PET : Quantitative imaging technology
Hokkaido University Hospital Department of
Nuclear Medicine Chietsugu Katoh, MD, Prof.
PET （Positron Emission Tomography）:
Radioactivity quantitative measurement
device that calculates the distribution of
positron emitting nuclides in the body inthree dimensions and four dimensions• High resolution (good image quality)• High sensitivity• Excellent quantification

18F-FDG (Fluoro Deoxy Glucose) is a substance similar

to glucose, which is taken up by tissues like glucose, but
is not metabolized, stays in the tissues for a long time,and is a useful drug for collecting glucose quantitative
images of brain and lesions.
(However, it is difficult to be taken into hepatocytes andwell-differentiated hepatocellular carcinoma.)(Renal cancer clear cell carcinoma also has poor FDG
uptake.)
HO

HO

HO

HO

D-Glucose
ブドウ糖

O

HO

O

HO

OH
OH

OH

18F-FDG

Analog of Glucose

18FNormalTakayasu Aortitis 高安動脈炎

Lung ca.

18F-FDG PETNormal accumulation in
the brain, urine, andsometimes myocardium,in addition to tumors
and inflammation.

肺癌Generally, body tissues ingest fatty acids as anenergy source and produce ATP (adenosine
triphosphate) from the fatty acids in the betaoxidation cycle in mitochondria.
The beta oxidation cycle produces a lot of ATP
but requires a lot of oxygen.
Abnormal tissues with high density of cells, suchas cancer cells and inflammatory cells, produce
ATP in a glycolytic system that does not require
much oxygen because the blood vessels that are
the passages of red blood cells that carry oxygen
are inadequate.
Glycolysis produces a small amount of ATP, so
in normal tissues, glucose is not used very much.
Then, FDG uptake shows the abnormal tissues.

Hokkaido University Hospital
Nuclear medicine laboratory

ＰＥＴ/ＣＴ装置

ＰＥＴ:
陽電子ＣＴ
Positron
Emission CT

18F-FDG

Brain PET

185MBq 1hour after i.v. 5min.

Diseases covered by FDG-PET
health insurance
1. Epilepsy (intractable, surgical indication)
２．Ischemic heart disease (diagnosis of viability)
Cardiac sarcoidosis (fatal arrhythmia)
３．Malignant tumor (excluding early gastric ca.)
(Cases judged to be malignant by pathologicaldiagnosis, or by other images (CT, MRI, etc.).
Evaluation of the therapeutic effect ofmalignant lymphoma.
Patient with confirmed metastasis.
４． Aortic inflammation(Takayasu arteritis, giant cell arteritis)

Takayasu arteritis
One of the specified intractable diseases (with330 diseases). 7,000 registered patients.
90% are women. The most common age is 10 to
30 years old. Young woman.
In a young woman with severe neck pain, headache, stiffshoulder, CT etc., findings such as stenosis in the
branch vessels of the aortic arch.
If there is a difference between the left and right upper
limb blood pressure measurement values, perform FDG
PET / CT. FDG accumulation in inflamed blood vessels.
Treatment is steroids (relapses easily),
Antibody drug (tricizumab (actemra) IL-6R
Originally rheumatoid arthritis. Expensive. 5000 yen /dayClick on any of the CT, PET and fusion images,
The accumulation of the part is displayed.
The clicked point is indicated by a yellow cross.

Clicked
point
Clickedpart count(radioactivity)

Calculate the SUV of the lesion from the FDG-PET image.

SUV ( Standardized Uptake Value)
Radioactivity concentration of lesion（Bq/ml）= Average body radioactivity concentration (Bq / ml)(Dosage (Bq) / Weight (g))

The radioactivity of the numerator and denominatormust be synchronized (with half-life correction).

Semi-quantitative value indicating how many times
the radioactivity concentration of the lesion is higher
than the body average. The normal value is 1.
2.5 to 3 or more are considered pathologicalaccumulation.

半減期

Ｈａｌｆ ｌｉｆｅ Ｔ１／２
（ ｔ / Ｔ1/2 ）Ｎ ＝ Ｎo ｘ （１／２）

崩壊定数 Decay constant λ
１秒間に原子核が崩壊する割合
Ｎ

Nuclear decay rate per second

Ｎo

ｄＮ／ｄｔ ＝ -λＮ
Ｎ ＝ Ｎo

ｅ

－λｔ

Ｎo／２

Ｎo／２ ＝ Ｎo

Ｎo／４

１／２ ＝

ｔ
Ｔ1/2 ２Ｔ1/2ｅｅ-λＴ1/2-λＴ1/2ｅLog（１／２） ＝ Log （-λＴ1/2 ）Log２ ＝ ０．６９３ ＝ λＴ1/2

Clinical Radiologist National Examination
18F-FDG that was 200 MBq at 10:00 was injected to a patient

at 10:55. PET scanning was started at 11:50, and image
analysis was performed at 13:40.
The radioactivity of the lesion was 12000 Bq/ml. Calculate
the SUV of the lesion.
( The patient's weight is 50 kg, height is 150 cm, and half-lifeof 18F is 110 minutes.)
Calculate the radioactivity at 11:50 of the imaging start time.
The radioactivity in the patient is 200 x (1/2) = 100 MBq
The average concentration in the body is 100 MBq / 50 kg =2000 Bq / ml
Then, SUV in the lesion is 12000 / 2000 = 6.0(There is no quantitative unit for SUV. SUV is semi-quantitative.)FDG-PET after meal showed
SUV 2.2 in the lesion.
Re-study was performed on
fasting, SUV in the lesion
was raised to 3.4
FDG-PET must be performedin the fasting state.

CECT(Contrast enhancement CT)

In the 18F-FDG PET study, the patient should be fasted
and discontinued the sweet drink for 6 hours before.
What is the problem with 18F-FDG PET study performed
without the pretreatment ?
18F-FDG is an analog of glucose. Since glucose

accumulates in tumors and inflammatory lesions,
FDG also accumulates. Without fasting pretreatment,
the patient's blood glucose level increases.
In hyperglycemic conditions, tumors and inflammatory
lesions accumulate much glucose, and FDG
accumulation decreases due to the competition.
Therefore, the uptake of the lesion on the PET image isreduced, and the SUV is also reduced.
This makes it difficult to diagnose the lesion.

Gamma camera
Equipment for imaging the
distribution (scintigram) of
gamma-ray emitting drugs
in the body.

Anterior

Posterior

Distribution image ofphosphoric acid labeled withgamma-emitting RI.
Strongly distributed in bonemetastatic lesions.
A case of lung cancer withbone metastasis in the rightscapula, thoracic andlumbar spines.
Since this RI is excreted inurine much, the urinary tract
and bladder are depicted.

The reason the images taken by the
正面と背面のカメラで撮影した像がanterior and posterior cameras are different
異なる理由は、人体がガンマ線を吸
is that the human body absorbs and
収、散乱させているため。
scatters gamma rays.
The deeper the part from the body surface,
体表から深い部位ほど描画が薄い。

the thinner the depiction.

Annihilation
When a positron is emitted from the positronemitting nuclide, it collides with the electron over arange of several millimeters and annihilates, and apair of 511 keV annihilation radiation is emitted in
the opposite direction.
The positron and the electron have the same mass,
and when they annihilate, a photon (annihilation
radiation) with a value of 511 keV is obtained bysubstituting the electron mass into the equation of
E = mC2.
Electromagnetic waves generated from inside the nucleus are called γ-rays, andelectromagnetic waves generated by the transition of extranuclear orbital electrons
are called X-rays. Annihilation radiation is an electromagnetic wave that does notcorrespond to either.
Positrons are antiparticles of electrons, having a positive charge and negative
energy. When an electron and a positron whose energy and charge are opposite toeach other meet, they disappear and are replaced by electromagnetic wave energy
equivalent to the disappeared mass. Electromagnetic waves have no mass but
energy, so they have momentum. The generated electromagnetic wave flies in the
opposite direction according to the law of conservation of momentum. An accurate
understanding of this phenomenon requires knowledge of quantum mechanics andrelativity.

There are two types of radiation.
１．Electromagnetic waves (X rays, γrays)＝ Vibration energy of space
２．Particle beam (electron, positron etc.)＝ Particle flying at high speed (with mass)
which has greater effect on the humanbody than X-rays and gamma rays.

Radioactivity is the number of radiations
emitted per second.
The unit of radioactivity is Becquerel (Bq).

Electromagnetic wave is the vibration energy ofthe space (X rays, γrays, light rays, radio waves).

Space (or Universe) is not nothing.
The space has a physical entity (structure).

The vibration of the spatial structure
becomes electromagnetic waves such as
X-rays, gamma rays, visible light, etc.
Name and wavelength of electromagnetic wave
X-rays and γ-rays: 10 pico to 10 nano-meters
Visible light : 400 (purple)-800 (red) nano-meters
Microwave: 100 micro to 1 meterMaxwell's formula : the speed of electromagnetic waves
Speed of electromagnetic waves in vacuum :C = 1/ √ μo εo = 300,000 km/s = 3 billion m/s( μo : Vacuum permeability , εo : Vacuum permittivity ）A vacuum (= space) has a structure having magnetic
permeability and permittivity.
＝ Space has a physical structure.
If there is no structure in the space, the magnetic
permeability μo in vacuum (probability of magnetic field)
and the dielectric constant in vacuum εo (probability ofelectric field) should be zero.
If μo = 0 and εo = 0, the electromagnetic wave velocity
in vacuum C = 1/ √ μo εo should be infinite,which contradicts reality.

Photon is interpreted as a particle of energy in the space withzero weight. The particle feature of electromagnetic energy suchas visible light or X-rays was confirmed by Einstein and Compton.
Even on a daily basis, the phenomenon that stars far fromthousands of light years away can be seen in the night sky cannot
be explained without recognizing the particle nature of light, thatis, the existence of photons. If light is just a wave, the wave oflight emitted from the star will spread for thousands of years inouter space, the energy of light reaching the earth will besignificantly weakened, and we should not be able to see distantstars.

It is difficult to understand the duality that the electromagnetic
energy has the feature of both wave and particle. The reason isthat it is difficult for us to recognize space as a structure of four
dimensions or more. If space has only three-dimensional
structure, its duality cannot occur.

PET
camera has high sensitivity because there is no collimator.
PETカメラは、コリメータがないので高感度。
The collimator mounted on the conventional gamma camera is a
コリメータは小さい孔を多数あけた鉛板。検出感度を下げる。
lead plate having many small holes.
The collimator reduces the sensitivity of radioactivity detection.
Conventional gamma camera
Photomultiplier(PMT)

Scintillator
Collimator

Gammarays
Human body

PET camera

Currently, most PET is three-dimensional (3D) collection.

Good images can be acquired in a short time comparedto two-dimensional (2D) acquisition (The whole body(head to thigh) is collected in about 15 to 20 minutes).
But, it is easy to collect Compton scattered radiation,and the accuracy of quantification decreases.

2D
acquisition

3D
acquisitionDifficulty quantifying radioactivity distribution in the bodywith conventional camera
Attenuation of radioactivity Do in the body into D

Do : True radioactivity (Bq)
D : Measured radioactivity (Bq)
μ : Linear attenuation coefficient (cm-1)

Scintillation
cameraPET performs absorption correction on CT images,
so it is highly quantitative.

Rt. Lung cancer with metastases.
CT image
μ (x,y,z)Superimposed
image ofPET on CT

PET imageDo (x,y,z)

PET image (Do) is generated using CT image (μ).

CT value （ HU : Hounsfield Unit ）Value proportional to tissue density
The value based on the pixel value of the CT tomogramis the linear attenuation coefficient μt of each tissue inthe body, but a value proportional to μt is used for the
pixel value of CT to facilitate clinical understanding.

CT value = 1000 x （ μｔ - μw ） ／ μw
μw : X-ray absorption coefficient in the water
μt : X-ray absorption coefficient in the tissue

CT value in the air is -1000
1000 x （ μ air - μw ） ／ μw = -1000 （HU）
Strictly, the linear attenuation coefficient μair is not 0.
But it is extremely small compared to water or bodytissue, when calculating the CT value, μair = 0.

CT Value in the water is 0 (HU).
( Density of specific gravity 1 is 0 (HU) )1000 x （ μw - μw ） ／ μw = 0 （HU）
The CT value of a substance with a linear
attenuation coefficient twice that of water is 1000.
Double density of water is 1000 (HU). ( Tooth etc. )1000 x （ 2 μw - μw ） ／ μw = 1000 （HU）

Take home message
ｃｈｔｇｋａｔｏ．ｃｏｍ
Detailed nuclear medicine
equipment principles,
CT tomographic image
creation principle,
Slides explaining
quantitative analysis theory
such as cerebral blood flow,
Image analysis programs.
Please refer to those whoare interested.

Positron emitting nuclides used in PET

Produced in a cyclotron in a hospital.
Half-life

Synthetic radiopharmaceutical
min.

min.
min.

11C-Acetate

11C-Methioninemin.
Half-life of radioisotopes used in conventional Nuclear medicine studies
99m-Tc6 hours (時間)67Ga

78 hours (時間) （3.2 days 日）

201Tl

73 hours (時間) (3.0 days 日）A Cyclotron in
Hokkaido University
hospital.
Huge electromagnet.
Accelerates
hydrogen or
deuterium nuclei
and collides withelements to create
positron emitting
nuclides.

被曝 Exposure unit
Absorbed dose : 1 Gy (gray) is the exposure of a
1 kg object absorbing 1 J of radiation energy.
Dose equivalent：The exposure to which thehuman body receives 1 J of energy per 1 kg ofbody weight is 1 Sv.
Dose equivalent (Sv) = Absorbed dose (Gy) x Quality factor

Quality factor Ｑ : An index that indicates the energy
applied to the human body (the degree of ionization)
due to differences in radiation quality.
Ｑ＝１ : Ｘ-rays、γ-rays、β-rays
Ｑ＝１０ : Proton beam、neutron beam
Ｑ＝２０ : Multiple charged particles

Due to the short half-life of positron emitting
nuclides, exposure to PET scans is low.
The unit of exposure is Sv (mSv = 0.001Sv).
Exposure to receive 1J of energy per 1kg of bodyweight is 1Sv. Generally, 100mSv or less is harmless.
18F-FDG(185MBq) ４ ｍＳｖ (Bladder 20 Heart 10 Fetus 3)

11C-Methionine (370MBq)
15O-CO2( 3000MBq)

ＣＴ
Angiography

２ ｍＳｖ (Pancreas, Liver 7 )２ ｍＳｖ( Lung 11 ）７mSv ～ 10 ～7 mSv ～ 10 (Skin in 1 minute 0.5)

Stomach, digestive tract X-ray imaging 3 mSv

X-ray photography ０.１ mSv (Chest) ０.２ mSv（Pelvis)

１５Ｏ-ＣＯ２、Ｏ２

Brain PＥＴ quantifies CBF, OEF.
Cerebral Blood Flow (CBF), Oxygen Extraction Fraction (OEF)。
Case of severe stenosis in the right internal carotid artery.
Although it is not a cerebral infarction (MRI T2 image is normal),severe hypoperfusion, increased oxygen uptake in the Rt. brain.
It is called misery perfusion. (Immediately before infarction )１８Ｆ-ＦＤＧ

Brain ＰＥＴ Quantify brain glucose consumption.
Alzheimer's disease
Degeneration of bilateral parietal and temporal lobes,
decreased glucose metabolism.

Quantitative analysis of dynamic FDG PET
with three-compartment model

0.42 is a Lumped constant, uptake ratio of FDG compared with Glucose.

3-compartment model analysis enables to calculate
rate constant images of K1 , k2, k3 and k4 fromdynamic FDG PET image and arterial blood sampling.
K1 image shows uptate rate of FDG into both stroma
and nerve tissues.
k2 images show release
rate of FDG from stroma
tissues.
Stroma tissues do notneed Glucose, high k2
value is shown.

K3 images presents
uptake rate of Glucose
into the nerve tissues.
Nerve tissues need
Glucose, high k3 value isshown in the brain.

Dynamic brain FDG PET is performed for one hour,time-activity curve X(t) is acquired in every part ofthe brain.
3-compartment model analysis enables to divide
the X1 curve into the 2 time-activity curves, Xe(t)(stroma tissue curve) and Xm(t) (brain tissue curve).
This technique enables to analyze several
pathological uptake rate of brain nerve tissues.

Compartment model analysis is very useful toanalyze quantitative evaluation of several diseases.
But it sometimes requires arterial blood sampling
during the dynamic PET acquisition.
It is invasive and expose high radiation to the doctor
who is sampling blood, because he must be nearby
a patient who is emitting gamma rays from the body.

Recently, Deep-Learning is used in the clinical study.
Several cases of 18F-FDG dynamic brain PET data andtime-activity curves of sampled arterial plasma wereused as training data.
Then, the trained Deep-Learning algorithm could
estimate the time-activity curve of arterial plasma.
It enables non-invasive compartment model analysis.

Patlak plot is a 3-compartment model analysis
without arterial blood sampling.
This method isused clinically inthe 99mTc-ECD
brain dynamic
scintigraphy toestimate bloodflow in thebilateral cerebral
hemisphere.
Simplified modelis used, k4 isassumed to bezero, formula ofPatlak plot isderived.

Cp(t) is a time-activity curve of the arterial plasma.
But clinically, in the 99mTc-ECD dynamic brain scintigraphy,
the Cp(t) is used the time-activity curve of the Aortic arch.
X(t) is time-activity curve of the bilateral cerebral hemisphere.
Distribution of ∑Cp(t) / Cp(t) and X(t) / Cp(t) are plotted,
a fitted line is drawn.
The slope of the line is
Ki （= K1・k3/(k2+k3) ）.
Ki means the uptake
rate of 99mTc-ECD into
the cerebral hemisphere,
the value is used as
the cerebral blood flow.

１５Ｏ-ＣＯ２、Ｏ２

Brain PＥＴ quantifies CBF, OEF.
Cerebral Blood Flow (CBF), Oxygen Extraction Fraction (OEF)。
Case of severe stenosis in the right internal carotid artery.
Although it is not a cerebral infarction (MRI T2 image is normal),severe hypoperfusion, increased oxygen uptake in the Rt. brain.
It is called misery perfusion. (Immediately before infarction )Fick’s principle

PET study using 15O-CO2 or 15O-H2O, Fick’s principle
is used to estimate the tissue blood flow.
A micro-tissue uptakes Ct(t) of radioactivity during
one second, and radioactivity of the artery and vein
nearby the tissue are Ca(t) and Cv(t),the relationship of Ct, Ca, Cv and blood flow of the
micro-tissue f is presented as follows;d Ct / dt = f（Ca - Cv）

But it is impossible to measure the radioactivityof the vein nearby the micro-tissue Cv(t).
Anatomically, the volume of venous blood is muchlager than that of arterial blood in the micro-tissue.

So, radioactivity of the venous blood Cv and nearby
microtissue Ct have a linear relationship.
Then the ratio of the Ct and Cv is defined the value p（ partition coefficient （= Ct / Cv））. （ Cv = Ct / p ）.
The Fick’s principle is presented as follows;d Ct（ｔ） / dt = f Ca（t） - （ｆ / p）Ct（ｔ）

This equation enables to estimate the tissue bloodflow f , when Ca(t) and Ct(t) were acquired using
dynamic PET study.

Myocardial PET study with
15O-H2O, which enables toestimate regional myocardial
blood flow (MBF) using Fick’s
principle.
In the heart study, radioactivity of the artery is derived
from the Left ventricular count,blood sampling is not needed.

This case shows normal MBF
at resting state, but decreased
MBF at the LAD region atstressed state (ATP infusion).
Effort Angina at LAD region
is diagnosed quantitatively.

2-compartment model analysis is also useful.
It is used clinically for the 123I-IMP Brain SPECT,
myocardial dynamic PET with 11C-acetate, 13NH3, 82Rb.
123I-IMP Brain SPECT

IMP is amphetamine, stimulant, highly accumulated
into the brain nerve tissue. In the 2-compartment
model, k2 (return rate from the brain to the blood) of
IMP is assumed to be zero.

When the k2 value is zero, 2-compartment model toestimate cerebral blood flow (CBF) is solved easily.

123I-IMP Brain SPECT image is started to scan 20minutes after

injection of 123I-IMP, acquisition time is 20mimutes. So,123I-IMP
Brain SPECT is assumed to be scanned 30min. after injection.

Q.１

18F-FDG PET ?
Which is correct about SUV of 18

1. High blood sugar increases in tumors
2. Lower in muscles after exercise
3. Leakage of injection increases in the brain

4. One hour after administration, it becomes
constant in the tumor
5. It becomes 1 when 18F-FDG is evenly distributedin the body.

Q.2

Which lesion has low 18F-FDG accumulation ?
1. Colorectal cancer
2. Malignant melanoma
3. Malignant lymphoma
4. Head and neck squamous cell carcinoma

5. Well-differentiated hepatocellular carcinoma

Q.３

Choose two values to calculate SUV of 18F-FDG PET.
1. Weight
2. Blood glucose level

3. Radioactivity in blood
4. Volume of drug administered
5. Radioactivity of administered drug

Q.４

In the healthy person, which organ has less 18F-FDG
accumulation?

1. Brain

2. Liver4. Kidney

5. Colon

3. Gall bladderReferences