MCCCD Official Course Competencies:

DMI276  2003 Fall – 2009 Summer II

Nuclear Medicine Theory III

1.

Define commonly used terms in the field of nuclear medicine. (I)

2.

Perform calculations used in the nuclear medicine field including the conversion of units of measure, specific activity and specific concentration, and effective half-life. (I)

3.

Describe the components and properties of diagnostic and therapeutic radiopharmaceuticals, the function of each component, and the desirable characteristics for each. (I)

4.

Discuss the factors considered when selecting a radionuclide or pharmaceutical to produce radiopharmaceuticals for diagnostic and therapeutic procedures. (I)

5.

Discuss radiation protection and regulations related to radiopharmaceuticals at the federal and state level to include Nuclear Regulatory Commission (NRC) requirements for storage and control of licensed radioactive materials, quality control program when therapeutic radiopharmaceuticals are used, possession and quality control of dose calibrators, permissible Mo99 concentration in generator eluate, use and labeling of syringe and vial shields, storage and dispensing of radioactive volatiles, gases and aerosols, pr

6.

Discuss sources of radiation exposure, shielding methods and precautions, and the various methods of disposal of radioactive materials. (II)

7.

Differentiate between restricted and unrestricted areas including restrictions that apply and the indications and use of required signs. (II)

8.

Differentiate between recordable and reportable events ant the actions required with their occurrence. (II)

9.

Describe the role of the FDA related to control of pharmaceuticals including new drug development and approval for use and regulations that control the use of investigational new drug (INDs) and new drug application (NDAs) by a nuclear medicine facility. (III)

10.

Discuss how reimbursement effects the use of various pharmaceuticals and the resulting impact on patient care. (IV)

11.

Discuss how safety considerations and efficiency should determine hotlab layout. (V)

12.

Discuss dose levels for a typical nuclear medicine procedures and the factors that affect a patient's radiation dose. (VI)

13.

Discuss the hazards to a fetus/embryo or breastfed baby when the mother is administered a radiopharmaceutical including procedures and precautions employed to decrease hazard potential. (VI)

14.

Describe the potential adverse reactions that can occur during and after administration of a radiopharmaceutical including signs and symptoms, causes, actions to be taken and reporting mechanisms. (VII)

15.

Discuss general principles of radiochemistry to include oxidation states, reduction techniques, physical and chemical properties of Tc-99M, tagging processes used to label pharmaceuticals and the various methods for tagging blood components with radionuclides. (VIII)

16.

Discuss the principles and operation of radionuclide generators, factors that affect generator yield and the differences and advantages/disadvantages of wet and dry generators. (IX)

17.

Describe the configuration and components of a Mo99/Tc99m generator and a Rb81/Kr81m generator. (IX)

18.

Calculate yield, current activity and efficiency of a Mo99/Tc99m generator. (IX)

19.

Describe the methods for determining radionuclidic and radiochemical purity and required calculations including impurity limits and sources for error. (X)

20.

Describe the test method for determining sterility and apyrogenicity and the advantages and disadvantages of the methods for detecting pyrogens. (X)

21.

Describe the procedure for preparing a Tc-99m labeled kit including kit components and their purpose, reconstitution of a lyophilized Tc-99, techniques for compounding radiopharmaceutical kits and the documentation requirements when radiopharmaceutical kits are prepared. (XI)

22.

Adhering to NRC allowable dose ranges and calibration requirements, calculate adult and pediatric dose ranges. (XII)

23.

Discuss biologic localization of radiopharmaceuticals in humans including plasma clearance, uptake, redistribution and excretion. (XIII)

24.

Discuss the following for each radiopharmaceutical used in nuclear medicine: alternate names; applicable studies; dose ranges and routes of administration; chemical and physical properties; method of preparation; biorouting mechanisms, critical organ doses, gonadal dose, whole body dose; quality control considerations and limits; precautions and adverse reactions; and interfering agents an their effects. (XIV)

25.

Describe sources, measurement and properties of radiation including physical and chemical characteristics, half-life and kinetic energy in relation to radioactive particle and photons. (XIV, XV, XVI, XVII)

26.

Explain cell biology including function, molecular components, deoxyribonucleic acid (DNA) synthesis, mitosis and meiosis and the cell replication cycle. (XVIII)

27.

Describe the various interactions of radiation with matter including direct and indirect action of ionizing radiation on the cell, linear energy transfer (LET) and relative biological effectiveness (RBE), free radical formation and the target theory. (XIX)

28.

Discuss radiation genetics including mutations, carcinogensis and the process used by cells to repair genetic damage. (XX)

29.

Discuss possible cellular responses to radiation including restitution, division delay, cell synchrony, interphase death, reproductive failure and chromosome stickiness. (XXI)

30.

Discuss various physical and biological factors that can affect the response of cells to radiation. (XXII)

31.

Discuss radiosensitivity and cell populations including the Law of Bergonie and Tribondeau and the five categories of cells based on radiosensitivity as established by Rubin and Casarett. (XXIII)

32.

Discuss tissue and systemic responses to radiation including effects of irradiation, tissue repair and radiation syndrome of the hematopoietic, gastrointestinal, cardiac and central nervous systems. (XXIV)

33.

Describe the potential effects of radiation on the embryo/fetus related to stage of development. (XXV)

34.

Using proposed models that relate radiation dose to effects, describe late effects of radiation exposure including non- specific life shortening, cancer induction, cataract instigation and other diseases. (XXVI)

35.

Discuss concepts related to radiation doses including factors that influence absorbed dose, critical and target organs, gonadal exposure and the classical and medical internal radiation dose (MIRD) methods for calculating absorbed doses. (XXVII)

36.

Discuss the risk-to-benefit ratio of radiation exposure in terms of diagnostic and therapeutic nuclear medicine procedures. (XXVIII)

MCCCD Official Course Outline:

DMI276  2003 Fall – 2009 Summer II

Nuclear Medicine Theory III

I. Introduction

A. Definitions

1. Nuclide versus isotope

2. Radionuclide and radioactivity

3. Radioactive drug (legal definition)

4. Units of radioactivity

5. Specific activity

6. Specific concentration

7. Carrier content

8. Half-life

B. Basic characteristics of radiopharmaceutical

1. Radioactive component

2. Pharmaceutical component

C. Desirable characteristics for a nuclear medicine (NM) radionuclide

1. Limiting agents

a. Patient's radiation dose

b. As low as reasonably achievable (ALARA)

c. Sufficient photon flux and activity for imaging

d. Speed of uptake and imaging times

e. Instrument limitations

f. Diagnostic versus therapeutic requirements

2. Ideal characteristics for diagnostic nuclide

a. Type of radiation

b. Energy

c. Monoenergetic versus multiple energies

d. Half-life

3. Ideal characteristics for therapeutic nuclide

a. Type of radiation

b. Energy

c. Half-life

D. Desirable characteristics for a NM pharmaceutical

1. Non-invasive, non-pharmacologic

2. Clearance time

a. Plasma clearance

b. Target uptake

c. Target clearance

d. Biological half-life

3. Target-to-background

4. Ease of preparation

5. Shelf-life

E. Routes of administration

1. Oral

2. Intravenous injection

3. Inhalation

4. Intrathecal injection

5. Intracavitary injection

6. Subcutaneous injection

7. Urethral infusion

II. Radiation protection and Regulations in Reference to Radiopharmaceuticals

A. Licnesing and regulatory control of radiopharmaceuticals

1. Nuclear Regulatory Commission (NRC) and agreement states

2. Food and Drug Administration (FDA)

3. Department of Transportation (DOT)

4. Occupational Safety and Health Administration (OSHA)

5. Environmental Protection Agency (EPA)

6. United States Pharmacopeia (USP)

B. Review safe handling of radioactive materials

1. Sources of exposure in NM

2. Principles of reducing exposure

a. As low as reasonably achievable (ALARA)

b. Time

c. Distance

d. Shielding

3. Reducing exposure from various sources

a. Ingestion

b. Inhalation

c. Absorption

d. Storage and control of licensed material

e. Quality management program for therapeutic radiopharmaceuticals

1. Patient identification

2. Dose ranges

3. Written directives

4. Informed consent

C. Recordable and reportable events

1. Definitions

2. Procedures following occurrence

D. Dose calibrator possession and quality control requirements

1. Dose measurement requirements

2. Allowable dose ranges

3. Dose calibrator quality control

E. Dose measurement requirements

F. Permissible Mo-99 concentration

G. Use and labeling of syringe shields and vial shields

H. Storage and dispensing of radioactive volatiles. Gases and aerosols

1. Storage requirements

2. Room concentration limits

3. Negative pressure requirements

4. Calculation of room clearance time

5. Postings

6. Handling I-131 liquid

I. Radioactive packages

1. Receipts

2. Shipment

3. Labeling

J. Waste disposal procedures and regulation

1. Waste exempt from disposal regulations

2. Decay-in-storage

3. Discharge into sewer system

4. Discharge into atmosphere

5. Transfer to authorized recipient

K. Control of contamination

1. Ambient dose rate survey

a. Survey instrument requirements

b. Survey instrument quality control

c. Procedures

d. Action and trigger levels

2. Removable contamination survey

a. Procedures

b. Action and trigger levels

3. Decontamination of minor and major spills

a. Definitions

b. Procedures

III. FDA Control of Pharmaceuticals

A. Scope of control

B. Research requirements

1. Basic research

2. Investigational new drug (IND)

3. New drug application (NDA) and approval

C. Regulations for use of IND or NDA in nuclear medicine facility

IV. Effects of Reimbursement on the Use of Radiopharmaceuticals

A. Importance of reimbursement

B. Who controls reimbursement

C. How it affects use of radiopharmaceuticals

V. Radiopharmacy Design

A. Layout

B. Safety considerations

C. Record keeping computers

VI. Radiation Exposure to Nuclear Medicine Patients

A. Factors affecting dose to individual

1. Dose administered

2. Types of radioactive emissions

3. Physical half-life

4. Chemical and physical states

5. Pathological conditions

6. Age of patient

B. General dose levels in NM

1. General exposure ranges

2. Risks

C. Hazards and precautions for pregnant women

1. Sources to irradiation to fetus

2. Radiosensitivity of fetus

3. Estimated dose to fetus from nuclear medicine procedures

4. Actions after exposure

D. Hazards and precautions for nursing mothers

1. Secretion of radionuclides in breast milk

2. Hazard to nursing infant

3. Estimated dose to fetus from NM procedures

4. Precautions

VII. Adverse Reactions

A. General information

1. Frequency

2. Radiation versus pharmaceutical reaction

3. Terminology

B. Vasovagal reaction

1. Signs and symptoms

2. Actions

C. Pyrogenic

1. Signs and symptoms

2. Actions

D. Allergic

1. Signs and symptoms

2. Actions

E. Anaphylactic

1. Signs and symptoms

2. Actions

F. Reporting mechanism

1. Investigational new drug (IND)

2. All other drugs and radiopharmaceuticals

3. In-house

VIII. Radiochemistry

A. Definitions

1. Types of aqueous solutions

2. Chemical species

B. Reactivity

1. Valence state

2. Free radicals

3. Oxidation numbers

4. Oxidation/reduction reactions

C. Chemical bonds

D. Technetium chemistry

1. Terminology and chemical formulas

2. Oxidation states

a. Desirable states

b. Reducing agents

c. Reoxidation

3. Types of technetium compounds

4. Radiolabeling with Tc-99m

a. Hydrophilic bonds

b. Lipophilic bonds

5. Undesirable technetium complexes

a. Free pertechnetate

b. Hydrolyzed-reduced technetium

c. Undesirable lipophilic states

6. Radiolabeling with long-lived radionuclides

7. Tagging blood components

a. Anticoagulants

b. Blood withdrawal/reinjection techniques

c. Red blood cells

d. White blood cells

IX. Radionuclide Generators

A. Principles

1. Parent/daughter relationship

2. Equilibrium

3. Transient versus secular equilibrium

4. Effects of elution

B. Mo99/Tc99m generators

1. Components and configuration

2. Changes in activity with time and elution

3. Elution efficiency

4. Calculating yield

5. Elution technique

6. Wet versus dry

7. Causes of fluctuation in yield

a. Molybdenum loading inconsistencies

b. Channeling

c. Mechanical problems

C. Rb81/Kr81m generators

1. Configuration

2. Changes in activity with time and elution

3. Useful lifespan

X. Quality Control

A. Radionuclidic purity

1. Definition

2. Basic calculation

3. Effects of impurities

4. Sources

5. Test methods

a. Shield method

b. Mock molybdenum method

c. Spectrometry

6. Limits

a. Mo99 in Tc99m

b. Other nuclides

7. Purity versus time

B. Radiochemical purity

1. Definition

2. Basic calculation

3. Effects of impurities

4. Sources

5. Test methods

a. Thin layer chromatography

b. Ion exchange column

6. Limits

7. Purity versus time

C. Chemical purity

1. Definition

2. Alumina in Tc99m generator elutate

a. Source

b. Effects of impurities

c. Test method

d. Calculation

e. Limits

3. Impurities in other radiopharmaceuticals

D. pH

1. Definition

2. Effects of impurities

3. Desired range

4. Test methods

E. Particle size

1. Definitions and ranges

2. Test methods

3. Limits

a. Macroaggregated albumin (MAA)

b. Liver imaging colloids

c. Lymphoscintigraphy colloids

F. Visual appearance

1. Color

2. Clarity

G. Sterility

1. Definition

2. Effects of contaminants

3. Sources of contaminants

4. Sterilization methods

5. Test methods

6. Maintaining sterility

H. Pyrogenicity

1. Definition

2. Effects of contaminants

3. Sources of contaminants

4. Methods for achieving apyrogenicity

5. Test methods

a. Rabbit test

b. Limulus Amebocyte Lysate (LAL) test

c. Comparison

XI. Preparing Tc99m-Labeled Kits

A. Kit components

1. Complexing agent

2. Reducing agent

3. Stabilizer

4. pH buffer

5. Atmosphere

B. Kit production

1. Sterilization

2. Lyophilization

C. Reconstitution process

1. Diluent

2. Factors to be considered

a. Volume limits

b. Activity limits

c. Post-reconstitution shelf-life

d. Storage requirements

D. Record Keeping

E. Compounding Technique

XII. Dose Determination

A. Dose range

1. Factors affecting dose determination

a. Organ or system size

b. Photon flux

c. Radiation dose

2. NRC acceptable ranges

3. NRC calibration requirements

B. Calculation of dose to be administered

1. Specific concentration

2. Volume to be administered

3. Dilution of doses

4. Adjusting unit doses

5. Accounting for decay

a. Decay calculation

b. Decay factor tables

c. Universal decay table

C. Calculation of pediatric doses to be administered

1. Factors affecting pediatric dose determination

a. Organ-to-body ratio

b. Radiosensitivity

c. Metabolic activity

2. Methods for administered dose calculation

a. Minimum and maximums

b. Body surface area

c. Administered dose per unit weight

d. Clark's Rule

e. Other methods

f. Comparison of methods

XIII. Biorouting

A. Clearance and uptake times

1. Plasma clearance

2. Organ/tissue uptake and retention

3. Organ clearance and redistribution

4. Exretion routes

5. Biological half-life

B. Mechanisms

1. First transit

2. Simple exchange definition

3. Active transport

4. Capillary blockage

5. Compartment localization

6. Electrostatic binding

7. Bulk flow

8. Phagocytosis

9. Antibody and antibody fragment localization

10. Receptor localization

11. Cellular sequestration

XIV. Individual Radiopharmaceuticals and Interventional pharmaceuticals

A. Alternate names

B. Studies for which radiopharmaceutical is used

C. Dose range and route of administrative for each study

D. Specific chemical and physical properties

E. Method of preparation

F. Biorouting mechanisms, including initial uptake, redistribution and exretion

G. Critical organ doses, gonadal dose, whole body dose

XV. Review of characteristics of Radiation

A. Types of radiation

1. Gamma rays

2. X-rays

3. Betas particle

4. Positrons

5. Alpha particles

B. Half-life

C. Energy

XVI. Sources of Radiation

A. Environmental

1. Natural

2. Manmade

B. Medical

C. Occupational

XVII. Measurement of Radiation and its Effects

A. Exposure

B. Absorbed dose

C. Dose equivalent

XVIII. Review of Cell Biology

A. Cell structure

B. Molecule components

1. Water

2. DNA

3. Others

C. Cell reproduction

1. DNA synthesis

2. Mitosis

3. Meiosis

D. Cell replication cycle

XIX. Interaction of Radiation with Matter

A. Direct action

B. Indirect action

C. Linear energy transfer

D. Relative biological effectiveness (RBE)

E. Free radicals

F. Target theory

XX. Radiation Genetics

A. Causes and effects of generic mutations

1. Spontaneous mutation

2. Mutagenesis

3. Carcinogenesis

4. Gene mutations and cancer

B. Effects of radiation on DNA

C. Chromosome and chromatid aberrations

D. Repair versus mutation

XXI. Cellular Responses to Radiation

A. Stage of cell replication cycle versus radiosensitivity

1. Repair mechanism

2. Apoptosis and gene p53

B. Consequences of irradiation

1. Restitution

2. Division delays and cell synchrony

3. Interphase death

4. Reproductive failure

5. Chromosome stickiness

C. Survival curves

XXII. Factors Affecting Cellular Response to Radiation

A. Relative beiological effectiveness (RBE)

B. Physical Factors

C. Chemical Factors

D. Biological Factors

XXIII. Radiosensitivity and Cell Populations

A. Law of Bergonie and Tibondeau

B. Cell compartment categories

1. Stem

2. Transitional

3. Differentiated

C. Cell populations (Rubin & Casarett)

XXIV. Tissue and Systemic Responses to Radiation

A. Acute verses late effects

B. Healing of irradiated tissue

C. Total-body irradiation

1. Sources of information

2. Hematopoietic syndrome

3. Gastrointestinal syndrome

4. Central nervous system syndrome

5. Cardiac shock syndrome

XXV. Effects of in Utero Irradiation

A. Radiosensitivity of embryo/fetus

B. Phases of embryonic/fetal development (Russell and Russell)

C. Effects of radiation versus phase of development

XXVI. Late Effects of Radiation Exposure

A. Relating radiation exposure to specific effects

1. Dose versus effect models

2. Problems associated with researching radiation-induced effects/disease

B. Non-specific life-shortening

C. Genetic effects (spontaneous mutation versus radiation induced damage

D. Carcinogenesis

E. Cataract instigation

F. Other diseases

XXVII. Radiation doses

A. Factors influencing absorbed dose form internal sources

1. Concentration and organ mass

2. Effective half-life

3. Physical and chemical characteristics of radionuclide

4. Absorbed fraction

5. Cross-irratiation

B. Critical and target organs

1. Target organs

2. Non-target organs

3. Gonadal exposure

C. Absorbed dose calculations

1. Classical and MIRD methods

2. Formulas

3. Charts and tables

XXVIII. Risk-to-Benefit Ratios

A. Radiation hazard versus medical need

B. Diagnostic exposures

1. Exposure form various sources (x-ray, computed tomography, etc.)

2. Radiation levels in nuclear medicine

C. Therapeutic exposures

1. Exposure from various sources (radiation therapy, implants, etc.)

2. Radiation level in nuclear medicine

D. Quality control consideration and limits

E. Precautions and adverse reactions, including special handling requirements

F. Interfering agents and their effects