COVID-19 Vaccine and Pet Scans

October 18, 2021

Information

October 17, 2021

Yale Cancer Center

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email: canceranswers@yale.edu

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00:00Funding for Yale Cancer Answers
00:02is provided by Smilow Cancer
00:04Hospital and AstraZeneca.
00:08Welcome to Yale Cancer Answers with
00:10your host doctor Anees Chagpar.
00:12Yale Cancer Answers features the
00:14latest information on cancer care by
00:17welcoming oncologists and specialists
00:18who are on the forefront of the
00:21battle to fight cancer. This week,
00:22it's a conversation about nuclear
00:24medicine and cancer management with
00:26Doctor Darko Pucar. Dr. Pucar is
00:28an associate professor
00:30of radiology and biomedical imaging
00:32at the Yale School of Medicine,
00:34where Dr. Chagpar is a professor
00:37of surgical oncology.
00:40Darko, maybe we can start off by you
00:41telling us a little bit about
00:43yourself and about what you do.
00:45I am a nuclear radiologist.
00:48That means I have received training in
00:51general radiology and nuclear medicine.
00:53In my case I did that
00:54at Cornell and Sloan
00:56Kettering and I'm certified by the
00:58American Board of Radiology and
01:01the Board of Nuclear Medicine.
01:03I also have a science degree from
01:06Mayo Clinic and I provide clinical
01:08service and I conduct research
01:10in general nuclear medicine.
01:13and nuclear medicine therapy,
01:16and aeronautics,
01:16which I will explain in a minute.
01:19Let's breakdown
01:21some of those things,
01:24tell our audience a little bit more about
01:27what exactly is nuclear medicine.
01:30We do use radioactive
01:34tracers to detect cancer,
01:37monitor cancer, and treat cancer.
01:39So radioactive tracers are a chemical
01:42compound in which one or more
01:45atoms have been replaced by radioisotope
01:48in the process that we call labeling.
01:50So these chemical compounds are
01:52participants in body functions that
01:54are usually altered by cancer,
01:57and we have two options.
02:01One is to label the
02:03radioisotope with the gamma rays,
02:05in which case we can
02:07produce images or we can
02:09use radioisotopes that
02:11emit the high energy particles,
02:13in which case we can kill the cancer.
02:15It sounds like nuclear
02:17medicine has a role to play both in
02:20diagnostics as well as in therapeutics.
02:23So let's look at the diagnostics.
02:25To begin with, many of
02:27us have heard about PET scans.
02:29Is that really the main modality
02:31that's used in nuclear medicine
02:33for cancer and tell us a little
02:35bit more about how that works?
02:38Yeah, you are absolutely right.
02:40PET scans really are the main modality
02:43used for cancer diagnostics,
02:45and it's basically a hybrid machine
02:48or hybrid scanner that consists of
02:51the CT scanner which is X ray
02:53machine that produced 3D map of body
02:56density and of the PET scanner,
02:58which is basically a gamma ray
03:01detector machine that again gives
03:03us 3D map of tracer distribution
03:05in the body and then at the end
03:08you fuse CT and PET images to get images
03:11that show both anatomy and function in
03:15the normal tissue and in the cancer.
03:18Do all cancer patients get a pet CT?
03:21Or is this only for particular patients?
03:25Well, it would depend from cancer to cancer,
03:28but usually PET scans in most
03:31cancers but not in all I use for
03:34more advance patients with cancer.
03:36So those are the patients where
03:39the cancer is either very large locally,
03:42it is spread to the nodes nearby
03:44to the cancer site or has
03:47metastasized to distant body sites.
03:50And so the pet scan really gives
03:52us an idea of how far the cancer
03:54has spread. Is that right?
03:56Absolutely, and the
03:57main advantage of the PET scan is that it
04:00can detect very small lesions that
04:02are not visible on the conventional
04:04imaging like a CAT scan or MRI.
04:07But then you also mentioned that the
04:11same nuclear medicine technologies
04:12can be used in the therapeutic arena.
04:16So tell us more about that.
04:18Yeah, so this is very exciting development.
04:21I mean for years we have treated cancers,
04:24but it was mostly limited to the
04:27iodine treatment for thyroid cancer.
04:29But now we are getting many new exciting
04:32compounds for prostate cancer for
04:34the new rendering tumors and probably
04:37would spread to other cancers as well.
04:40There are two types of
04:43therapies that we conduct.
04:45One is if we use chemical
04:49compounds that image
04:51these high energy particles
04:53to kill the cancer,
04:55but we do imaging still with a
04:58conventional PET scan which
05:00usually maps the glucose.
05:02It's called fluorodeoxyglucose and
05:03then there is a new exciting process
05:06which is called theranostics in which
05:08we can use the same chemical compound
05:10which is important to the function of
05:12cancer which are labeled either
05:15with the isotopes that can be detected
05:18by gamma ray detectors and give us
05:22imagine or it can be labeled with a high
05:24energy particles and kill the cancer.
05:26So probably the most common
05:29examples that are probably even
05:31known to our audience is dotatate
05:36and is the treatment for neuroendocrine cancer.
05:38So if we label them with
05:41some isotopes like gallium 68
05:42we will get images but we can label
05:45with other allies like lutetium,
05:47in which case we can kill the cancer
05:50and what is up and coming and many
05:53prostate cancer patients are
05:54waiting for that eagerly is to get
05:57both imaging and treatment with
06:00prostate specific membrane antigen.
06:02It sounds like these
06:05technologies, if you're able
06:07to identify a specific antigen,
06:09a specific protein on a particular cancer,
06:14and target that with a particle that
06:17can kill it, it would seem to me
06:19that this would be a very specific
06:21way to kill cancer cells.
06:24You are correct. So in most cases
06:27our therapy has produced results that
06:30are comparable to other systemic
06:32therapy like chemotherapy but with
06:35substantially lower adverse effects.
06:37So we kind of achieve similar results
06:41but with less morbidity to our patients.
06:45Is this widely available or is
06:47this still in the research arena
06:49and undergoing clinical trials?
06:54As I mentioned before,
06:56we had iodine for treatment
06:59of thyroid cancer for decades,
07:02and more recently we have an already
07:05clinically approved drug,
07:07which is called Xofigo,
07:08which is actually labeled
07:10radioactive labeled radium,
07:11that can kill metastatic disease
07:13from prostate cancer in the bone,
07:16and most recently
07:17and obviously they've got a lot
07:19of press attention is lutera,
07:22which is again labeled
07:23dotatate that can kill
07:26advanced neuroendocrine tumors.
07:28And for those that are approved
07:32are those now taking over instead
07:36of being treated with chemotherapy,
07:38or are these now being treated
07:40with these theranostics?
07:45It's more like they're
07:48getting incorporated in the treatment
07:51algorithms, our patients might have heard
07:54there is something called the
07:57National Comprehensive Network which
07:59is a body that provides all these
08:01guidelines how the cancers are treated and
08:03slowly the radionuclide therapies are
08:06getting incorporated in those guidelines
08:09and are used when appropriate
08:12to treat advanced or metastatic cancer.
08:16Help me to understand
08:18that a bit better.
08:19I mean because on the one hand it
08:21sounds like this is so exciting, right?
08:23That these theranostics,
08:26if they can truly target
08:29these cancers and kill them,
08:32and they're specific enough in the
08:35sense that you know this is how
08:37we look for cancers on imaging,
08:40and so we know that
08:43they're very specific and don't have all
08:45of the side effects of chemotherapy.
08:48Why haven't they been widely adopted yet?
08:51What's the downside?
08:53Well, each cancer and each
08:56cancer stage is kind of different, so
09:00for example, in thyroid cancer it is
09:03generally given after a thyroidectomy,
09:08which is removal of the thyroid
09:10and after radioactive iodine
09:12is given most patients get cured,
09:15so thyroid cancer is a relatively
09:17well behaving cancer.
09:18So in this particular cancer we can actually
09:22achieve cure. In some other cancers,
09:24for example metastatic prostate cancer,
09:26when we are going to use
09:30radioactive isotopes we will have actually
09:32to prove that they have advantages
09:36versus other chemotherapy options,
09:39which requires large trials and
09:42I don't know if our patients have
09:44heard of different lines of chemotherapy,
09:46usually there is a first line and
09:48then if there is a progression
09:50second and third line and so on.
09:51So you not only have to prove
09:54that they generally work,
09:55but you have to find appropriate lines
09:57of the therapy for those tracers.
09:59So this is now in the
10:01process of active research.
10:03So basically they have in a way
10:06similar limitations as a chemotherapy,
10:09despite much lower side effects.
10:12If that cancer is very bad,
10:15like advanced castrate
10:17resistant prostate cancer,
10:19they will have less impact because
10:21the cancer is already so aggressive.
10:23But if thyroid cancer,
10:24for example,
10:26that cancer is relatively
10:27well behaving,
10:29then we actually can achieve cure.
10:31So basically,
10:32in the first situation we will
10:34buy time for the patients to
10:37give them longer survival.
10:38While in this version of thyroid
10:40cancer will actually achieve the cure.
10:43It sounds like there's
10:46still clinical trials ongoing
10:48to kind of evaluate the optimal
10:50situation in which these theranostics
10:52should be used. Is that right?
10:55Yeah, that's absolutely correct.
10:56So for the neuroendocrine tumors
10:59and prostate we'll actually be
11:00evaluating what are the optimal
11:02situations to be used. In the other cancer there
11:06are still not agents that
11:09are either approved clinically
11:11or approved for trials.
11:14There will be a so-called early
11:15phase one and phase two studies
11:17to see whether they work at all.
11:19So at the moment again, thyroid,
11:22prostate and NETs are where
11:25Radionuclide therapies
11:26have advanced the most.
11:28Are there other cancers
11:30that are on the horizon?
11:31Are there other advances that you're
11:34particularly excited about?
11:36I just laughed a little bit about
11:38this because we're getting so many
11:40contacts from the pharmaceutical
11:42companies there are almost tracers
11:44for every cancer that you can imagine,
11:47but they will have to pass through
11:49phase one and phase two trials to see
11:52which of these tracers would make
11:54sense to develop as clinical agents.
11:58And tell us a little bit more about the
12:00side effects of these theranostics because
12:03it sounds like with them being so targeted,
12:06granted you know it makes a
12:08difference how aggressive the cancer
12:10is and how far gone it is,
12:12but do they have a lot of side effects?
12:14Because it seems to me that when
12:17we talk on the show about chemotherapy,
12:20chemotherapy really targets many cells.
12:23Any rapidly dividing cell,
12:25which is why they cause
12:28things like hair loss and bone
12:30marrow suppression and so on,
12:32because these are rapidly dividing cells.
12:34But in the situation where
12:38a protein that is very specific to a
12:41cancer can be targeted and almost like
12:44a laser killed by these theranostics.
12:48One would imagine that the side
12:50effects are different,
12:52perhaps more local.
12:53Tell us about the side effects that
12:56patients who are undergoing therapies
12:58with these agents might face?
13:00That's a little bit surprising,
13:03but you have to remember before
13:06the tracer gets localized
13:08to the tissue of interest,
13:10it still stays for awhile in the blood and
13:13to some extent goes to the bone marrow.
13:16So unfortunately, even through the radio tracers,
13:19although we have less
13:21toxicity to the bone marrow,
13:23patient still can get bone marrow toxicity,
13:26which can drop their blood counts,
13:28although this is very,
13:30very less pronounced with
13:32radionuclide tracers than with the
13:34conventional chemotherapy and then
13:36other side effects are
13:38more dependent on how they
13:41are eliminated from the body.
13:43So for example,
13:44for NETs we worry about
13:47kidneys because that's where they
13:49accumulate a lot when we get they get
13:53eliminated or in let's say
13:56prostate cancer, we worry about
13:59GI tract because patients sometimes
14:01get GI side effects.
14:03So again, it's a degree of toxicity,
14:06but unfortunately pretty much
14:09every systemic treatment would,
14:11to some extent have a bone
14:12marrow side effect.
14:13Well we're going to take
14:16a short break for medical minute,
14:18and when we come back we'll talk a
14:20little bit more about some of your work
14:22looking at COVID-19 vaccine and its
14:25effect on PET scans. Please stay
14:27tuned to learn more with my guest
14:29Doctor Darko Pucar.
14:31Funding for Yale Cancer Answers
14:33comes from AstraZeneca, dedicated
14:35to advancing options and providing
14:37hope for people living with cancer.
14:40More information at AstraZeneca Dash us.com.
14:46The American Cancer Society estimates that
14:48over 200,000 cases of Melanoma will be
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14:53with over 1000 patients in Connecticut alone.
14:56While Melanoma accounts for only
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15:01it causes the most skin cancer deaths,
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15:37yalecancercenter.org. You're listening
15:39to Connecticut Public Radio.
15:42Welcome
15:42back to Yale Cancer Answers.
15:44This is doctor Anees Chagpar
15:45and I'm joined
15:47tonight by my guest Doctor
15:48Darko Pucar and we're talking
15:51about nuclear medicine and before
15:53the break we spent some time
15:55talking about the role that nuclear
15:58medicine plays both in diagnosis
16:00as well as potentially in the
16:02therapeutic management of cancer.
16:04But Doctor Pucar has
16:07done some interesting work
16:09looking at the impact of COVID-19
16:12Vaccine on PET scans.
16:14Darko, tell us a little bit
16:16more about that.
16:18Thank you for this question.
16:19This is actually something very
16:21exciting to myself and my team members
16:24because we kind of anticipated once
16:27the vaccine started rolling out that
16:29we're going to see some active lymph
16:33nodes at the site of vaccine injection.
16:36So if, let's say you would get
16:39injection in the left deltoid muscle,
16:41you are expected to get
16:43activity in the left armpit.
16:45We kinda knew that was going to
16:47happen because that was happening
16:49with influenza and since last fall
16:53influenza was given relatively rapidly
16:55because we are actually seeing
16:58for like a week or several weeks
17:02actually influenza active lymph nodes.
17:05So we were already prepared as soon as
17:09COVID vaccine rollout is expected to
17:12start collecting the data immediately.
17:14So we were collecting actually
17:16the data for all the patients that
17:19had a pet scan at Yale will first
17:21try to determine whether they had
17:23COVID vaccine or not,
17:25and then we'll assess whether
17:27they have active nodes or not.
17:29And in the beginning the collection
17:31was relatively easy because all
17:33the vaccines were administered at
17:35Yale so we could get a very precise
17:37understanding who had vaccine,
17:39who didn't and
17:41which type of the vaccine.
17:44So we have collected those data as
17:47quickly as possible and we published
17:50the JAMA article on 68
17:53patients that actually had vaccine,
17:55listing the frequency of positivity in
17:58Pfizer and Moderna vaccines,
18:01which is kind of useful to the
18:03practitioner as we'll discuss.
18:05So tell me more. What did
18:07you find and what happened?
18:09So basically the reason why we
18:12really wanted to know this is because
18:15these lymph nodes theoretically
18:17can mimic cancer, which would be
18:19like a false positive finding.
18:21Or they can mask cancer.
18:22If we think that these nodes from
18:25the vaccine but actually turn out
18:27to be nodes from the cancer.
18:30So in order to avoid the errors,
18:33we kind of need everyone to participate.
18:36Both the patients, the providers
18:39that are administering the vaccines,
18:41the oncologists and us in
18:43the nuclear medicine. So it
18:45is very important to know the date,
18:48the type and the dose and the
18:50site of vaccine administration.
18:53Also, it is very important to
18:56avoid administering the vaccine
18:59on the side where cancer might be.
19:02So, for example,
19:03if you have a right breast cancer,
19:05you shouldn't be getting vaccine
19:07in the right arm.
19:08You should be getting the vaccine
19:10in the left arm.
19:11Similarly for other cancers that
19:13will go to the axilla like Melanoma,
19:16for other cancers like lymphoma,
19:18it gets more complicated because
19:20they can go to different nodes,
19:24but it's important to see whether,
19:25for example, they had nodes
19:28in one versus the other armpit,
19:30to determine which arm,
19:32which side would be more safe
19:35to inject and for patients
19:37it is extremely important to tell
19:40their oncologist that they will be
19:43getting the vaccine if they have some
19:45of those cancers that I mentioned
19:47to tell the person who is giving
19:50the vaccine to avoid the side,
19:52which can be confusing.
19:54And when they get their PET questionnaire,
19:57which is like a survey that we
19:59administer prior to PET scan,
20:01and that's a good idea
20:03even if they didn't get the vaccine,
20:08they should ask to see the chart or in epic,
20:10but they should actually list if
20:12they have any acute symptoms.
20:15Especially something that
20:17looks like inflammation,
20:18and they also should provide information as to
20:21when did they get vaccine?
20:23What kind of vaccine,
20:24and in which side of the arm
20:27in left or the right?
20:31For example, our data have demonstrated that
20:33those reactive nodes that can either
20:36mimic or mask cancer and more commonly
20:39after second dose of the vaccine,
20:42then after the first dose of vaccine
20:44which you would kind of expect based
20:47on immunologic phenomenons
20:49that come with the vaccines.
20:50And we also found that they are a
20:52little bit more common with
20:54Moderna than with Pfizer vaccine.
20:56So how long does the
21:00effect last on the PET scan?
21:02So for example,
21:04let's say you got the vaccine today.
21:08How long after that would you
21:10anticipate that you would still
21:12be able to see those enlarged
21:15lymph nodes by pet after today?
21:18That's a great question. And actually,
21:20when we did our original article,
21:22we couldn't answer that question
21:24because we had relatively few patients.
21:27I cannot discuss
21:29too much because we have to finish
21:30the analysis, so I don't want to be giving
21:34statements ahead of the statistician,
21:36but based on our preliminary data
21:39now of several hundred patients,
21:41it seems that probably it would take
21:45at least several weeks
21:49for the vaccine effect to disappear,
21:53and it seems again,
21:54this is probably too early,
21:57the final word is that it lasts
22:00a little bit longer with Moderna than
22:01Pfizer.
22:04I think that some of the things that
22:06you're saying make intuitive sense, right?
22:09If you have a known right breast cancer
22:13or known right arm Melanoma there,
22:17getting an injection on that right
22:19side can certainly be confusing
22:21to a radiologist who's trying to
22:23interpret whether the lymph nodes
22:25look ugly because of the cancer
22:27or look ugly because of the vaccine.
22:30But the
22:31other point though,
22:33is that you may have gotten the
22:36shot without knowing that you also
22:38were going to develop a cancer
22:40and then find the cancer later,
22:43and so that's where things get a
22:47little bit tricky when one didn't
22:50know about the other diagnosis.
22:53That's absolutely right.
22:56However, most of the time when
22:59we do PET scans prior to actual
23:02diagnosis of cancer is for lung
23:06nodules and fortunately lung cancer
23:09very, very rarely goes to the armpit,
23:12so in that situation we'll know based on
23:16the expected distribution.
23:19It will be obviously more difficult
23:21if a patient eventually gets
23:24diagnosed with lymphoma.
23:26And then it could in some time
23:29there are unfortunately few cases
23:31that we couldn't really tell,
23:33but although it looks really ominous,
23:38it is a relatively small number of cases
23:41that after careful analysis that we
23:43cannot determine what's going on and
23:46those we'll have to closely follow up,
23:48obviously.
23:49So you know getting to the point of
23:52the people with lymphoma, for example,
23:55where you know it would be expected
23:57that you would have many enlarged lymph
23:59nodes trying to distinguish that versus
24:03response to a COVID
24:05vaccine must be pretty difficult.
24:07What kind of tools do you
24:09use as a nuclear medicine physician
24:11who interprets these scans to tell
24:13the difference one to the other?
24:16Or is this something that relies on a biopsy?
24:20I'm hoping that in most cases we
24:23really do not need the biopsy and
24:25we actually didn't comment on the result to
24:27biopsy
24:29because, for example,
24:31the activity after vaccine
24:35is usually not very, very high.
24:38So if patients have a disease like
24:41a diffuse large B cell lymphoma,
24:43those have very higher activity
24:45than it would be with the vaccine.
24:52The other thing is patients,
24:54for example,
24:55has disseminated disease.
24:58At that point, it may not be necessary
25:01to make a distinction for the axilla,
25:04because if they are in all
25:05other locations on the body,
25:07it won't change the management
25:09where I kind of see this could be
25:12really a problem if a patient has a
25:14so-called low grade lymphoma which
25:17do not have very high activity and
25:19we find isolated nodes in
25:24let's say bilateral axilla.
25:27So then it would be great,
25:30then we'll presume, I guess,
25:31in one axilla that is probably
25:33due to lymphoma,
25:35the one which is not injected.
25:36But the injected axilla
25:38probably won't know unless we
25:40as you said we do the biopsy
25:43and presumably you can tell
25:46the difference between enlarged
25:48lymph nodes that are due to benign
25:51conditions like sarcoid or other
25:53things versus the COVID vaccine on
25:56these PET scans. Is that right?
25:59In principle yes,
26:01because sarcoid would tend to be in the
26:06nodes around the heart industry.
26:09In the area that we call media Steinem.
26:11While the vaccine nodes
26:13would tend to be in armpit,
26:15although this differentiation
26:16again is not absolute.
26:19But since we still rarely image circulated,
26:24let's say independently from the cancer,
26:28that's way less common situation.
26:31That would happen really
26:33to be a diagnostic dilemma,
26:35and so now that we're kind of in the
26:39the scenario where you know people
26:41are now thinking about booster shots,
26:44do you think that that's going to
26:46cause even more of a conundrum?
26:48You saw that the lymph
26:51nodes were more reactive on pet after
26:54the second dose of the COVID vaccine.
26:58Do you think that's going to be
26:59the case after the third dose?
27:02Well, that's a very interesting question
27:04so far I have seen only two cases
27:07after the booster and one was active.
27:10The other was not active,
27:11but I didn't have dilemma because based on
27:13the other characteristics or cancers
27:16and knowing where the vaccine was,
27:18I was able to confidently say.
27:20But I would also want to bring
27:23another interesting point which we
27:24are actually going to investigate.
27:28We can view those nodes after
27:31vaccine as negative because it can
27:34create a diagnostic confusion,
27:36but we are also hoping to investigate
27:39whether activity of these nodes actually
27:41can predict the efficacy of the vaccines.
27:45And this is for example,
27:49there is an Israeli study
27:52and they showed that
27:54the activity in the nodes
27:56correlate with the level of anti
27:59spike which is that protein that is
28:02very important in COVID antibodies.
28:04So basically there was a correlation
28:07between activity in these nodes
28:10and antibody levels which in a way
28:13would reflect the potential level of
28:16protection that people would have.
28:18So maybe in the future we can not
28:21only be threatened by this phenomena,
28:24but maybe we can
28:25even use iy to predict what level of
28:28immunity cancer patients would achieve.
28:31Doctor Darko Pucar is an associate
28:33professor of radiology and biomedical
28:35imaging at the Yale School of Medicine.
28:38If you have questions,
28:39the addresses cancer answers at
28:41yale.edu and past editions of the
28:44program are available in audio and
28:46written form at Yale Cancer Center Org.
28:48We hope you'll join us next week to
28:50learn more about the fight against
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