Prof. Dr. Çetin ÖNSEL CTF Nükleer Tıp Anabilim Dalı
What is Nuclear Medicine? Nuclear Medicine is the branch of medicine concerned with the use of radionuclides in the study and the diagnosis of diseases. The radionuclides are used for the assessment of organ function, the detection of disease, the treatment of some diseases and the monitoring of the effects of treatment.
Theimportanceof Nuclear Medicine (1) It provides physiological information not available from other imaging modalities diagnostic information of pathological processes before the outset of structural changes in an organ It uses very small amounts of radioactive material (radiopharmaceutical) that is introduced into the body and acts as a tracer
Theimportanceof Nuclear Medicine (2) Information obtained using nuclear medicine techniques is more comprehensive than other imaging procedures because it demonstrates organ function not just structure The result is that many diseases and cancers may be diagnosed much earlier
(nuclear pharmacy) What is radiopharmacy? It is a science which deals with the preparation and dispensing of radiopharmaceuticals (RFs) (radiolabel drugs) What are RFs? RFs are drugs that contain one or more atoms and are used for diagnosis and treatment
Nuclear medicine vs. other modality γ rays are used for imaging β rays are used for therapy in nuclear medicine Nuclear medicine shows the functions of the organs and less anatomic information Computed tomography, magnetic resonance, ultrasonography and plain films show the anatomy of the organs and less of the functions
A gamma camera
A PET/CT scanner
Normal and abnormal perfusion SPECT
Lung cancer: before and after therapy This is a 47 year-old female with non small cell lung carcinoma undergoing evaluation for the presence of mediastinal, hilar, or additional metastatic foci. Comparison is made with an outside CT scan of the chest which demonstrates a large spiculated mass measuring 4.5cm x 3.5cm in the left upper lobe as well as a smaller mass in the mid to lateral aspect of the right upper lobe measuring 2.2cm x 1.5cm. Interval resolution of areas of intense uptake in the left apex and right upper lobe. These findings are consistent with a marked response to interval therapies. 2. No evidence of residual or recurrent neoplastic disease is seen.
Characteristics of RPs The mass amount administered is low No intrinsic pharmacological effect For diagnostic use No disturb physiologic parameter For therapeutic use Radiation produced the desired therapy
Characteristics of RPs Two forms of RPs 1. Radionuclides (I-131, Xe 133...) Defines the bio-distributions 2. Combinations of the radionuclide (provides a detectable signal) and a ligand (chemical compounds) determines the bio-distributions (Tc-99m DTPA, Tc-99m MAA)
The kind of RPs Diagnostic RPs Therapeutic RPS
Diagnostic RPs Physical properties For physical properties of the radionuclide must be considered 1. Physical half life 2. Decay mode 3. Emitted photon energies 4. Availability
Physical properties Physical half life The half life is the time required to reach ½ of undecayed atoms at 0 time (Tc-99m 6 hours, I-131 8 day) Too-long lived RF: unnecessary body irradiation occurs
Physical properties Decay mode Imaging procedures require an electromagnetic photon (x or γ ray) The emitted photon must be high abundance and be monoenergetic β and α rays are not detected For diagnostic use a pure γ emitting decay mode would be desirable
Physical properties Photon energy The sensitivity and the resolution of the gamma camera system depends on photon energy The energy must be high enough that it escapes the body without being attenuated and must be also low enough to detect by the crystal The gamma camera electronics detect radiation in the 60-400keV The ideal energy should be in the range of 100-200keV
Physical properties Availability The most readily available radionuclide is Tc-99m pertechnetate Tc-99m is eluted from a Mo-99/Tc-99m generator The parent Mo-99m decays with a half life of 66 hours resulting in a shorter lived (6 hours) daughter (Tc-99m) A new generator is purchased once a week and supplies all the Tc-99m needed for that week
Biological properties The ideal RP should do the following Localize rapidly and exclusively in the organ of interest Localize more in pathologic tissue Be metabolically and pharmacologically inert Have no side effects Clear rapidly from background tissue Be rapidly excreted after the study is completed
Biological properties Mechanism of localization Functional Passive transfer (diffusion) Tc-99m DTPA Active transport or uptake (I-131 in thyroid Metabolic trapping (F-18 FDG) Receptor binding (In-111 pentetreotide) Antibody binding (Tc- 99m arcitumomab)
Biological properties Mechanism of localization Mechanical Capillary blockage (Tc- 99m MAA) Phagocytosis (Tc-99m sulfur colloid) Sequestration (heat denatured Tc-99m RBCs for spleen Compartmental space localization (In-111 DTPA for CSF flow Abnormal extravasations (Tc-99m IDA in bile leaks)
Biological properties Route of administration The route of administration often determine the localization characteristic of RFs Lung ventilation can be studied by inhalation an aerosol or gas Pulmonary perfusion is studied by iv injection of Tc-99m MAA Different biodistributions and kinetics can be obtain by selecting the route of administration IV injection of Tc-99m Sulfur Colloids concentrates in liver, subcutaneous injection is cleared by lymphatics
Biological properties Target uptake The RF with a better uptake is a superior imaging agent The rate of uptake is also important The thyroid can be imaged at 20 min with Tc-99m pertechnetate, but 4-6 hours with I-123 NaI
Biological properties RF excretion The RF must clear from blood and background tissue to achieve high contrast The major excretion routes are Kidneys (glomerular filtrations) GI tract Hepatobiliary route
Chemical properties Ease of preparation and availability Tc-99m-based RFs from ready to use commercial reagent kits Stability and expiration The best Tc-99m kit formulation give products that are stable at least 6 hours after preparation Stabilized bone scan kits are preferable to non stabilized kits
Therapeutic RPs (1) In 1911, Radium-226 was used to treat lupus In 1939, phosphor 32 was used to treat leukemia In 1942, Sr 89 was used to treat metastatic bone lesions in prostate cancer In 1942, I-131 was used to treat thyroid cancer
Therapeutic RPs (2) Advantages over chemotherapy and external beam irradiation No pharmacological and side effects RP therapy exposes neighboring malignant cells to lethal irradiation even the nuclide is not bound to them RP therapy is selective; high target to non-target ratio can be achieved RP therapy delivers a hyper fractionated dose compared to external beam irradiation
Therapeutic RPs Nuclear properties Half-life The half life must be long enough to localize in diseased cells and clear from normal cells Decay mode Particulate radiation with high energy transfer is desirable for maximum exposure and damage to tissue Beta emitter( I-131, P-32, Sr-89) The ranges in the tissue are in millimeters Alfa and auger emitters are being investigated The ranges in the tissue are in micrometers
Therapeutic RPs Biological properties Rapid blood clearance Good tumor localization Long residence time Non-tumor RP quickly excreted
Therapeutic RPs Metabolism and excretion Therapeutic RPs should not undergo any metabolism A faster rate of excretion reduces blood levels, and whole body and bone marrow exposure
Production of RFs Radionuclides used in medicine artificially produced (by bombarding a stable nucleus with subatomic particles (e.g.,neutrons, protons) Reactor (Xe-133, I-131, P-32, Mo-99) Cyclotron (C-11, N-13, O-15, F-18, I-123) Generator (parents produced reactor or cyclotron)
Mo-99m/Tc99m generator Cost effective, safe and simple to use Tc-99m produces numerous useful RPs Parent half-life of 66 hours allowing weekly delivery This generator consist of a small glass of alumina column that the parent (mo-99) is strongly adsorbed to and the daughters have a lesser affinity While the column Mo-99 decays to Tc-99m TcO 4 Consequently TcO 4 exchange with chloride in the saline elute so Tc-99m Na TcO 4 is readily eluted while MoO 2-4 remains attached to the column
Tc-99m pertechnetate Tc-99m pertechnetate Energy 140 kev Half life 6 hours Biodistribution After İV injection pertechnetate is removed from the interstitial fluid by the stomach, salivary glands, thyroid, bowel, choroid plexus, sweat glands and kidney
Non-Tc-99m RFs Agent Half-life Energy Tl-201 73 hours 69-80 kev Ga-67 78 hours 91-400 kev I-131 8 days 364 kev Cr-51 27.7 days 0.320 MeV In-111 67 hours 173-274 kev
Quality control of RFs (I) Physicochemical tests Physical characteristics(solution contain no particulate matter) ph should be 7.4 Radionuclide purity (any contamination can be identified) Radiochemical purity (e.g., free Tc-99m and labeled Tc99m chromotography) Chemical purity ( the fraction of the material in the desired form) Biological test Sterility indicates the absence of any viable bacteria of microorganism in a RF preparation Pyrogenity All RFs for human administration are require to be pyrogen free Toxicity Acute and chronic effects and safe dosage levels must first be established before approval for human use