1. PET SCAN IN ONCOLOGY
DR. ARNAB BOSE
Dept. of Radiotherapy
NRS Medical College, Kolkata
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2.  Imaging often is the best means of noninvasively
identifying and assessing tumors. With information
gleaned from imaging studies, the prognosis can be
established and treatment decisions made with greater
certainty.
 Broadly stated, cancer imaging can be performed
using anatomic or functional imaging methods.
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3.  The traditional imaging of the patient with cancer,
and the most established methods, are based on
anatomic imaging.
 However, interest is increasing in more functional
methods in cancer imaging.
 Further, several anatomic imaging methods offer
functional components that complement the anatomic method.
 Hybrid images, derived from and displaying both
functional and anatomic data, also are becoming more widely
available, often coming from the same hybrid imaging machine.
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4.  Anatomic imaging normally detects a phenotypic alteration
that is sometimes, but not invariably, associated with cancer—
a mass. However, with anatomic imaging, we often do not
know whether masses are the result of malignant or benign
etiologies, as in solitary pulmonary nodules or borderline-size
lymph nodes.
 Similarly, small cancers are undetectable with traditional
anatomic methods, because they have not yet formed a mass.
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5.  After surgery, it is even more difficult to assess for the
presence of recurrent tumor with anatomic methods.
 Post-treatment scans are complicated by the need for
comparisons with normal anatomy to detect altered
morphologic findings as a result of cancer.
 Anatomic methods do not predict the response to treatment
and do not quickly document tumors responding to therapy.
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6.  Positron Emission Tomography ( P E T ), a functional
imaging method, helps to address many of the limitations of
anatomic imaging, and
when combined with anatomic images in fusion images,
is emerging as a particularly valuable tool, providing both
anatomic precision and functional information in a single image
set.
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7.  PET provides information on the metabolic function of
organs or tissues by detecting how cells process certain
compounds such as glucose. Most cancer cells metabolize
glucose at a much higher rate than normal tissues. By
detecting increased radio-labelled glucose metabolism with a
high degree of sensitivity, PET identifies cancerous cells, even
at an early stage, when other imaging modalities may miss
them.
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8.  In a typical PET study, one administers a positron emitting
radionuclide by intravenous injection. The radionuclide
circulates through the bloodstream to reach a particular organ.
 The positrons emitted by the radionuclide travels a distance
of a few millimeters in tissue before it collides with a
negatively charged electron. This collision annihilates the
entire mass of the positron and electron, generating two
photons with energy of 511 KeV each.
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9.  These two photons travel at the speed of light in exactly
opposite directions (i.e.180 degrees apart).
 Coincident detection of these two photons by two oppositely
positioned detectors in the PET scanner results in images with
a much higher resolution compared with the conventional,
single-photon nuclear medicine studies and produces the
possibility of quantitative measurement of the tracer uptake in a
volume of interest.
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10. detector array
 PET machines are composed of a ring of
detectors within which the patient is
gamma photon
positioned .
positron  The gamma photons emitted
travel at the speed of light. Rather than
radiotracer register the gamma photons as two
separate events, the PET machine registers
them as a paired event.
 It does this through the establishment
of time windows. If two gamma photons
are detected within the same (small) time
window, the camera records them as
coming from the same annihilation event.
As the gamma photons travel at 180 o to
each other, the camera draws a line of flight
between the two events and determines
that the annihilation must have occurred
along this line.
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11.  The PET machine generates transverse images depicting
the distribution of positron emitting radionuclides in the patient
and uses annihilation coincidence detection to obtain
projections of the activity distribution. The transverse images
are obtained through the process of filtered back-projection.
 Detectors used for coincidence detection in modern PET
machines are scintillators made of bismuth germanate (BGO)
or lutetium oxyorthosilicate doped with cerium (LSO:Ce)
that transform the 0.511 MeV gamma ray energy into visible
photons detected by photomultiplier tubes (PMTs).
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12.  The radionuclides used in PET studies are produced by
bombardment of an appropriate stable nuclide with protons
from a cyclotron, thereby producing positron emitting
radionuclides that are subsequently attached to clinically
useful biological markers.
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13.  The 18F radionuclide attached to the
2-fluoro-2-deoxy-D-glucose (FDG) molecule is the biological
marker most commonly used in studies involving glucose
metabolism in cancer diagnosis and treatment
(2-[18F] fluoro-2-deoxy-d-glucose).
 Tumor imaging with FDG is based on the principle of
increased glucose metabolism of cancer cells.
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14.  Like glucose, FDG is taken up by the cancer cells through
facilitative glucose transporters (GLUTs).
 Once in the cell, glucose or FDG is phosphorylated
by hexokinase to glucose-6-phospate or FDG-6-phosphate,
respectively.
 Expression of GLUTs and hexokinase, as well as the affinity
of hexokinase for phosphorylation of glucose or FDG, is
generally higher in cancer cells than in normal cells.
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15.  Glucose-6-phosphate travels farther down the glycolytic or
oxidative pathways to be metabolized, in contrast to FDG-6-
phosphate, which cannot be metabolized.
 In normal cells,glucose-6-phosphate or FDG-6-phosphate
can be dephosphorylated and exit the cells. In cancer cells,
however, expression of glucose-6-phosphatase is usually
significantly decreased, and glucose-6-phosphate or FDG-6-
phosphate therefore can become only minimally
dephosphorylated and remains in large part within the cell.
 Because FDG-6-phosphate cannot be metabolized, it is
trapped in the cancer cell as a polar metabolite, and it
constitutes the basis for tumor visualization on PET.
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16. NORMAL TUMOR
Over expression of Glucose transporters
Higher levels of Hexokinase
Down-regulation of Glucose-6-phosphatase
Anaerobic glycolysis, less ATP per glucose molecule,
more glucose molecules needed for ATP production
General increase in metabolism from high growth rates
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17.  A potential range of clinical scenarios in oncology for which
18F-FDG-PET has shown to be worthwhile includes:
i) The non-invasive characterization of the likelihood of
malignancy of mass lesions, which are not readily amenable to
biopsy, or for which biopsy attempts have already failed.
ii) The detection of cancer in patients at significantly increased
risk of malignancy on basis of elevated tumor markers, clinical
symptoms or signs but in whom routine tests have failed to
detect a cancer.
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18. iii) Staging of high-risk malignancy amenable to potentially
curative therapy for which disease extent is critical to treatment
selection.
iv) Planning of highly targeted therapy where delineation of
disease is critical to efficient and safe treatment delivery and
thereby, therapeutic success.
v) Assessment of therapeutic response in diseases with a
significant likelihood of treatment failure, and for which earlier
demonstration of therapeutic failure may benefit the patient.
vi) Surveillance of high-risk malignancies or evaluation at
clinical relapse where salvage therapies exist and for which
early intervention may be curative or prolong life.
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19.  It is important to recognize that, being a tracer of glucose
metabolism, 18F-FDG is not a ‘specific’ radiotracer for imaging
malignant disease.
 There are several benign conditions and many physiological
processes that lead to increased uptake of this tracer.
 These include, but are not limited to,
normal wound healing,
infection and inflammation,
active muscle contraction during the uptake period, and
activated brown fat.
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20.  Normal organs, including the brain, liver, kidneys and bone
marrow have relatively high 18F-FDG uptake, even under
fasting conditions, and this provides background activity that
may mask small lesions or malignancies with low glucose
metabolism.
 Such malignancies include some neuroendocrine tumors,
mucinous tumors, differentiated teratomas, many prostate
carcinomas, lobular breast cancer, some renal and
hepatocellular carcinomas, and
most bronchioloalveolar carcinomas.
 The relatively poor 18F-FDG uptake of these tumors
compromises the sensitivity of PET for the detection of tumor
sites.
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21.  The standardized uptake value (SUV) is a semi-quantitative
measure of the tracer uptake in a region of interest that
normalizes the lesion activity to the injected dose and body
weight; SUV does not have a unit.
 Despite initial enthusiasm, it is generally accepted that SUV
should not be used to differentiate malignant from benign
processes, and that the visual interpretation of PET studies by
an experienced reader provides the highest accuracy.
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22.  There are many factors influencing the calculation of SUV,
such as the body weight and composition, the time between
tracer injection and image acquisition, the spatial resolution of
the PET scanner, and the image reconstruction algorithm.
 Nonetheless, SUV may be useful as a measure to follow the
metabolic activity of a tumor over time within the same patient
and to compare different subjects within a research study under
defined conditions. For example, the SUV of an individual
tumor can be measured before and at different time points after
therapy, and any change can be used as an index of
therapeutic response.
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23.  Research in PET radiochemistry has provided access to
many alternative tracers for oncology at the present time.
 Many of these tracers have been evaluated in both
pre clinical and clinical studies.
 Some have the ability to uniquely characterize specific
aspects of tumour biology and, as a result, to offer several
diagnostic advantages in comparison with 18F-FDG in
particular types of tumours.
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24. 24

25.  Sensitivity describes how often the imaging test would
give a “positive result” in a patient with cancer (i.e., true-
positive [TP] finding). A test with high sensitivity has a low
number of false-negative results.
 Specificity is the frequency with which a test result is
negative if no disease is present, or the true-negative (TN)
ratio. A highly specific test has a low frequency of false-
positive results
 Accuracy is 100 * (TP + TN)/(TP + FP + TN + FN).
A highly accurate test is one with a low prevalence of
false-positive and false-negative results.
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26. PET Scan in Lung Cancer
 PET has an overall sensitivity of more than 90% and a
specificity of about 85% for diagnosing malignancy in primary
and metastatic lung lesions; the sensitivity of PET for
bronchoalveolar lung cancer and carcinoid of the lung is about
60%, and the specificity of PET for lung cancer is lower in
areas with a high prevalence of granulomatous lung disease.
 It is expected that the use of PET for diagnosing malignancy
in indeterminate lung nodules will continue to grow as more
patients are diagnosed with nodules on CT performed for other
indications or as a screening test.
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27.  FDG-PET is useful in staging of lung cancer by detecting
mediastinal nodal involvement PET has greater sensitivity and
specificity than CT, but it is still imperfect. Nodes that appear
involved by PET or CT should be sampled for confirmation of
their status when such information will lead to alterations in
clinical management, particularly when deciding whether to
consider resection.
 FDG-PET has also been studied for evaluating the response
to pre-operative chemotherapy or chemo-radiation and for
distinguishing between viable tumor and fibrosis in patients
who have received RT or chemotherapy, or both, in assessing
local disease control in patients treated non-operatively.
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28.  PET is justified instead of a battery of other tests (e.g., bone
scan, CT, MRI) to assess for distant metastases.
 PET is more sensitive (90% vs. 80%) and more specific
(90% vs. 70%) than bone scan in detecting bone metastases
from NSCLC; PET has a sensitivity and specificity of greater
than 90% in detecting adrenal metastases from NSCLC. Brain
CT or MRI is still needed because PET cannot reliably detect
brain metastases because of physiologically intense brain
uptake of FDG.
 For patients with stage IV tumors, PET may be able to
indicate the most accessible site for biopsy.
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29.  PET is also useful in restaging NSCLC.
In particular, PET appears to be more sensitive than CT in
differentiating post-irradiation change from local recurrence,
although differentiating these two entities remains a challenge.
The post-irradiation change in the chest can remain intense on
PET for up to several years. In differentiating local recurrence
from post-irradiation change, the intensity of uptake and its
shape should be taken into account
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30. PET Scan in Lymphoma
 Positron emission tomography (especially fused PET/CT) is
superior to conventional CT in staging of Hodgkin’s disease
and non-Hodgkin’s lymphoma; however, there is no definite
evidence that PET changes the initial management of
lymphoma patients. Nonetheless, because most recurrences
occur at the sites of the primary disease, pre-treatment PET
appears helpful in identifying recurrence.
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31.  Hodgkin’s disease and high-grade NHL are mostly markedly
avid for FDG and almost always visible on PET, whereas low-
grade NHL can be only mildly intense and, in rare cases,
completely invisible on PET.
 Intense spleen uptake (i.e., more intense than the liver)
before chemotherapy is a reliable indicator of its involvement,
but spleen involvement by lymphoma cannot be excluded with
normal uptake.
 PET cannot be used to reliably evaluate bone marrow
involvement.
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32.  The most promising role of PET in lymphoma management
appears to be in therapy monitoring: early prediction of
response to chemotherapy (i.e., interim or midway PET) and
evaluation of a residual mass for active lymphoma at the
completion of chemotherapy (i.e., end-of-treatment PET).
 The decrease of uptake associated with effective
chemotherapy seen on interim PET precedes the anatomic
changes seen on CT by weeks to months. Overall, metabolic
changes on interim PET after one or a few cycles of
chemotherapy are reliable predictors of response, progression-
free survival rates, and overall survival rates.
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33.  End-of-treatment PET has proven impact in patient care.
At the completion of chemotherapy, CT demonstrates a
residual mass at the initial site of disease in as many as 50%
of patients. On the end-of-treatment PET, these patients
demonstrate increased FDG uptake in the area of residual
lymphoma in contrast to those without active lymphoma. The
positive predictive value of residual uptake at the completion of
chemotherapy is more than 90%.
 In follow-up of patients in remission, PET is more sensitive
than CT in detecting recurrent disease.
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34. PET Scan in Head & Neck Cancers
 In initial staging of head and neck tumors, PET has a
sensitivity and specificity of about 90% for nodal staging, and
PET therefore is more sensitive and specific than CT or MRI. A
weakness of PET is its low sensitivity (30%) for nodal disease
in patients with disease in the neck at clinical stage N0.
 In addition to local staging, PET can detect synchronous
cancers and distant metastases. In initial staging of head and
neck cancers, a PET scan is overall most helpful in patients
with locally advanced disease because these patients have a
risk of 10% or greater for distant disease.
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35.  For restaging of head and neck tumors after radiation
therapy, PET is highly sensitive; however, the optimal time to
perform PET is a matter of debate.
There is a higher likelihood of false-positive findings when PET
is performed earlier than 3 months after irradiation.
 For patients presenting with metastatic neck nodes with
unknown primary PET is useful in the search for the original
lesion.
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36. PET Scan in Colorectal Cancers
 PET is highly sensitive in detecting distant hepatic
and extra-hepatic metastases.
 Considering the higher sensitivity of PET in detecting
distant metastases and the introduction of intravenous
contrast media to the CT portion of fused PET/CT, it is
conceivable that PET/CT will be increasingly employed in
pre-operative staging of colorectal cancer; the contrast-
enhanced CT portion of PET/CT can be used instead of
conventional CT or MRI for evaluation of anatomic resectability
of liver metastases.
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37.  PET plays an important role in restaging of colorectal
cancer and is even more important now that it is known that
treatment of limited metastatic disease can be curative.
 PET can visualize the site of the local and distant disease
when recurrence is suspected based on the clinical findings,
findings on other imaging modalities, or an increasing
CEA level with sensitivity and specificity higher than 90%
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38. PET Scan in Breast Cancer
 PET can increase the detectability of small primary breast
cancers and may be especially useful in evaluating patients
with dense breast tissue. Its role in routine patient care is
under investigation.
 In evaluating the axillary lymph nodes, PET does not play
any role because of its low sensitivity (60%) despite relatively
high specificity (80%). In contrast, PET is relatively sensitive
(85%) and specific (90%), and it is superior to CT (sensitivity of
54%, specificity of 85%) in evaluation of the internal mammary
chain lymph node for metastases.
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39.  The main role of PET in breast cancer lies in the
investigation of distant metastases and response monitoring.
 Compared with CT, PET has a higher sensitivity (90% vs.
40%) but lower specificity (80% vs. 95%) in detecting
metastatic disease.
 Overall, PET has the same sensitivity as bone scan in
detecting bone metastases (both about 90%), but PET appears
to be somewhat more sensitive than bone scan for osteolytic
lesions and somewhat less sensitive than bone scan for
osteoblastic lesions. PET has a higher specificity than bone
scan in detecting bone metastases (95% vs. 80%).
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40.  In patients with advanced breast cancer undergoing
neo-adjuvant chemotherapy, PET may differentiate responders
from non-responders as soon as the first cycle of therapy has
been completed. This may help improve patient management
by avoiding ineffective chemotherapy and supporting the
decision to continue dose-intensive pre-operative
chemotherapy in responding patients.
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41. In esophageal and gastric cancers, PET is useful to assess for
distant disease. PET is routinely used in the staging of
esophageal cancer, and it has the potential to be used for
monitoring the effect of neo-adjuvant therapy.
In ovarian, uterine, and cervical cancers, PET is used to assess
for recurrent disease. In cervical cancer, PET plays an
important role in nodal staging and can have a role in
radiotherapy planning.
In malignant melanoma, PET is used to evaluate the presence
of distant metastases. In sarcoma, the most intense areas on
PET have usually the highest grade and should be considered
in planning the biopsy.
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42. This is a very interesting case
of a 67 year old gentleman with three
pulmonary nodules on CT scan. He
was referred for PET/CT, which
showed only one of the three nodules
was FDG avid.
A subsequent biopsy of the FDG avid
nodule showed adenocarcinoma.
The surgeon and the patient decided
to resect all three nodules. The
pathology of the three nodules
showed adenocarcinoma, a more
peripheral area of infarct from
tumor embolus and in the other
lung a benign hamartoma.
In this particular case, PET/CT
accurately identified the malignant
nodule from the other two benign
nodules.
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43. thank you
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