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MANUAL OF NUCLEAR
MEDICINE
Nuclear medicine / NM /
NM is the branch of medicine, in which radiopharmaceuticals / RPh / are used in
the diagnosis and treatment of diseases.
Its development depends on:
1. Introduction and application of more and more NM-methods for diagnosis of the
diseases of heart, lungs, brain, gastro-intestinal tract, kidneys, bones, endocrine
glands, tumors, inflammation and for treatment of tumors, their recurrences and
metastases, retractable synovites and some heamatological diseases.
2. Innovation of imaging NM technique - from conventional scanners and planner
gamma cameras to tomographic gamma cameras- SPECT / single photon
emission computer tomography / and PET / positron emission tomography /.
3. Introduction of new radiopharmaceuticals / RPh/ for an early diagnosis of
functional changes of the investigated organs, before appearance of structural
changes, which can be visualized with other imaging methods / rentgenology,
sonography, CT /.
Radionuclide techniques are diverse and generally non-invasive, safe with low
radiation burden, but it is necessary to consider whether a procedure offers the most
effective way of solving a particular diagnostic problem. The quality of achieved
diagnostic information, availability of equipment, radiation dose of the patient, the
cost and the possibility of using alternative imaging methods without radiation are
the most important factors for making a decision.
Principles of NM
1. RPh can be applied in the investigation of all organs and systems.
2. The basis for its usage is the specific accumulation of RPh / labeled with
radioisotope chemical substances/ in different organs.
3. For the functional and metabolitic evaluation of some organs the most important
factors are the speed, degree of uptake and elimination of RPh.
4. The results obtained are displayed as planar or tomographic scintigrames /
distrbution of the activity in the investigated organ /, curves / radiography / or
counts per min.
/ radiometry /.
Classification of NM procedures
Diagnostic
Therapeutic
131
In vivo
In vitro
I- treatment
Imaging
Non-imaging
RIA
- thyrotoxicosis
-planar
-uptake tests
-hormones
- Ca thyroid
-tomographic - renography
- Tu markers
Bone pain paliation
SPECT
- clearances
- enzymes
/ 89Sr,32P,188Re,153Sm /
PET
- blood volume - vitamins
Hematological disorders
-hybrid
- others
Neuroendocrine Tu
PET/CT and SPECT/CT
BASIC TERMS IN NM
Radioisotope / radionuclide / - atoms with an equal atomic number but different
mass number which produce radiation, when decay. All isotopes of the given
element have equal chemical and biological properties. Every radionuclide has the
following characteristics:
- type of radioactive decay-alfa, beta, gamma rays /electromagnetic radiation/
- energy, which it emits
- half time / T1/2 /- this is time. for which half of the radionuclide decays
99m
Tc -produced from generator comprises 90% of the diagnostic activity of NMDepartment. The rest is due to 131 I, 51Cr, 201 Tl. 99mTc is a pure gamma emitter,
E=140 keV, T1/2-6h.
Unit of radioactivity
Bq-one disintegration per second. MBq=106 Bq. 37MBq=1mCi
RPh- any chemical compound containing radionuclide, administered to a patient for
diagnosis or therapy
Gamma camera-=Scintillation camera - imaging device with sodium iodine crystal
for detecting gamma-emitting radionuclides
Scintilation- the process by which ionizing radiation is converted to visible photones
Static Image=Scintigram-Procedure to produce and record an image of the
distribution of radionuclide in a patient's specific organ, using a gamma camera
Dynamic imaging- Acquisition of sequential time dependent scintigrams to
determine function and structure of the organ
SPECT-single photon emission computed tomography - construction of three
dimensional images displayed as organ sections, using gamma rays emitted from the
radionuclide/ most often 99mTc-compounds /incorporated in the investigated organs
PET- positron emission tomography- construction of three dimensional images
displayed as organ sections, using positrons emitted from the radionuclide
/ 18Fl, 13N, 15O, 14C-compounds /incorporated in the investigated organ.
Gives complex information for the structure and function of the organs
Shortens the time for making diagnosis and consequently the initiation of
therapy
The scintigraphic images are with a higher quality because of a correction of
the attenuated gamma rays through CT
The thyroid nodules could be hot, cold or warm in accordance with the degree of
uptake of RPh in the nodule and in rest of the thyroid parenchyma
2.Thyroid uptake test- the used RPh / 99mTc, 131 I, 123 I / is captured in the thyroid
in accordance with the funtional state of the thyroid / hormonal production /. A
percent of thyroid uptake is calculated, compared with the standard / 100% / as a
quality index of the function of thyroid.
131 I, 123 I are used for the determination of the doses of activity, required for
treatment of thyreotoxicoses.
3.Perchlorate discharge test
It assesses organic binding of iodine by the thyroid and proves defect in synthesis
of the hormones/ in patients with hypothyreoidism / as a sequence of the
decreased or absent activity of the enzyme peroxidase.
4."In vitro" tests / without radiation burden for patient / for an evaluation of
thyroid function:
- TSH - very sensitive for assessing thyroid status. Low TSH suggests
Hyperthyroidism, high values-hypothyroidism
- T4, T3 and free hormones, which are more precise- FT4 , FT3
- Thyreoglobulin-it is useful in assessing patients with treated thyroid carcinoma
to assess the effect of treatment and to detect metastasis and recurrence
5.Suppressive thyroid scintigraphy / with addition of thyroxine before and during
Scintigraphy /. It is applied for assessment of some "hot" thyroid nodule-if it is
compensated or non-compensated / if the rest of the parenchyma is visualized or
not /
6.Whole body scintgraphy with 131I - to evaluate a patient with differentiated
thyroid carcinoma - looking for metastases, recurrence and to follow the effect of
therapy. The whole evaluation of the patient comprises history, clinical check up,
lung X-ray, serum level of thyreoglogulin.
2.
BONE SCINTIGRAPHY / BS /
- It is the most requested isotope study in NM, because of the high sensitivity for
lesion detection and the posibility to survey the whole body.
- It is applied in oncology, orthopedics, rheumathology and endocrinology
- BS is a functional test of bone metabolism that complements the anatomical details
from the other imaging methods and displays pathological changes earlear than
structural changes occur.
- 99mTc-MDP is most often used and reflects osteoblastic activity and skeletal
vascularity.
- It has a lower specificity as many conditions demonstrate increased tracer
accumulation-malignant and benign tumors, infections, trauma, metabolic
disorders, but in most of them typical pattern is recognized, which suggest a specific
diagnosis.
- Standart protocol for bone scintigraphy includes imaging 2-4 h p.i.
- Dynamic scintigraphy / 3 phase bone scan / permits evaluation of the vascular,
blood pool and osseous phases.
Indications
I.Tumors
-
II. Infection-3-phase bone scintigraphy is very useful, as early phases reflect the
hyperemia and the delayed images-the extend of reactive bone formation
III. Trauma-the uptake of tracer steadily increases with time due to increased
vascularity and bone turnover in the fracture-within 72h all of them are
demonstrable.
- Stress fractures-result from repetitive, prolonged muscular action on the bone
that is unaccutomed to such stress.BS is highly sensitive to the early detection of
stress-related bone and tendinous injuries, where radiographs are often negative.
non-invasive, but a disadvantage is that they provide less anatomical details than
endoscopic methods.
Ectopic gastric mucosa in Meckel's diverticulum can be detected, following an
injection of 99mTc. The investigation has no analog among the other imaging
methods and its accuracy is very high / about 90% /.
III. Oesophageal scintigraphy
1. Visualization of oesophageal transit
The passage of the radioactive bolus / 99mTc-colloid / through the oesophagus is
followed from the mouth to the stomach. The speed / transit time / and the way of
transit is visualized for an exclusion of local retention. Indication-pain in the region
of oesophagus and ahalasia.
2. Visualization of oesophageal reflux
After intake of the radioactivity, serial images of its passage are taken. Regions of
interests from the oesophagus and stomach are taken. There is a reflux, when more
than 4% of radioactivity of the stomach is registered in the oesophagus. Indicationspain in the region of oesophagus and suspicion of pulmonary aspiration of gastric
contents in adults and infants / aspiration pneumonia /.
III.
Stomach scintigraphy
Gastric emptying studies are helpful in elucidating post gastrectomy problems due
to rapid emptying e.g.dumping syndrome and also slow emting e.g.diabetic
gastroparesis. Solid and liquid studies / with radioactive labeled liquid and solid
substances / may be carried out. Liquid emptying is more rapid than solid one.
V. Salivary glands
The parotid and submandibular glands can be imaged using 99mTc-pertechnetate.
Uptake by the glands is calculated on the computer with a stimulation of excretion
with lemon juice. This excretion is normally visible on the computer graphs. If there
is obstruction, then the emptying curve is normal. In Sjogren's syndrom, uptake is
reduced and excretion is not detected.
RADIONUCLIDE METHODS IN NEPHROLOGY AND UROLOGY
I. Imaging methods
1. Dynamic renal scintigraphy-after i.v. application of RPh / 99mTc-MAG3,
99mTc-EC /, consecutive images of kidneys are acquired, which reflect perfusion,
function, size, position and structure of each kidney. Renographic curves are ploted
after delineating the "ROI" over kidneys and background. Normally a renogram
curve rises to a maximum at 3-5 min. / Tmax./ and declines to less than half
maximum / T1/2 / by 16 min. Uptake of each kidney between 1-2 min. is a useful
indication of the relative function of each kidney / normally 45-55% / of total.
Non-specific RPh- they are used as a screening markers: 99mTc-MDP for bone
scintigraphy, 99mTc-macroagregated albumin for lung scintigraphy, 99mTccolloid for bone marrow and liver scintigraphy, 99mTc-DMSA for kidney
scintigraphy, 99mTc-pertechnetate for thyroid scintigraphy. The tumor is
visualized as a "cold" lesion.
- Tumor seeking RPh: 99mTc-MIBI, 67Ga-citrate, 201Tl for bone, thyroid, brain ,
lymphoma, breast, lung's scintigraphy. The tumor is visualized as a "hot"lesion
and radioactivity decreases with regression of the disease / favorable effect of
therapy /
- Specific RPh- it specifically accumulates in only one tumor - e.g.131 I in thyroid
carcinoma and metastasis.
2. Radioimmunoscintigraphy
Monoclonal antibodies to various tumor constituents can be labeled antibodies
l;abeled and used for imaging primary and metastatic sites and have potential for
therapy /radioimmunotherapy/. Useful results have been obtained in gastrointestinal
and ovarian tumors and melanoma, mostly used labeled antibodies labeled with
131I, 123I or 111In.
3. PET scintigraphy
Using metabolic markers such as 18Fl-FDG, 15O, 11C, 14N, an image of the tumor,
its metastases and recurrence can be visualized, based on their higher metabolic
activity / increased perfusion, O2, glucose than the normal tissue /.
RADIOIMMUNOANALYSIS / RIA /
These methods belong to non-imaging methods "in vitro". Using them, the level of
different biologically active substances, usually in serum were determined, without
any radioactive burden to the patient.
Berson and Yallow measured the quantity of insuline in the blood of a patient with
diabetes and they were awarded with the Nobel prize for a medicine in 1977.
Nowadays about 200 substances can be measured due to existence of the ready made
kits, produced from different firms. The concentrations of antigens / substances
which has to be determined / most often are in the range of nanograms / 10-9 g / or
picograms / 10-12g /. Bigger concentrations are measured with the methods of
biochemistry and immunology.
Basis for RIA is the reaction Antigen /Ag/- Antibody / Ab /, which intensity depends
on the concentration of the substances, which is measured, using radioactive
indicator. The principle is as follows: competition between non-labeled Ag / the
substance from the patient, which has to be measured /and labeled Ag /from the kit /
for not enough quantity of the Ab. One radioimmune kit consists from Ab; labeled
Ag and standarts / non-labeled Ag, which concentration is known /. The reaction
runs as follows:
Ag + Ag* + Ab
125I is most often used radionuclide for labeling of Ag. Usually 0,1-0,2 ml serum are
enough for the measurement of biologically active substances, which could be:
1. Hormons of the thyroid, ovaries, suprarinals, hypophysis, pancreas, e.g. T3, T4,
TTH, estradiol, prolactine, cortisol, insuline.
2. Tumor markers- these are highly specific antigens for the diagnosis of tumors,
their metastases and recurences and for monitoring the effect of treatment- PSA,
CA15-3, CA125, etc.
3. Plasma proteins-thyreoglobuline
4. Vitamines-B12
5. Enzimes - gastrine
6. Drugs-digoxine
Trends for developing of RIA are:
1. More and more substances are measured using RIA
2. Development of ultramicrometods, using less quantity of serum /below 0,1ml/
3. Development of kits for measuring 2 substances at the same time
4. Computarisation of the whole measurements