a technology that will be
• 10:10coming soon,
• 10:12and this combines PET and
• 10:14MR
• 10:15in a synergistic fashion
• 10:17to measure mitochondrial membrane potential
• 10:20in absolute units.
• 10:23And not everything that we
• 10:24do is even PET, in
• 10:26the Pet Center.
• 10:27This is an example of
• 10:29some work that
• 10:31we've done previously and are
• 10:32looking to resume
• 10:34developing
• 10:35lutetium labelled nanoparticles
• 10:37that are selectively taken up
• 10:40in the stroma of
• 10:42tumours
• 10:44with good therapeutic effect.
• 10:47So that's a a highlight
• 10:48of some of the,
• 10:50different technologies that we have
• 10:51available in the pet center
• 10:53and a few of the
• 10:54applications,
• 10:56that are exemplary of the
• 10:57type of work that we
• 10:58do. Thank you.