NUCLEAR MEDICINE

FOR MEDICAL STUDENTS

2022-2023
Alexandru Naum, MD, PhD
What is Nuclear Medicine ?
What is Nuclear Medicine ?
• A discipline of medicine using radio-isotopes for diagnosis and
treatment of diseases.
• Nuclear medicine imaging uses small amounts of radioactive materials
called radiotracers that are typically injected into the bloodstream,
inhaled or swallowed.
• The radiotracer travels through the area being examined and gives off
energy in the form of gamma rays which are detected by a special
camera and a computer to create images of the inside of your body.
• Nuclear medicine imaging provides unique information that often
cannot be obtained using other imaging procedures and offers the
potential to identify disease in its earliest stages.
Nuclear Medicine

Medical specialty where unsealed sources of radioactivity are

administered in the form of radiopharmaceuticals are used for
diagnostic and therapeutic purposes

Radioactive dose Patient Detection Image

History
• Nuclear medicine is associated with a long history, to which
scientists from various different fields such as physics, medicine
chemistry and engineering have contributed over the decades.
• This multidisciplinary involvement means it has been difficult
for historians to determine the origins of nuclear medicine.
• However, researchers believe the birth of this medical speciality
probably occurred somewhere between 1934 when artificial
radioactivity was first discovered and 1946 when radionuclides
were first produced for medical use by the Oak Ridge National
Laboratory.
ANTOINE HENRI BECQUEREL PIERRE CURIE MARIE CURIE GEORGE DE HEVESY
1852 – 1908 1859 – 1906 1867 – 1934 1885-1966
The Nobel Prize in Physics 1903: "in The Nobel Prize in Physics 1903: "in The Nobel Prize in Physics 1903. The Nobel Prize in Chemistry 1943.
recognition of the extraordinary services recognition of the extraordinary The Nobel Prize in Chemistry 1911: "in Prize motivation: "for his work on
he has rendered by his discovery of services they have rendered by their recognition of her services to the the use of isotopes as tracers in the
spontaneous radioactivity" joint researches on the radiation advancement of chemistry by the study of chemical processes"
phenomena discovered by Professor discovery of the elements radium and
Henri Becquerel" polonium, by the isolation of radium and
the study of the nature and compounds of
this remarkable element"
ERNEST ORLANDO LAWRENCE HAL OSCAR ANGER HERRMAN LUDWIG BLUMGART
1901 –1958 1920 – 2005 1895-1977
The Nobel Prize in Physics 1939: "for the In 1957, he invented the scintillation camera, known also American physician, cardiologist and
invention and development of the cyclotron as the gamma camera or Anger camera. pioneer of diagnostic nuclear medicine. In
and for results obtained with it, especially 1925, Hermann Blumgart performed the
with regard to artificial radioactive first diagnostic procedure using radioactive
elements" indicators on humans. Referred to as the
father of diagnostic nuclear medicine, in
that he performed the first radiotracer test
on a human (himself).
Nuclear Medicine Evolution

2D small region scan–thyroid

2D whole-body scan–bone

3D dynamic scan–heart

3D whole-body fusion scan

Radioisotopes
Radioactivity
Radiopharmaceutics
Radioisotopes, Radioactivity
• Isotopes of an atom have the same number of protons,
but a different number of neutrons.

• Radioisotopes, Radionuclides: unstable isotopes which

are distinguishable by radioactive transformation.

• Radioactivity: the process in which an unstable isotope

undergoes changes until a stable state is reached and in
the transformation emits energy in the form of radiation
(alpha particles, beta particles and gamma rays).
Radioactivity

1- Natural radioactivity:
Nuclear reactions occur spontaneously

2- Artificial radioactivity:
The property of radioactivity produced by particle bombardment or
electromagnetic irradiation.
A- Charged-particle reactions
e.g. protons (1 1H)
e.g. deuterons ( 2 1H)
e.g. alpha particles (4He)
Radiation
• Radiation refers to particles or waves coming from the nucleus of the
atom (radioisotope or radionuclide) through which the atom attempts
to attain a more stable configuration.
 Mode of radioactive decay:

• Radioactive decay is the process in which an unstable atomic nucleus

spontaneously loses energy by emitting ionizing particles and radiation.

• This decay, or loss of energy, results in an atom of one type, called the
parent nuclide transforming to an atom of a different type, named the
daughter nuclide.
Properties of an Ideal Diagnostic
Radioisotope:
• Types of Emission:
– Pure Gamma Emitter: (Alpha & Beta Particles are unimageable & Deliver High
Radiation Dose.)

• Energy of Gamma Rays:

– Ideal: 100-250 keV e.g.
– Suboptimal:<100 keV e.g.
>250 keV e.g.

• Photon Abundance:
– Should be high to minimize imaging time
Properties of an Ideal Diagnostic Radioisotope:

• Example: For a Bone Scan which is a 4-h procedure, 99mTc- phosphate compounds
with an effective half-life of 6 h are the ideal radiopharmaceuticals

• Patient Safety:
– Should exhibit no toxicity to the patient.

• Preparation and Quality Control:

– Should be simple with little manipulation.
– No complicated equipment
– No time consuming steps
Radiation measurement:
The basic unit for quantifying radioactivity (i.e. describes the rate at which
the nuclei decay).

Curie (Ci):
• Curie (Ci), named for the famed scientist Marie Curie
Curie = 3.7 x 1010 atoms disintegrate per second (dps)
Millicurie (mCi) = 3.7 x 107 dps
Microcurie (uCi) = 3.7 x 104 dps

Becquerel (Bq):

A unit of radioactivity. One becquerel is equal to 1 disintegration per second.

Gamma ray:

• Useful gamma sources include Technetium-99m, which is used as a

"tracer" in medicine.

• This is a combined beta and gamma source, and is chosen because

betas are less harmful to the patient than alphas (less ionisation) and
because Technetium has a short half-life (just over 6 hours), so it
decays away quickly and reduces the dose to the patient.
99Mo/99mTc Generator:
• Parent: 99Mo as molybdate
• Half-life: 66 hr.
• Decays by - emission, gamma: 740, 780 keV.
• High affinity to alumina
• Daughter: 99mTc
• Adsorbent Material: Alumina (aluminum oxide)
• Eluent: saline (0.9% NaCl)
• Eluate: as pertechnetate
𝟗𝟗 𝑴 𝒐 − 𝟗 𝟗 𝑻𝒄 𝒎 generator
99𝑇𝑐𝑚 most common radioisotope used in nuclear medicine:
99
Mo 99m
Tc 99𝑇𝑐 + 140 keV 𝛾
𝐻𝑎𝑙𝑓−𝑙𝑖𝑓𝑒=66 ℎ 𝐻𝑎𝑙𝑓−𝑙𝑖𝑓𝑒=6.02 ℎ

• Also called a Molly or Cow

• Typically used for one week
• 99 𝑀𝑜 bound to alumina column
• Chemically different → not bound to
column → eluted from column with
5÷25 ml saline
• 75÷85% of available 99𝑇𝑐𝑚 extracted
Properties of an Ideal Diagnostic Radioisotope:

• Easy Availability:
o Readily Available, Easily Produced & Inexpensive:
• Target to Non target Ratio:
o It should be high to:
 maximize the efficacy of diagnosis
 minimize the radiation dose to the patient
• Effective Half-life:
o It should be short enough to minimize the radiation dose to patients and long
enough to perform the procedure. Ideally 1.5 times the duration of the
diagnostic procedure.
Application of radiopharmaceuticals:
1- Treatment of disease: (therapeutic radiopharmaceuticals)
They are radiolabeled molecules designed to deliver therapeutic doses
of ionizing radiation to specific diseased sites.
• Chromic phosphate P32 for lung, ovarian, uterine, and prostate
cancers
• Sodium iodide I 131 for thyroid cancer
• Samarium Sm 153 for cancerous bone tissue
• Sodium phosphate P 32 for cancerous bone tissue and other types of
cancers
• Strontium chloride Sr 89 for cancerous bone tissue
Application of radiopharmaceuticals:
2- As an aid in the diagnosis of disease (Diagnostic Radiopharmaceuticals)
The radiopharmaceutical accumulated in an organ of interest emit gamma radiation which are
used for imaging of the organs with the help of an external imaging device called gamma
camera.

- Radiopharmaceuticals used in tracer techniques for measuring physiological parameters (e.g.

51
Cr-EDTA for measuring glomerular filtration rate).

- Radiopharmaceuticals for diagnostic imaging

(e.g.99m TC-methylene diphosphonate (MDP) used in bone scanning).

Common radiotracers for Conventional Nuclear Imaging
Radiotracer 𝑬𝜸 (keV)
Myocardial perfusion (rest/stress)
201𝑇𝑙
68÷80
99 𝑇𝑐𝑚-Sestamibi 140
99 𝑇𝑐𝑚-Tetrofosmin 140
Cerebral perfusion
99 𝑇𝑐𝑚-HMPAO 140
99 𝑇𝑐 𝑚 -ECD 140
Oncology
67𝐺𝑎 93, 185, 300
201𝑇𝑙
68÷80
99 𝑇𝑐𝑚-Sestamibi 140
Somastatin receptors: 99𝑇𝑐𝑚-Depreotide, 111 𝐼𝑛-Octreotide 140 99 𝑇𝑐 𝑚 , 171, 245 111𝐼n
Labelled antibodies, peptides
 Common radiotracers for PET
Radionuclide Half-life (min) 𝜷+ fraction Max . kinetic Average 𝜷+ Clinical
energy (Mev) range in water application
Radiotracer (mm)

11𝐶
20.4 0.99 0.96 1.0 Cardiac
11𝐶-palmitate metabolism
13𝑁
9.96 1.00 1.19 2.0 Cardiac blood
13𝑁𝐻 flow
3
15𝑂
2.07 1.00 1.72 2.0 Cerebral blood
𝐻2 15𝑂 flow
18𝐹
109.7 0.97 0.64 0.6 Oncology,
18𝐹𝐷𝐺 inflammation,
cardiac viability
82𝑅𝑏 1
1.27 0.95 3.35 2.8 Cardiac
82𝑅𝑏𝐶𝑙
2
perfusion
Nuclear Medicine Imaging
Devices
Nuclear Medicine Imaging Devices
Medical specialty where unsealed sources of radioactivity are
administered in the form of radiopharmaceuticals are used for
diagnostic and therapeutic purposes

Radioactive dose Patient Detection Image

Major imaging systems categories
• Gamma camera systems
 Planar gamma cameras (2-D images)
 Single photon emission computed tomographic (SPECT) systems (3D
images)
• Positron emission tomography systems
 PET (Tomographic systems 3D images)
• Multimodality systems
 SPECT-CT
 PET-CT
 PET-MRI
The Gamma Camera
• Gamma camera= instrumental basis for:
 SPECT
 Planar scintigraphy
 used in nuclear medicine imaging = emission imaging = radioactive
source inside patient’s body
 In both SPECT and planar scintigraphy radiation source used =
mainly 99𝑇𝑐𝑚 → 140 keV 𝛾-rays → hence the name gamma camera
• Patient lies beneath gamma camera positioned close to
organ of interest
 Gamma camera components and operation
• Gamma camera components:
• Collimator
• Scintillator
• Array of PMTs
• ‘Anger’ position network
• Pulse height analyser (PHA)
• Digitizer = ADCs
• Computer to build up the image from
many detection events
• Operation:
• 𝛾-rays from patient travelling in certain
directions selected
• 𝛾-rays produce scintillation
• Scintillation detected by PMTs
Gamma camera operation
• Detects 𝛾-rays and for each 𝛾-ray records:
 X-Y position
 Energy
 Time → can be linked to other information (for ex. ECG)
• Main features:
 Capable of withstanding 𝛾-ray detection rates up to tens to
thousands events per second
 Reject 𝛾-rays scattered in the body → no useful spatial information
 As high sensitivity as possible → high quality images within
clinically acceptable imaging time.
 Single Photon Emission Computed Tomography (SPECT)

• Basic principle:
– Source:
1. Radioisotope usually emitting a single 𝛾-ray per nuclear disintegration →
from where ‘Single Photon’
2. Radiotracer injected in patient → 𝛾-rays are emitted from inside the
body → from where ‘Emission’
– Provides 3D images using CT techniques:
1. System rotates around patient → detects 𝛾-rays at different angles → 2D
projections
2. Tomographic reconstruction algorithm applied to 2D projections → 3D
images
 SPECT Scanner Components
1. Two or three gamma
cameras = heads
=multi- headed systems
→ acquire multiple
views simultaneously

2. Moving bed often

attached → allows
whole body studies
𝟑𝟔𝟎° rotation orbits
Circular orbit Contoured orbit

• Higher spatial resolution

• Needs complex path for detector head
SPECT Imaging
Positron Emission Tomography (PET) systems
• Tomographic technique that uses radiotracers
administered to the patient → emission imaging
• Basic principle:
1. Radiotracers used undergo 𝛽+ decay → emit e+
2. e+ travels on average 0.1÷3 mm in tissue depending on
radiotracer → scatters → loses energy → comes to rest
3. e+ at rest combines with atomic e− to form positronium
4. Positronium decays emitting two back-to-back 511 keV
• 𝛾-rays
𝜷+ decay
Example
• Proton-rich or neutron
𝛽+
deficient radionuclide ejects 15
8 𝑂 decay
15
7𝑁 + 𝛽+ + 𝜈 + 𝐸
𝛽+-particle = e+ = +1 charge 𝐸 = shared randomly between 𝑣 and
in the process: kinetic energy of 𝛽+
𝑝 → 𝑛 + e+ + 𝜈 Average kinetic energy 𝐸𝛽 + ≅
𝛽+
• 𝑍 → 𝑍 − 1, 𝐴 and atomic 𝐸 𝑚 𝑎 𝑥 /3
weight remain the same 15
8𝑂
1.022 MeV
𝛽+ decay

𝐸 𝑚+𝑎 𝑥 = 1.7 MeV

𝛽

15
7𝑁
PET components
• Detection unit = full ring of scintillating detectors
surrounding the patient
• Scintillation read-out chain:
– PMTs → convert light into electric signal
– Pulse height analyzer
• Annihilation coincidence detection unit
 Annihilation coincidence detection
• Time
– 1st 𝛾-ray detected at time 𝑡1 = 0
– 2nd 𝛾-ray detected at time 𝑡2
• Position
– 1st 𝛾-ray detected assigned to crystal 1
– 2nd 𝛾-ray detected assigned to crystal 2
• Coincidence
– If 𝑡2 falls into time window → 2nd 𝛾-ray assigned to same annihilation
– If crystals 1 and 2 are operated in coincidence → two 𝛾-rays
→ accepted as ‘true event’ and LOR drawn
Scintillating detector ring
• Large number of small scintillation crystals
placed in circular ring surrounding patient
with diameter:
– 70 or 85 cm for abdominal scanner
– ~45 cm for head scanner
• Up to 48 multiple rings staked axially
with retractable lead collimation septa in
between → head/foot FOV = ~16 cm
• Ideal geometry = one crystal coupled to one
PMT → better spatial resolution but too
expensive
• Geometry = ‘block detector’ design
Scintillation crystals
• Ideal scintillation material for use in PET has:
1. High detection efficiency for 511 keV 𝛾-rays
2. Short decay time to allow for short coincidence resolving
time
3. High light yield to reduce the complexity and cost of the system
4. Emission wavelength near 400 nm that corresponds to maximum
sensitivity for standard PMTs
5. Optical transparency at emission wavelength to minimise
reabsorption
6. Index of refraction close to 1.5 to ensure efficient light
transmission between crystal and PMT
Annihilation coincidence detection unit
• Time
– Fixed ‘coincidence resolving time’
= time window for each PET
system
– Each signal recorded in a crystal
given a time-stamp with precision
1÷2 ns to account for different
arrival time of two 𝛾-rays at
detector ring
• Position
– Geometric ‘coincidence arcs’
• = two arcs at 180° formed by
• set number of crystals
Types of coincidence events in PET

True
Both 𝛾-rays escape without
scatter and interact in detectors

Random (accidental)
Scatter Two 𝛾-rays from
One or both 𝛾-rays separate emissions
scatter in tissue strike the detectors at
the same time
Hybrid Modality Technologies
SPECT/CT
• SPECT/CT scanner. There is a dual head
gamma camera located in front of the CT
scanner gantry and bore.
• The gamma camera portion has the same
characteristics as the SPECT cameras just
discussed.
• A SPECT/CT system has several advantages,
• accurately co-registered SPECT
• anatomic CT images as well as data-rich
attenuation correction using CT transmission
images.
• CT attenuation correction allows for better
quantification of radiotracer uptake than with
other methods. The incorporated CT scanners
are typically less expensive versions of
standard multidetector helical CT scanners.
PET-CT
• Stand-alone PET scanner
almost entirely replaced by
hybrid PET/CT scanners:
1. Two separate systems one next
to the other
2. Bed that slides between two
systems
• Rationale:
– Improved attenuation
• correction
– Ability to fuse anatomical
(morphological) and functional
information.
PET/MRI
• PET/MRI is a hybrid imaging
technology that incorporates
magnetic resonance imaging (MRI)
soft tissue morphological imaging
and positron emission tomography
(PET) functional imaging.

• Simultaneous PET/MR detection

was first demonstrated in 1997,
however it took another 13 years,
and new detector technologies, for
clinical systems to become
commercially available.
SIGNA PET/MR from GE at Uppsala University Hospital and
Umeå University Hospital.
 PET-MR hybrid imaging

Whole-body PET-MRI scanning:

• (A) Coronal plane of fast T2-weighted MRI, from

skull to mid-thigh.
• (B) Coronal maximum intensity projection of a
PET image.
• (C) Fused Image of whole-body PET and MRI.
PET-MRI of Spine and Breast
PET-CT vs. PET-MRI
PET-CT
•choice of modality for
oncological applications (yet)

PET-MRI
• superior soft tissue contrast
resolution
•minimized radiation
Conventional Nuclear Imaging
Nuclear Medicine
Medical specialty where unsealed sources of radioactivity are
administered in the form of radiopharmaceuticals are used for
diagnostic and therapeutic purposes

Radioactive dose Patient Detection Image

Overview of clinical applications
Thyroid Bone White blood cells (WBC) Cardiac

Brain tumors Brain structures Sentinel lymph node Adrenal

01
Endocrine System
Thyroid Scintigraphy

Radionuclides

 131 lodine

 123 lodine

 [99mTc]pertechnetate

Portulano et al Endocr Rev (2014)

Detection of thyroid disease

Healthy Graves disease and hypo-

functioning nodule

Scintiscans 3h post oral dose 123lodine (200 µCi)

Mello & McDougall. Crit Rev Clin Lab Sci (1992)

Normal iodine-123 scan of the thyroid.

• The normal bilobed gland

with an inferior isthmus is
easily appreciated.

• Note that no salivary gland

activity is seen.
Clinical Indications for Thyroid Scintigraphy and Uptakes

• THYROID SCANS:
 Determination of functional status (cold, hot) of thyroid nodule
 Detection of ectopic thyroid tissue (lingual thyroid)
 Differential diagnosis of mediastinal masses (substernal goiter)
 Thyroid cancer: whole body scan
Appearance of the thyroid on technetium-99m pertechnetate
scans.
• A: Normal. The thyroid is clearly visible, and
the salivary glands are also seen but are
somewhat less intense in activity.
• B: Graves disease. The thyroid is enlarged and
has accumulated much of the activity, so that
the salivary glands are harder to see.
• C: Hyperfunctioning “hot” nodule. The nodule is
seen as an area of intense activity, and its
autonomous hormone production has suppressed
the remainder of the thyroid gland, so that the
normal thyroid is hard to see.
• D: Subacute thyroiditis. In this case, the
inflammation has caused the thyroid to have
difficulty trapping, and the amount of activity
in the thyroid is lower than normally expected,
whereas the salivary gland activity is normal.
Autonomously functioning thyroid nodule

a. An anterior 99mTc thyroid image

reveals a focus of increased uptake
in the lower pole of the right lobe
consistent with a hyperfunctioning
nodule. The normal extranodular
thyroid activity is indicative of
euthyroidism.
b. A focus of markedly increased
activity in the lower pole of the left
lobe accompanied by virtual
complete suppression of extranodular
activity and decreased background
and salivary gland activity is
consistent with toxic adenoma.
Subtle cold nodule

99m
Tc pertechnetate anterior view a demonstrates a subtle hypofunctioning left lower pole
nodule extending into the isthmus, confirmed on a subsequent contrast-enhanced CT b to
be a thyroid cyst.
Multinodular goiter
• Technetium-99m
pertechnetate planar images
of the neck demonstrate
patchy activity in both lobes
of the enlarged thyroid.
• The thyroid gland show
multiple “hot” and “cold”
areas in the gland,
compatible with the typical
appearance of multinodular
goiter.
Diffuse Goiter
Subacute thyroiditis

An anterior 99mTc image reveals markedly reduced activity in

the thyroid bed as compared to background and salivary
glands.
Subacute and chronic thyroiditis
• Image of the thyroid from
an iodine-123 scan in a
patient with chronic
thyroiditis shows patchy or
inhomogeneous activity
throughout the gland.
• This pattern is also seen
with multinodular goiter.
Nonfunctioning thyroid adenoma
• A technetium-99m
pertechnetate scan shows a
“cold” area in the superior
lateral aspect of the right
lobe (arrows).
• A thyroid carcinoma may
present an identical
appearance.
Lingual thyroid
• Anterior and lateral views of the
cervical region from a
technetium- 99m pertechnetate
study demonstrate no activity in
the region of the thyroid bed, but
a focal area of increased activity
is seen high in the midline of the
neck near the base of the tongue
(arrows), compatible with a
lingual thyroid.
• The patient was clinically
hypothyroid.
 Substernal thyroid

A radioiodine scan shows the

thyroid extending inferiorly
into the chest.

Axial CT scan shows the goiter with

a few calcifications interposed
between the trachea and aortic
arch.
Thyroid carcinoma
• Technetium-99m (99mTc)
sestamibi scan shows a large
area of increased uptake in
the right lobe of the thyroid
with a central cold area of
necrosis. The activity
99mTc Sestamibi 99mTc Sestamibi
decreases over 2 hours.
• 99mTc pertechnetate scan
shows the normal gland but
no activity in this area
because the cancer is unable
to trap or organify.
99mTc Sestamibi 99mTc-pertechnetate
Medullary carcinoma of the thyroid
• Somatostatin receptor scan
with 111In-pentetreotide in
patient with an elevated
serum calcitonin level
shows a focus of increased
activity in the neck.

Ant Post
Pulmonary metastases from thyroid carcinoma

Anterior and posterior images of a whole-body iodine-131 scan obtained 72 hours

after injection. Normal physiologic activity is seen in the mouth and salivary
glands, stomach, colon, and bladder. The activity in the lower neck represents
functioning nodal metastases, and the activity in the lung is due to many tiny
hematogenous pulmonary metastases, which are seen on the chest radiograph.
Parathyroid
• Procedure imaging time: 2
hours
• Radiopharmaceutical:
99mTc-sestamibi
• Method of administration: IV
administration
• Normal adult administered
activity: 20 mCi (740 MBq)
• Injection-to-imaging time: 5
minutes
Normal and aberrant distribution of the
parathyroid glands
Normal parathyroid scan

Immediate ant Ant 2 hr

An immediate technetium-99m Sestamibi image of the chest and neck shows activity in
the parotids, salivary glands, thyroid, and left ventricle. On the 2-hour image, the
thyroid activity has faded almost completely, whereas the other areas remain mostly
unchanged. The individual normal parathyroid glands are not seen.
Detection of parathyroid adenomas
Patient with a history of hypertension presented high serum
calcium levels.

Early phase Late phase (3hr)

Intravenous dose of [99mTc]Sestamibi

Benard et al J Nucl Med (1995)
Preoperative localization of parathyroid
adenomas
Patient with hyperparathyroidism

Early phase (15 min) Late phase (2hr)

Intravenous dose of [99mTc]Sestamibi (20 −25 mCi)

Taillefer et al J Nucl Med (1992)
Preoperative localization of parathyroid adenomas

Parathyroid adenoma (located at the inferior aspect of the right lobe of

the thyroid) is present as an area of increased activity relative to the
thyroid on the delayed images. SPECT/CT scan precisely localizes the
lesion.
02
Neuroendocrine Tumors
Meta[131l]-iodobenzylguanidine (MlBG)
therapy for neuroendocrine tumors
Pheochromocytoma (PHEO) Paraganglioma (PGL) of the Radionuclide
Adrenal gland tumor head and neck
[131I]MIBG therapy in pediatric PHEO/PGL
metastasis

Fitzgerald et al Ann N Y Acad Sci (2006)

Intravenous administration of Goldsby and Fitzgerald J Nucl Med Biol (2008)
860 mCi of 131I−MIBG over 2h
03
Skeletal System
Bone scintigraphy to detect osteoblastic
activity
Radionuclides

unmineralized

 [99mTc]methylene diphosphonate
([99mTc]MDP)

Mineralized
 [99mTc]medronate

Mineralization  [18F]Sodium Fluoride

Rauch & Schoenau Arch Dis Child Fetal Neonatal Ed (2002)

Indications for Radionuclide Bone Scan
• Tumors Primary: benign, • Trauma
malignant • Infection: osteomyelitis,
• Secondary: prostate, septic arthritis
breast, lung cancer • Unexplained
• Surgery Joint prostheses musculoskeletal pain
• Bone viability • Abnormal bone
• Metabolic bone disease biochemistry
• Diskitis • Pediatrics Suspected non-
accidental injury
Normal adult bone scan
• Radiopharmaceutical: 99mtc methylene
diphosphonate (MDP)
• Activity administered: 600 MBq (15
mCi) 800 MBq (20 mCi) for SPECT
• Scaled dose based on weight for
pediatric patients
• Patient preparation good hydration;
• Empty bladder prior to imaging
• Collimator low-energy, high-resolution
• Imaging dual-head camera—scan speed
8–10 cm/min
• Spot views—minimum 500 kcounts per
view

Anterior (left) and posterior

images.
Normal adolescent bone scan

15-year-old boy. Anterior (left) and posterior (right)

images demonstrate markedly increased activity
around the epiphyseal plates. This is usually best
seen around the knees, ankles, shoulders, and
wrists.
Visualizing avascular necrosis and
osteosarcoma
Healthy Avascular necrosis Osteosarcoma

Recommended dose for children is 9.3 MBq/kg

(0.25mCi/kg)
Moriguchi et al Clinical Application of Nuclear Medicine Ch 3 (2013)
Immunoscintigraphy for soft tissue infections
Osteomyelitis
Radionuclides

 111lndium−oxine

 Tc−HMPAO
99m

(hexamethylpropyleneamine oxime)

Lydia V Kibiuik CMI (2010)

Detection of osteomyelitis using bone and
immunoscintigraphy
Bone
White blood cell (WBC) WBC (mAb fragment)

[99mTc]MDP (750 MBq) WBC labeled with mAb Fab' fragment (1.25 mg) labeled with
[111ln]oxine (20 MBq) [99mTc]pertechnetate (1000−1500 MBq)

Becker et al. J Nucl Med (1994)

Metastatic prostate cancer

Anterior view shows the metastatic

deposits as areas of increased activity.
SPECT/CT scan shows the osseous
metastases. Note, however, that the
lymphadenopathy (arrows) is seen on
only the CT portion of the study
Superscan
• Diffuse osteoblastic
metastases from carcinoma of
the prostate.
• There is involvement of the
entire axial and proximal
appendicular skeleton.
• There is minimal renal or
bladder activity identified
because the metastases have
accumulated most of the
radionuclide.
Sternal metastasis
• Young woman treated for
breast cancer 1 year earlier.
• The follow-up bone scan
reveals only one focus of
increased activity, which isin
the sternum.
• Round or eccentric sternal
lesions in breast cancer
patients have about an 80%
chance of being a metastasis.
Osteogenic sarcoma
• Radiograph (left) reveals
mottled sclerosis and
periosteal reaction in the
proximal tibia of a
teenager.
• Right, Increased activity is
seen on the bone scan as
well. There is normal
physiologic activity seen at
the epiphyseal plate.
Metastases from renal carcinoma
• Absent left kidney
(nephrectomy)
Osteolytic metastases from primary renal carcinoma

Oblique spot views of the skull and pelvis

Causes of Cold Lesions on Bone Scan
• Localized
 Overlying attenuation artifact caused by pacemaker, barium, etc.
 Instrumentation artifact
 Radiation therapy
 Local vascular compromise
 Infarction
 Intrinsic vascular lesion
 Early aseptic necrosis
 Marrow involvement by tumor
 Early osteomyelitis
 Osseous metastases from: Neuroblastoma, Renal cell carcinoma, Thyroid carcinoma, Anaplastic tumors
(e.g., reticulum cell sarcoma), Cyst
• Generalized
 Older age
 Inadequate amount of radiopharmaceutical
 Chemotherapy
Hypertrophic pulmonary osteoarthropathy

Affecting femora and tibiae, with

spinal and rib metastases and left
pleural effusion, secondary to bronchial
carcinoma.
Osteoid osteoma of the left mid-tibia

Left, bone scan. The intense uptake is

characteristic of these lesions. Right,
Lateral radiographic view demonstrates the
lesion with a central nidus.
Typical Activity of Benign Bone Tumors on Bone Scans
• Intense • Mild or Isointense
• Fibrous dysplasia • Fibrous cortical defect
• Giant cell tumor • Bone island
• Aneurysmal bone cyst • Cortical desmoid
• Nonossifying fibroma
• Osteoblastoma
• Osteoma
• Osteoid osteoma
• “Cold”
• Moderate • Bone cyst without fracture
• Adamantinoma
• Variable
• Chondroblastoma
• Hemangioma
• Enchondroma • Multiple hereditary exostosis
04
Cardiovascular System
Myocardial perfusion imaging for ischemia
detection
Ischemia Radionuclides

 201 Thallium chloride

 [99mTc]sestamibi (cardiolite)

 [99mTc]tetrofosmim (myoview)

Thygesen et al Circulation (2012)

Basic principles of myocardial perfusion
imaging
• Inject radioactive tracers whose distribution in the heart are
proportional to the amount of blood flow to the area
• Gamma camera detects the photons given off by the
radioactive tracers and thus the relative blood flow to the
different areas during rest and stress
• Detects RELATIVE, not ABSOLUTE blood flow
• May miss “balanced ischemia” if blood flow to all areas are
reduced in the case of 3 vessel disease.
 Commonly used tracers

• Technetium 99m Sestamibi

• Technetium 99m is a radioactive compound, sestamibi is a small cation that has been labeled
with Technetium 99m. Binds the mitochondrial membrane
• ½ life of 6 hours
• Better imaging characteristics (intrinsically better and also because can inject higher dose
since ½ life is shorter)
• Does not show “redistribution”
• Thallium
• Radioactive K analog. Enters/exits cell via Na/K ATPase
• ½ life of 3 days (more radioactive exposure to patients)
• Worse imaging characteristics (intrinsically worse and also because need to limit dose to
limit radioactive exposure)
• Shows “redistribution”- after injection, the tracer moves to viable parts of the myocardium
that initially shows less uptake
Commonly used protocols
• Low dose, high dose Tc99m • Dual isotope (thallium, Tc99m
sestamibi same day protocol: sestamibi) same day protocol:
• Inject low dose of the tracer at rest • Inject thallium 201 at rest
• Acquire images • Acquire images
• wait several hours for the tracers to • Stress the patient, inject Tc99m
decay (so that the rest pictures sestamibi
wouldn’t interfere with the • Acquire images
interpretation of the stress
pictures) • Advantage is that thallium and
Tc99m gives off slightly different
• stress the patient, iinject a higher energy of photons so pictures from
dose of the tracer at peak stress the rest wouldn’t “contaminate”
• Acquire images again the picture at stress
• Compare the pictures • Problems includes more radioactive
• Most commonly used here. exposure and difficulty in
comparing thallium with Tc99m
images.
Other protocols
• Two days Tc99m sestamibi • Thallium-redistribution
protocol -same sequence as the protocol:
1 day protocol except • Stress the patient and inject
• Inject high dose of tracer for the tracer at peak stress
rest and stress (don’t have to • Image the patient immediately
worry about high dose at rest • Wait 3-4 hours and image the
contaminating the stress patient again (because tracer
pictures since there is adequate shows redistribution, it will
time for the tracer to decay)- move to areas that are alive
gets better quality rest pictures there will be a difference
• Wait 1 day between the stress between the stress and rest
and rest images image if there is ischemia)
• Better for obese patients • Can wait 24 hours to assess
• Obviously, time delay can be viability (areas with little life
inconvenient. will light up much later)
Vasodilator stress test

• Causes hyperemia but does not increase workload!

Can only be performed with nuclear perfusion imaging
• Can be safely performed soon after uncomplicated
acute coronary syndrome (safety tested 2 days after
ACS) Brown KA et al. Circulation 100:2060, 1999
• May decrease the amount of false positive anterior-
septal defects in patients with LBBB compared to an
exercise stress test.
• The absence of EKG changes does not indicate the
absence of CAD. However, the presence of EKG
changes is a very bad prognostic factor.
Dypyridamole/Adenosine
• Adenosine is a small molecule with the following effects:
• Activation of the A2A receptors causes coronary vasodilatation- making this a
useful agent for stress testing.
• Activation of A1 receptors causes atrioventricular (AV) conduction delay, explaining its use in the
management of supraventricular arrhythmia
• Activation of A2B, A3, A4 receptors can mediate bronchospasm
• Methylxanthines (like caffeine, theophylline, aminophylline) are adenosine antagonists.

• Dypyridamole blocks the metabolism and therefore causes the build up of

adenosine.
• Half life of 40-80 mintues, reversed with aminophylline.
• Cautious use in patients with hepatic dysfunction
Diagnosis
• Thallium SPECT- sensitivity of 88% and
specificity of 77%
• EKG stress test- sensitivity 68%, specificity 77%.
• Stress echocardiography- sensitivity of 76% and
specificity of 88%
• In general, nuclear myocardial stress imaging
considered more sensitive and less specific then
stress echocardiography.
• Referral bias- only the people with positive ETT
goes on to have the gold standard test. Hence, true
sensitivity is probably lower, true specificity higher.
Example of a normal scan
(uniform uptake during rest and stress)
Dual Isotope 201Tl/ 99mTc cardiac SPECT
imaging
Case study I: patient with a clear anterior defect Case study II: patient with a lateral defect

Stress −99mTc, energy window: 126−43 keV Cerqueira and Ferreira. Clin Nucl Med. Ch 4 (2007)
Rest −201Tl, energy window: 68 −77 keV
Gated Imaging
• Divides the cardiac cycle into
phases
• Data collected during each
phase is pooled to form a
single image
• Images from each phase are
put together to compose a
series of images called a cine
• Further information can then
be obtained from this data by
applying computer algorithms
 Gated Imaging

• 3D images allow for accurate quantification of volumes in each phase of the cardiac
cycle
• Calculated by using computerized edge detection to determine the endocardial border
• LVEF = 1-(ESV/EDV)- good correlation with echo and CMR.
• To get accurate quantification, the computer must be able to accurately detect the
endocardium
• Needs regular rhythm
• Motion or other artifacts that significantly affect the perfusion images can reduce accuracy
• Severe defects (real or attenuation) is a problem
• No counts, no border
• Small hearts- resolution not high enough to be accurate
Myocardial perfusion gated SPECT images obtained after injection of radiotracer prior to PCI (SPECT-1)
and 1 month after AMI (SPECT-2) in (a) 56-year- old man with at-risk myocardium area of 97 cm2 and
salvaged myocardium area of 11 cm2 and (b) 60-year-old man with an at-risk myocardium area of 83 cm2.
Imaging the blood
• The logic behind this is that as the
blood volume changes during systole
and diastole, it is representing the
movement of the myocardium.
• The RBCs are labelled in vivo by
injecting stannous pyrophosphate
which adheres to the red cell
membrane, followed by 800 MBq
99m Tc as pertechnetate, which
then sticks to the red cells. The
study is gated, and is known as a
MUGA (Multiple Gated Acquisition)
study.
Multiple Gated Acquisition
• Computer analysis allows
the LV ejection fraction
(LVEF) to be easily
calculated.
• ROIs drawn at end-systole
ES and end-diastole ED,
together with the
background.
• The volume curve allows
the EF to be calculated.
05
Lymfoscintigraphy
Lymphoscintigraphy for sentinel lymph node
mapping
Radiolabel injection Imaging Therapeutic Intervention

[99mTc]sulfur−colloid (TSC)
[99mTc]tilmanocept (TcTM)
Wilson T. National Cancer Institute (2010)
Breast lymphoscintigraphy

Lymphoscintigraphic images 30 min post intradermal TSC (0.1−0.5 mCi) injection

Pandit−Taskar et al. J Nucl Med (2006)

Radio-guided surgery using hybrid gamma-
optical imaging

ICG − fluorescent dye Portable gamma camera Optical and gamma−imaging Fused image
[99mTc]nanocolloid

IS − Injection site, SN − Sentinel node

Hellingman et al Clin Nucl Med (2016)

Roadmap for surgeon by Nuclear Medicine
Nuclear Medicine and Sentinel Node

• To find and localize SN

• Site / sites are marked on
skin before the operation
• Marking from various
directions (if necessary)
06
Central Nervous System
Brain Radiopharmaceuticals Used Clinically
• Blood–brain barrier
• Tc-99m glucoheptonate
• Tc-99m DTPA
• Brain perfusion
• I-123 iodoamphetamine (IMP)
• Tc-99m HMPAO
• Tc-99m methyl cysteinate dimer (ECD)
• Brain tumor imaging
• Thallium-201
• Tc-99m sestamibi
• Cisternography
• In-111 DTPA
• Tc-99m DTPA
Brain perfusion
• A brain perfusion scan is a type of brain test that shows the
amount of blood taken up in certain areas of your brain.
• This can provide information on how the brain is functioning:
 Epilepsy
 Dementia
 Stroke or transient ischemic attack
 Subarachnoid hemorrhage
 Carotid stenosis
 Cerebral vasculitis
 Brain tumor
 Recent head injury  
Normal brain perfusion SPECT

99mTc-ECD SPECT Brain Perfusion

Usual pattern of radiopharmaceutical distribution in brain parenchyma.
Brain Death
• Visualize perfusion in the brain
 Tc-99m HMPAO
 Tc-99m ECD
• Lateral and anterior images.
• Complete absence of brain activity within the brain
indicates no cerebral blood flow.
• Any activity within the calvarium means that there is some
area of brain that is still perfusing and this would be
negative for brain death.
 (Left) Anterior image of a patient injected with Tc-99m
Brain Death HMPAO demonstrates no visible brain activity. Note the hot nose
sign.
(Right) Lateral image of the same patient demonstrates no visible
brain activity, consistent with brain death.
 Brain tumor imaging in high-grade gliomas

Differentiation of tumor
recurrence from radiation
necrosis using 201Tl-
SPECT.
 Brain tumor imaging in Glioblastoma multiforme (GBM)

Post-treatment MRI scan with intravenous

gadolinium enhancement shows increased
wall thickness, with enhancement. These
could represent viable tumor or postradiation
therapy inflammation.

99m Technetium methoxyisobutylisonitrile
(MIBI) SPECT/CT shows selectively increased
uptake in the wall of the mass. Normal brain
parenchyma does not show uptake.
Physiological uptake by the choroid plexus is
more prominent.
Cisternography
• Study of cerebrospinal fluid (CSF) dynamics using
radiotracers
 diagnose a site of CSF leakage
 determine shunt patency
 manage hydrocephalus
• CT and MRI are now often used, radionuclide cisternography
can still play an important role
• To be effective, close coordination with structural imaging
studies and detailed knowledge of the clinical problem are
necessary
 Radionuclide cisternography

Radionuclide cisternography was performed for

detection of CSF leak 24 hours after the injection of
55.5MBq of In-DTPA intrathecally. Focal asymmetry of
radioactivity (blue open arrow) was noted in the left
temporal region on the cisternographic images
obtained at 24 hours post injection of the tracer,
which may have represented a CSF leak or asymmetric
distribution of CSF radiotracer activity due to normal
variant of asymmetry of CSF spaces or anatomic
changes from prior surgery or trauma.
 Radionuclide cisternography
Anatomic localization of asymmetric radioactivity on
cisternography to enlarged CSF space in the left middle
cranial fossa by SPET/CT with correlated brain MRI.
On the SPECT/CT images, asymmetric radiotracer
activity was found to be localized within an enlarged
CSF space in the left middle cranial fossa (A: white open
arrow), corresponding to an enlarged CSF space in the
left middle cranial fossa seen on T2 weighted images
from a prior MRI performed 6 months earlier (B: thick
red solid arrow).
This enlarged CSF space in the left temporal region was
caused by prior resection of a left temporal arachnoid
cyst performed both eight years and two years ago.
07
Lung
Ventilation Scintigraphy
Ventilation can be performed with radioactive gases or
labeled aerosols.
• Xenon and Krypton (133Xe, 127Xe and 81mKr)
• Radioaerosols are an alternative to radioactive gases.
 Technegas, regarded as a pseudogas because of its very small particle size,
giving aerodynamic properties simulating a gas.
 Diethylene triamine pentaacetate (DTPA) labeled with technetium 99m is a
frequently used agent.
• Commercial nebulizers are available that provide particles of
appropriate size. The ideal ones are in the range of 0.1- 0.5 µm.
Particles larger than 2- 3 µm tend to settle out on large airways.
Perfusion Scintigraphy
• Perfusion scintigraphy is accomplished by microembolization with radiolabeled
particles injected in a peripheral vein.
• The commercially used particles are macroaggregate of human albumin (MAA),
marked with 99mTc.
• 15-100 µm in size and will lodge in the pulmonary capillaries and precapillary
arterioles. The particle distribution accurately illustrates regional perfusion.
• Normally, about 400,000 labeled particles are injected.
 There are over 280 billion pulmonary capillaries and 300 million precapillary arterioles,
the routinely administered particles will result in obstruction of only a very small fraction
of pulmonary vessels.
• A special preparation of 100,000-200,000 particles is usually given to patients
with known pulmonary hypertension, right to left heart shunt or after a single
lung transplantation.
Overview image of ventilation and perfusion in frontal and
sagittal slices.

Marika Bajc breathe 2012;9:48-60

 Patient with Chronic Obstructive Pulmonary Disease and PE

Coronal slices; very uneven

distribution of ventilation with
deposition of aerosols in small
airways (upper row). Multiple
segmental and subsegmental
perfusion defects (arrows) in
ventilated areas, well delineated on
V/Pquotient images.
Ventilation study with Technegas and DTPA

Patient with COPD. Coronal slices

 V/P quotient images

Subsegmental Lobar defect in

perfusion defects in the left lung
the right lung (arrow). (arrow).
Pulmonary Embolism - V/PSPECT Method
Massive PE, initially and at 4 days and 1 month
follow-up.
Conventional and SPECT Lung Imaging
• Scintigraphic lung studies are designed to demonstrate
patterns of ventilation and perfusion.
• In the healthy individual there is a balance between regional
perfusion and ventilation to achieve optimal gas exchange.
• When a pulmonary disease causes a deficiency in both
ventilation and perfusion, they are mismatched. Mismatch
implies an imbalance between perfusion and ventilation.
• The most important application of lung scintigraphy is the
evaluation of patients with suspected pulmonary embolism
(PE).
08
Liver, Spleen and Biliary Tree
Biliary Excretion

Radiopharmaceuticals: 99mTc labeled iminodiacetic acid

(IDA) derivatives
 DISIDA (2, 6 diisopropylacetanilido-iminodiacetic acid)
 BRIDA (bromo 2, 4, 6 trimethylacetanil-idoiminodiacetic acid)
 HIDA (iminodiacetic acid;dimethyl-iminodiacetic acid)
 EIDA (diethyl-iminodiacetic acid)
• Normal Tc-99m HIDA 60-
minute study (1-minute
frames). Good hepatic
uptake. Blood pool clears
by 7 minutes, consistent
with good hepatic function.
Gallbladder fills early, then
bile duct visualization and
biliary-to-bowel transit
PET-CT Imaging
Basics of PET Imaging
• Uses short lived positron emitting isotopes (produced by
cyclotron)
• Two gamma rays are produced from the annihilation of each
positron and can be detected by specialized gamma cameras
• Resulting image show the distribution of isotopes
• An agent is used to bind into isotopes (glucose, …)
• Late 1950s, david L. Kuhl
 concept of emission and transmission
 molecular activity is measured

60
𝟏𝟖𝑭-fluoro-2-deoxy-D-glucose (FDG)
• Most common radiotracer used in
80% of PET studies
• FDG injected into blood stream →
transported to cells across body
• Uptake depends on rate of
glucose utilization = glucose
metabolism:
 High glucose metabolic rate
characteristic of many tumours →
hot spots in oncological PET
scans.
How FDG Works?
• Following injection, during the distribution phase (usually one hour) cells take
up and phosphorylate FDG. Non-phosphorylated FDG is excreted by the kidneys.

• Phosphorylated FDG does not proceed to the next step in glycolysis due to
altered configuration (substitution of Fluorine for a hydroxyl group).

• Malignant cells demonstrate a difference in accumulation due to increased cell

membrane transporters and underexpression of glucose 6-phosphatase.

• This leads to a greater tumor to background uptake, thereby differentiating

malignant lesions from benign tissue.
Normal FDG Uptake
• Brain: greater uptake in the cerebral cortex, basal ganglia and thalami
(grey matter)
• Head and Neck: vocal cords, tonsils, parotid and submandibular
glands.
• Thyroid: Focal and diffuse uptake patterns.
• Brown fat: various sites of symmetrical uptake in the neck,
supraclavicular regions, axilla, mediastinum.
• Skeletal muscle: diaphragmatic crura, intercostal, psoas,
paravertebral muscles.
• Myocardium: variable from absent to diffuse increased FDG activity
• Lungs: usually low uptake
• Mediastinum: Nonspecific hilar uptake
• Breast and Nipples: Mild uptake in young and post-menopausal women
on hormone replacement therapy
• Liver: heterogenous or patchy uptake
• Splenic: Normally less or similar uptake as Liver; but increased uptake
Post GCSF treatment
• GI: variable activity involving esophagus, GE junction, stomach,
pylorus, small and large bowel, patients on metformin
• GU: excreted activity; mild uptake in normal adrenal glands.
• Pelvic organ: Uptake in ovaries and endometrial canal (during
menstruation).Mild uptake in the testis.
• Bone marrow: Normally similar uptake as Liver but increased uptake
Post GCSF treatment.
• Lymph node: Minimal uptake; increased uptake due to extravasation.
Normal NaF bone scan using PET…
PET-CT in Oncology
Abnormal PET-CT Body Scan
Common Oncologic Applications
• Initial staging of biopsy proven cancer (prior to any
treatment)
• Restaging after irradiation, chemotherapy, or surgical
resection.
• Rarely, diagnosis of malignancy. e.g. indeterminate solitary
pulmonary nodule on CT scan
Hodgkin’s Lymphoma
Quantification – what to measure in PET?
• SUV (standardized uptake value): SUVpeak, SUVmax, SUVlbm

• Metabolic lesion/tumor volume (MTV)

• Shape information of (functional) lesion (spiculated vs focal)

• Texture information of lesion (heterogeneous vs homogeneous)

• Number and distribution of the lesions (focal, multifocal)

FDG-PET has Low Sensitivity for:
• Prostate Cancer [C-11 Acetate PET shows promise]
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Mucinous carcinomas
• Neuroendocrine tumors [use MIBG instead]
• Bronchioalveolar carcinoma
• Teratoma or ovarian adenocarcinoma
• CNS neoplasms [due to high background uptake]*
• Villous adenomas
• Adrenal Adenomas
Lesion Characterization
47 year old man with multiple
trauma from a MVA who was
incidentally discovered to have
a pulmonary nodule
Lesion Characterization

84 year old man with chronic

cough found to have a 13 mm
nodule on CXR
 Enhanced Detection

73 year old woman s/p resection for colon cancer, rising CEA level and negative
CT
Enhanced Detection
Enhanced Detection

70 y/o male with

H&N cancer
Enhanced Detection
47 year old man
with biopsy
proven recurrent
thyroid cancer 3
months after
thyroidectomy

I-131 FDG PET

Staging melanoma with extended field-of-view

27 year-old female with metastatic melanoma.

Uptake in left lower extremity and in left axillar node
positive for melanoma.
 Unknown Primary

68 year old man who presented with right neck mass

 Staging

49 year old man with new lung cancer

 Recurrent Disease

64 year old man s/p laryngectomy,

now has dysphagia.
 Monitoring Response

63 year old man stage 3A lung cancer, has received 4 cycles of chemotherapy
Problems and Pitfalls
• False negative findings
• Tumor histology
• Lesions smaller than 8 mm
• Diabetes/Non-fasting patients

• False positive findings

• Normal physiology
• Granulomas and other infections
• Adenomas
Infection

68 year old man with solitary lung nodule. Biopsy: aspergillosis

Granulomatous Disease

62 year old man with hilar and

mediastinal adenopathy. Biopsy:
sarcoidosis.
Adenoma

82 year old man with wt loss and liver

masses
Cardiac PET/CT studies
• Used for the study of
coronary artery diseases →
• perfusion and myocardial
viability

• PET-CT use in cardiac

studies is increasing →
where available is used
instead of SPECT
Cardiac PET/CT studies

Ammonia PET : Dilated Cardiomyopathy

Summary

• False negative FDG PET can be reduced by careful patient

selection for appropriateness and proper preparation.

• False positive FDG PET can be reduced by correlation with

CT and knowledge of potential pitfalls.
Clinical Impact of PET/CT

• More accurate diagnosis

• Avoidance of unnecessary tests, and (potentially) harmful

procedures

• Better treatment or management

 Future tracers…in Iasi

Other (target-specific) radiopharmaceuticals:

• Na18F for bone scans for non-FDG avid metastatic disease

• 18F-fluorothymidine-FLT
• 18F-fluorocholine:11C-choline;
• 68Ga-for prostate cancer
• Ammonia (13NH3) imaging for cardiac lesions
PET-CT with 18F-fluoride NaF
Imaging bone
metastases of lung,
prostate, breast
cancers

Not tumor specific:

marker of osteoblast
metabolism

Groves AM, Win T, Haim SB, Ell PJ. Non-[18F]FDG PET in clinical
oncology. Lancet Oncol. 2007;8:822-30. Review.
18F-fluorothymidine: FLT
• FLT is transported from the blood
into cells by active transport and
phosphorylated by thymidine kinase
I without incorporation into the
DNA. 
• The accumulated activity in the
cells is proportional to thymidine
kinase I activity as well as cellular
proliferation.
• 18F-FLT is a marker for tumour cell
proliferation that has been
introduced to improve the accuracy
of early FDG PET assessment
Choline: 11C-choline; 18F-fluorocholine
• The uptake of choline:
• high-affinity, sodium dependent choline
transporter (CHT),requires ATP as an energy
source.
• the activation of low-affinity, sodium-
independent organic cation transport
proteins (OCTs) and/or carnitine/organic
cation transporters (OCTNs), and do not
require ATP.
• intermediate-affinity transporters, which
include the choline transporter-like protein 1.
• The main clinical application of choline is
in prostate cancer patients for staging and
restaging the disease in case of
biochemical recurrence after primary
treatment.
CH3[11C]O2: 11C-acetate
• 11C-acetate is typically incorporated into
the cellular membrane in proportion to the
cellular proliferation rate or alternatively
oxidised to carbon dioxide and water.
• 11C-acetate may also be converted into
amino acids. 
• The main clinical application of 11C-acetate
is the detection of non 18F-FDG-avid
neoplasm
• differentiated hepatocellular carcinoma
• renal cell carcinomas.
• Some other applications of 11C-acetate PET
• brain tumours
• lung carcinomas
• in the past the tracer has been used in prostate
cancer.
11C-acetate, staging hepatocellular carcinoma (HCC), comparison with 18F-FDG

11C-acetate 18F-FDG
 18F-fluoroestradiol: FES
• 18F-fluoroestradiol binds to the
oestrogen receptors on the
tumour cell surface as well as
intratumoural receptors in
oestrogen receptor-positive
tumours.
•  18F-fluoroestradiol is a
valuable tracer for the studies
of the oestrogen receptor
status of primary and
metastatic breast or ovarian
cancers .
18F-fluoroestradiol, breast cancer, characterisation of brain
metastasis.
Thank you!
 Post Prandial Scan

57 year old man with stage IV left tonsillar SCC treated with chemoradiation 21 months ago. Patient
was lost to follow-up until he was referred for PET/CT. Coronal images show low FDG uptake in the
brain, and high uptake in the heart and skeletal muscles.
 Post Prandial Scan

• Fasting:
Euglycemia
6 hours
Diabetes
12 hours

fed 04/25 fasting 05/08

Hyperglycemia

69 year old man with 2.3 cm RUL NSC lung cancer. FBS = 309 mg/dL. No insulin
was given. Coronal images show a good quality scan with high FDG tumor uptake
(max SUV 5.4)
Insulin Effect on FDG uptake

63 year old man with 5 cm RUL adenocarcinoma. FBS = 299 mg/dL; 90 minutes
after 15u of reg insulin IV FBS = 179 mg/dL at which time FDG was injected.
Coronal images show a “muscle scan” with faint tumor uptake (max SUV = 2.0)
Fasting = Less Cardiac Uptake
Fasting Scan in a Diabetic

51 year old man with colon polyps and a stricture referred for PET/CT to
evaluate for possible malignancy. Fasting blood glucose level = 289 mg/dL.
Coronal images show a good quality scan with normal FDG biodistribution..
Normal PET/CT scan

PET
CT PET/CT
Physiologic Uptake: Brown Fat
Non-malignant causes of FDG uptake
• Inflammatory changes
• Inflammatory bowel disease [CRP is usually also elevated]
• Reflux esophagitis & Gastritis
• Active granulomatous disease
• Pneumonitis
• Radiation-induced inflammation
• Conjunctivitis
• Degenerative joint disease

• Post-Exercise increased muscle uptake

• Hyperinsulinemia (increased muscle uptake)
Infection

68 year old man with solitary lung nodule.

Biopsy: aspergillosis
 Granulomatous Disease

62 year old man with hilar and mediastinal

adenopathy. Biopsy: sarcoidosis
 Miscellaneous Causes
Thyroiditis
 Miscellaneous Causes
Rib Fracture
 Gastritis, Inflammatory Hilar Nodes

*Usually it is difficult to
differentiate physiologic vs
inflammatory uptake on
PET alone

Normal Patchy atrial Uptake;

This patient was likely not fasting