CONCISE MANUAL OF NUCLEAR MEDICINE

FOR MEDICAL STIDENTS

EDITED BY PROF.DR.I.KOSTADINOVA

SOFIA, 2010

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 NM1. 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 In vivo In vitro 131 I- treatmentImaging 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 NMRadioisotope / 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

99mTc -produced from generator comprises 90% of the diagnostic activity of NM-Department. The rest is due to 131 I, 51Cr, 201 Tl. 99mTc is a pure gamma emitter, E=140 keV, T1/2-6h. Unit of radioactivityBq-one disintegration per second. MBq=106 Bq. 37MBq=1mCiRPh- any chemical compound containing radionuclide, administered to a patient for diagnosis or therapyGamma camera-=Scintillation camera - imaging device with sodium iodine crystal for detecting gamma-emitting radionuclidesScintilation- the process by which ionizing radiation is converted to visible photonesStatic Image=Scintigram-Procedure to produce and record an image of the distribution of radionuclide in a patient's specific organ, using a gamma cameraDynamic imaging- Acquisition of sequential time dependent scintigrams to determine function and structure of the organSPECT-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 organsPET- 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.

INSTRUMENTATION IN NUCLEAR MEDICINE Conventional Gamma camera / single or double head / for a functional

scintigraphic visualization

Hybrid imaging- for both functional / scintigraphic / and morphologic / CT / imaging

- SPECT/CT –using gamma RPh PET/CT – using positron RPh

Advantages of hybrid imaging

• 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

• A precise localization of the pathological changes is possible and absolutely necessary for surgery and radiotherapy

Differences between SPECT/CT and PET/CT

• They use different emitters: SPECT-only gamma emitted radioisotopes and PET-positron emitted.

• Most often used isotopes for SPECT are 99mTc and 131I and for PET- 18F and 11C.

• The most common use of CT in both techniques is for a higher quality and a higher specificity of the scintigraphic image because of the attenuation correction of the attenuated gamma rays and a possibility for a precise localization.

• Final result is a higher diagnostic accuracy.

Hybrid images

PET/CT in a patient with Ca ovarii SPECT/CT in a patient with bone meta

NUCLEAR MEDICINE IN ENDOCRINOLOGYI.Thyroid1.Thyroid Scintigraphy- Principle- RPh / 99mTc, 131 I, 123 I / is selectively captured in the thyroid in

accordance with the funtional and morphological status- Indications-in differentiation of the thyroid nodules, to elucidate the reasons for

tyreotoxicosis, thyroidites, evaluation of goitres, retrosternal masses and the effect of therapy.

- 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

“Cold” nodule of thyroid “Hot” nodule of thyroid

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 testIt 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 recurrence5.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.

A Patient with differentiated thyroid carcinoma and treatment with 131Ia/ before therapy b/ after therapy

II. Parathyroid scintigraphy

It is applied pre-surgically to localized parathyroid, which are hyperfunctioning/ according to the level of parathyroid hormone /.Normal parathyroid glands are not visible on the scans. Imaging is carried out using subtraction scan technique. Initially 99mTc-pertechnetate is injected to outline the thyroid, then 99mTc-MIBI to outline thyroid plus parathyroid. А subtraction is perform to visualize parathyroid tissue / adenomas which size is more than 300mg /

III. Adrenal glands

1. Scintigraphy of adrenal cortex - it is a test of adrenal function and localization of tumor, after a biochemical diagnosis has been made. Physical enlargement of an adrenal is readily determined by CT, but such enlargement is commonly

difficult to evaluate functionally. Scintigraphy with 131I - cholesterol is performed in:

- adrenal hyperplasia / Cushing's Syndrom-bilateral uptake / - in adenoma / unilateral uptake/- carcinoma-usually no uptake2. Scintigraphy of adrenal medulla - with 131I-MIBG. It is useful for localization of phaemochromocytomas/ including metastases /, also neuroblastomas end paragangliomas. Higher activity is used for treatment.

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

- Metastatic disease – detection of meta from extraosseous primaries /prostate, breast, lung,etc./, detection of areas at risk for pathologic fractures, monitoring after therapy

- Primary bone tumors-the osseous involvement in scintigraphy is often more extensive than conventional radiogrphs, which could be due to relative hyperemia in the surrounding tissue.

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.

A patient with prostate cancer and multiple bone metastasis

IV. Joint disease-arthritic changes result in increased accumulation in the involved areas, which estimates the extend of disease seen in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis.

-Osteonecrosis involves interruption of blood supply to bone with resultant cellular death, associated with aseptic necrosis due to trauma, steroids, radiation, alcoholism, etc. In the early avascular phase there is decreased tracer accumulation and in the later stages-an increased tracer uptake is seen due to reparation and revascularization.- Joint prosthesis-BS is valuable in the early detection of infection and loosening of the prosthesis in patients who have undergone arthroplasty. Focal uptake may indicate loosening of the prosthesis, whereas a diffuse increase of the activity is more likely to indicate infection / could be proved by an additional leucocyte scintigraphy/

NUCLEAR MEDICINE IN CARDIOLOGYSeveral radionuclide techniques are used to study the heart- myocardial perfusion scintigraphy, radionuclide ventriculography and a new method-gated SPECT.

I. Myocardial perfusion scintigraphy

Uptake of the radiopharmaceutical / 99mTc-MIBI, 201 Tl / is proportional to the blood flow and in this way it displays myocardial vitality. If there is disturbance in the blood supply or myocardial cells are damaged, then an abnormality is seen on the image. Coronary deficiency is detected by comparing exercise and rest images. - In reversible myocardial ischaemia / stenocardia / there is a hypoperfusion / decreased uptake of RPh / is seen in exercise, while rest images are normal. - In non-reversible ischaemia /myocardial scar/ decreased uptake of RPh is seen in

both exercise and rest images.

Indications are to assess:- atypical chest pain- investigation of myocardial vitality- differentiation of reversible from non-reversible ischaemia- in cardiomyopathy- pre- and post-CABG surgery and early diagnosis of restenosis

The accuracy of the scintigraphy / 90% / is higher than ECG and especially if SPECT technique is applied.

A patient with a combination of reversible and non-reversible myocardial ischaemia

II. Radionuclide ventriculography

It is performed to assess myocardial kinetics and ventricular function. 99mTc-labelled erythrocytes are used. Serial scintigrams are performed, from endsystole to enddiastole, in synchronization with ECG.The left ventricular ejection fraction is a useful index of ventricular function and normally is 64+/- 8%.Indications are abnormalities of ventricular movements: conduction disturbances, hypokinesia, aneurysm, following the effect of treatment.III. Gated SPECT 99mTc-MIBI is used and it gives a complex information - for myocardial perfusion, kinetics, ejection fraction / global and regional /, and as a final result-for myocardial viability.IV. PET scintigraphy gives data for myocardial perfusion and metabolism.Positron emitters are used-18Fl-FDG, 13N, 15O,11C. It is the most accurate method among all visualized ones to reflect myocardial viability and the effect of revascularization / bypass surgery /.V. Intracoronary radionuclide therapyIt is well known that the frequency of coronary restenosis after revascularization is very high-up to 40%. If a beta emitter is installed in the coronary graft /90Y, 188Re/this frequency can be reduced to 20%.

LUNGS SCINTIGRAPHYIt gives information for the perfusion / blood supply / and ventilation.I. Perfusion scintigraphyPrinciple-after injection of 99mTc-macroagregates of human serum albumin /MAA/, it loges into the terminal arteriolo-capillary bed in proportion to the regional blood flow. Reduced activity in the lung image indicates reduced perfusion, which may be due to pulmonary embolism /PE/, but also to chronic obstructive airways disease, pneumonia, tumor or pleural effusion. Normal lung scintigraphy rules out /PE/ in 100%, but typical picture is reduced or absent uptake in 2 or more segments. To avoid making a positive diagnosis of PE, ventilation imaging in addition is helpful. In PE, ventilation remains normal, whereas perfusion is impaired, unlike other diseases.

Normal perfusion scintigraphy of the lung A patient with pulmonary embolism

II. Ventilation scintigraphyMost often 99mTc-technegas or 133Xe as a gaseous inhalating agents is used. Images record regional ventilation of the lungs. Mismatched defects with perfusion / perfusion defects with normal ventilation / characterize PE. III. Radionuclide diagnosis of lung tumorsTumor seeking agents like 67Ga or 99mTc-MIBI are logged in tumors and their metastases and recurrences. This diagnostics is used, when for the other visualized methods, it is difficult to differentiate vital tumor from scar.

RADIONUCLIDE LABELLED BLOOD CELLS

Using radionuclide methods, blood cells-erythrocytes, leukocytes, platelets are labeled with application in hematology, internal medicine, surgery.І. Red blood cells 1.Erytrokinetics-it can be used for following the processes of distribution, rate and site of destruction and red cell survival, using "in vitro" labeled erythrocytes with 51Cr-sodium chromate. Indication: - In hemolytic anemia for determining the localization of destruction of red cells. If the spleen is a site of destruction, a splenectomy is proposed and appropriate treatment effect is achieved.-In cases with unclear anemia for elucidating their pathogenesis and as a result - to undertake the optimal treatment2.Blood volume determination, using 51Cr-sodium chromate.Its measurement is helpful for proof the diagnosis of true polycythaemia, where red cell volume is increased and plasma volume is normal or decreased. It could be differentiated from relative polycythaemia, where red cell volume is normal, but plasma volume is decreased and from secondary polycythaemia, where plasma volume is increased.3.Labeled red blood cells are also used for localization of hemorrhage in the abdomen and for radionuclide ventriculography.

II. Labeled leucocytes with 99mTc-HMPAO or 99mTc-monoclonal antigranulocyte's antibodiesRadionuuclide imaging is useful to detect active foci of infection, when there are no obvious localizing signs and ultrasound and CT are often unhelpful. The advantage of the method is that it is very specific and can search infection in the whole body, noninvasively. Another applications are patients with abdominal abscess /after surgery/, colonic inflammation / Croh'n disease, ulcerohaemorragic colitis / and osteomyelitis. III. Labeled platelets1. Thrombokinetics- following the processes of distribution, rate and site of

destruction and platelet survival, using "in vitro" labeled platelets with 11In-oxine or 51Cr-sodium chromate.

Indication: - In essential thrombocytopenia /Werlhoff disease / for determining the localization of destruction of platelets. If the spleen is a site of destruction, a splenectomy is proposed with appropriate treatment effect. - In cases with unclear thrombocytopenia for elucidating their pathogenesis and as a result - to undertake the optimal treatment2. For visualization of active thrombosis in the big vessels and in the heart. US can

detect all thrombosis-non active and active. The last are haemodinamically active and are responsible for brain and heart events.

Leucocyte scintigraphy in a a patient with active ulcerohaemorragic colitis

NUCLEAR MEDICINE IN GASTROENTEROLOGY

I. Liver and hepatobiliary imaging1. Liver scintigraphyRadionuclide imaging with 99mTc-sulfurcolloid provides a non-invasive method of examining size, shape, position and function and to a limited extend, the presence of localized lesions. It is used less frequently compared to ultrasound and CT for detecting the presence of cysts, metastases, abscesses and primary tumors in the liver. Diffuse liver disease and the presence or absence of splenic lesions can also be determined by this imaging. Relative enlargement of the left lobe and usually the spleen suggest diffuse liver disease. Localized lesions in the liver from 1-3 cm, depending on their site can be visualized as cold areas.2. Hepatobiliary imagingIt is carried out to follow the function of the hepatocytes / including liver transplant/and the patency of inta- end extrahepatic bile ducts. The main indication is acute cholecystitis although post surgical problems like bile leakage and biliary reflux can be identified. Visualization of the gall bladder is highly specific/ more than 95% / for excluding acute cholecystitis. Delayed excretion into the gut suggests hepatocellular disease, absent excretion to the gut with increased urinary excretion suggests complete surgical obstruction.

ІІ.Gastrointestinal bleedingRational: the injected RPh / 99mTc-colloid or 99mTc-red blood cells / is localized in the site of active bleeding. As little as 0.1 ml may be detected and the source localized, but if bleeding occurs during the time of investigation. This methods are 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 transitThe 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 refluxAfter 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. Indications-pain 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 glandsThe 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.

Normal dynamic kidney scintigraphyq visualizing structure and function of kidneys

Pathological renographic curves:- hydroneophrotic type - when there is a mechanical or functional obstacle for the

urine drenage / e.g. stones in pyelocalices /- nephrectomy type - when there is no kidney function- isostenuria type - in renal insufficiency Indications: All types of diffuse kidneys diseases, hypertension, suspicion of altered kidneys function

2. Static imaging / scintigraphy /99mTc-DMSA is used to image the renal parenchyma / tubular cells /. A lesion within the renal parenchima will show a "cold"area / tumor,cyst,abcessus, pyelonephritis/ .While many such lesions are better imaged by other means, e,g. US or CT, radionuclide imaging is particularly useful in the diagnosis of chronic pyelonephritis and scarring, detection of small residual amounts of renal tissue, abnormalities such as horseshoe and pelvic kidney.

3. Captopril renographyIt is used when unilateral renal artery stenosis is suspected. Boths Captopril / with 25mg Captopril given orally / renograophy and baseline study are performed. Captopril decreases the GFR of the stenotic kidney and a delay in the time to peak will be seen, compared with the other side.

4. Diuretic nepgrographyIt is performed to distinguish obstructive / in kidney stones or tumor / from non-obstructive hydrenephrosis / dilatation of the pelviocalical system of the kidney /. Usually it is performed at the end of the standard renogram by injection of Frusemide. Normally a prompt fall in the curve will be shown in response to the diuretic/ non-obstructive hydronephrosis /, while in obstructive hydronephrosis - the rising of the renogram curve contiues.

5. Renal transplant renographyRadionuclide studies are useful for non-invasive sequential monitoring of blood flow and functionq following renal transplantation. Acue tubular necrosis, vascular occlusion, rejection, ureteric obstruction and urinary extravasation can be identified.

6. Ureteric refluxIt may be demonstrated if the patient / child / micturates during the renographic study. This is much less invasive than the alternative radiological technique.

7. Testicular scintigraphyThe differentiation of causes of a painful testicle can be clinically difficult. Torsion requires prompt surgery, while orchiepididimites - antiinflammatory drug administration. Radionuclide flow and tissue phases of imaging following i.v. injection of 99mTc-pertechnetate will demonstrate reduced blood supply to torsion while in orchiepididimites increased activity is registered.

II. Non-imaging methods

1. Non-imaging nephrography-non invasive method for determination of kidneys function, using only renographic curves.It is performed on apparatus with two scintilation probes, using 131I-hippurate, which makes this method less expensive than dynamic renal scintigraphy / on gamma camera /, but it is also less accurate.Indications are the same, as dynamic renal scintigraphy.

3. Renal clearances determination- Tubular secretion / Effective renal plasma flow / can be assessed using 99mTc-MAG3 which investigation usually is combined with dynamic renal scintigraphy on gamma camera- Glomerular filtration rate can be assessed using 51Cr-EDTA. No urine collection

is required and the preparation is simple and more reliable than creatinine clearance, esp. in paediatrics.

4. Residual urine determination.The test is performed in patients with prostate hypertrophy. Normally less than 20ml residual urine is in bladder. In values more than 100 ml - surgery

/ e.g. prostatectomy / has to be performed in order to prevent acute renal insufficiency.

5. Therapeutic methods for a palliation of pain in bone matastases

Principle-the used RPh accumulate in the sites of bone metastases, corresponding to their perfusion and metabolism / metabolitic curitherapy /. This therapy is applied as a palliative treatment in patients with prostatic carcinoma, who have not responded to conventional therapy and in patients with breast, lungs, kidneys, bladder, etc. carcinoma / 32P, 89P, 186Re, 153Sm /. Confirmation of bony metastases by bone scanning is advised prior to therapy. 32P is rarely applied, as it induces myelosupression. Contraindications-in advanced leucopenia / Le bellow 2600/ and thrombocitipenia / Thr-bellow 60000 /.

Most applicable is 89Sr, whish is effective in up to 80% of the patients with a duration of the effect-about 6 months.Advantages:- one dose application during the whole therapeutic period- specific uptake in bone metastases- in 30% of the patients the appearance of new metastases can be delay or stop- no adverse effects, typical for narcotics, radiotherapy and chemotherapy- prolongation of life can be achieved

CENTRAL NERVOUS SYSTEM IMAGING

1. Imaging the integrity of blood-brain barrier

99mTc-DTPA is used less frequently nowadays compared with CT or MRI. It is based on the selective permeability of the blood-brain barrier, which excludes the radiopharmaceutical from normal brain tissue. In abnormal conditions, when there is a disturbance of the microcirculation in the brain, the blood-brain barrier is disturbed and the abnormality / subdural haematoma, tumor, abscess / is seen as increased activity. Sensitivity is 90%, but CT or MRI dive better resolution of details.

2. Perfusion brain scintigraphy Brain perfusion can be visualized, using 99mTc-HMPAO and tomographic gamma camera. It is reduced in dimentias / Alzheimer's disease, epilepsy, strokes and migreine / and the treatment effect can be monitored.

NUCLEAR ONCOLOGY

It uses RPh for diagnosis of tumors, its metastases and recurrences and to monitor the effect of treatment. It is the most active developing trend in nuclear medicine.

1. Using of conventional RPh.No perfect tumor specific RPh has been described yet, some however are more specific than others.- Non-specific RPh- they are used as a screening markers: 99mTc-MDP for bone

scintigraphy, 99mTc-macroagregated albumin for lung scintigraphy, 99mTc-colloid 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. RadioimmunoscintigraphyMonoclonal 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 scintigraphyUsing 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* + Ab125I 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-thyreoglobuline4. Vitamines-B125. Enzimes - gastrine6. Drugs-digoxine

Trends for developing of RIA are:1. More and more substances are measured using RIA2. Development of ultramicrometods, using less quantity of serum /below 0,1ml/ 3. Development of kits for measuring 2 substances at the same time4. Computarisation of the whole measurements