1. Radiophamaceuticals in Nuclear Cardiac Imaging Vasken Dilsizian, M.D. Professor of Medicine and Radiology Director of Cardiovascular Nuclear Medicine and Cardiac Positron Emission Tomography University of Maryland School of Medicine

2. Radiopharmaceuticals Used in Nuclear Cardiac Imaging Procedures Myocardial perfusion SPECTPET Thallium-201Rubidium-82 Tc-99m SestamibiN-13 ammonia Tc-99m Tetrofosmin Cardiac function - Tc-99m Pertechnetate Myocardial metabolism - F-18 Deoxyglucose

3. Clinical Application of Nuclear Cardiac Imaging Procedures in the Pediatric Population Congenital Heart Disease Diagnosis of Coronary Circulation Anomalies Kawasaki Disease Hypertrophic Cardiomyopathy Monitoring Chemotherapy

5. (Components of the Cardiac Sarcomere)

12. Administration of Radiopharmaceuticals in the Pediatric Population It is common for the radiopharmaceutical doses to be based on: Body Weight Body Surface Area Another approach is to administer “Relative Dose” based on radiation exposure. That is, mCi administered to a child that gives the same absorbed radiation as 1 mCi administered to an adult Reynolds JC, Proceedings of Workshop for Treatment of Thyroid Cancer in Childhood, NIH 1992

13. Goals of Nuclear Imaging in the Pediatric Population Inject the lowest dose possible without sacrificing “Image Quality” or “Diagnostic Accuracy” Risk vs Benefits: Risk of radiation exposure vs benefits of understanding the underlying disease process (inherent in all medical decisions)

14. Radiation Exposure With Studies Involving Radiopharmaceuticals Radiopharmaceuticals produce nonhomogeneous exposure to the whole body. That is, exposure dose varies for each organ depending on the biokinetics of the radiopharmaceutical.

15. Various Concepts Used to Evaluate the Total Risk of a Procedure Total-body or Whole-body dose: The total energy deposited in the body divided by the mass of the body. This approach assumes a uniform whole- body exposure to radiation. Effective dose (E) or Effective dose equivalent (H E ): Involves multiplying individual organ doses by risk weighing factors and summing the individual contributions into a single dose.

16. Tissue Weighing factor (w T ) The values of w T take into account the numbers of 1) fatal cancers and 2) risk of hereditary disease above normal incidence per unit of ionizing radiation for each organ system for which such effects are known to occur.

17. CALCULATION OF EFFECTIVE DOSE The effective dose is the sum of the weighted equivalent doses in all the tissues and organs of the body. It is given by the expression: E =  T (w T x H T ) where: E = the effective whole body dose w T = the tissue weighting factor for tissue T H T = the equivalent dose in tissue or organ T; absorbed dose averaged over a tissue or organ and weighted for the radiation quality. The radiation quality factor for clinical radiation (photons, x-rays) is 1; thus, the equivalent dose is equal to the absorbed organ dose. NIH RSC Report: Improving Informed Consent for Research Radiation Studies, 10/17/2001

18. Tissue Weighting Factors, w T (ICRP 73, 1996) 1 Remainder of tissues or organs = 0.05 1 The values have been developed from a reference population of equal numbers of both sexes and a wide range of ages. In the definition of effective dose, they apply to workers, to the whole population, and to either sex. Gonads0.20 Bone Marrow0.12 Colon0.12 Lung0.12 Stomach0.12 Bladder0.05 Breast0.05 Liver0.05 Esophagus0.05 Thyroid0.05 Skin0.01 Bone Surface0.01 wTwT wTwT Organ International Commission on Radiological Protection (ICRP), publication 73, 1996 NIH RSC Report: Improving Informed Consent for Research Radiation Studies, 10/17/2001

19. Calculation of Effective Dose for 10mCi of FDG in an Adult Subject Breasts 0.3400.0500.017 Esophagus 0.4400.0500.022 Stomach 0.470 0.1200.056 Colon 0.4820.1200.058 Heart 2.2000.0250.055 Liver 0.5800.0500.029 Lungs 0.6400.1200.077 OrganDose (rem)WTWT Effective Dose Effective Dose NIH RSC Report: Improving Informed Consent for Research Radiation Studies, 10/17/2001 Dosimetry Source: Coronado, L. (F-18)FDG Internal Rad Dosim for Research Protocols, NIH, 10/30/91 Ovaries 0.5300.2000.106 R. Marrow 0.4700.1200.056 Bone 0.4100.0100.004 Skin 0.3000.0100.003 Thyroid 0.3900.0500.020 Bladder 3.2000.0500.160 Remainder 0.6890.0250.017 Effective Dose WTWT Dose (rem)Organ 1.000 0.680

20. Radiation Risk Estimation The additional fatal cancer risk for a subject group, participating in a clinical or research radiation study, can be estimated by the following expression: (Total effective dose for the study, in rem) X (fatal cancer risk per rem for age group) NIH RSC Report: Improving Informed Consent for Research Radiation Studies, 10/17/2001

21. Nominal Probability Coefficients for Stochastic Effects Detriment x 10 –4 per rem Exposed Population Fatal Cancer Non-fatal Cancer Severe Hereditary Effects Total Children (0-19) 8.0 1.6 11.20 Adult workers (20-60) 4.00.8 5.60 Geriatric (over 50) 1.00.20.65 1.46 Whole Population (0-90) 5.01.01.3 7.30 International Commission on Radiological Protection (ICRP), publication 60 (p.22) For children, the risks are 2-3 times greater than for adults, while for individuals over 50 years of age, the risks are 1/5 th to 1/10 th of that of younger cohorts.

22. Radiation Risk Estimation (Total effective dose for the study, in rem) X (fatal cancer risk per rem for age group) As illustrated in the previous effective dose calculation (FDG scan of 10 mCi), the additional estimated increase in fatal cancer risk for the adult subject is as follows: (0.680 rem) (4.0 x 10 -4 per rem) = 0.00027 = 0.027 % Note that the natural incidence of fatal cancer is 25%. Therefore, the theoretical total risk of fatal cancer for the group of adult subjects participating in this example study is predicted as 25.027 %, or, rounded to 25.03%. It is important to remember that effective dose is a theoretical quantity; no organ or system, including the total body, actually receives the calculated dose. NIH RSC Report: Improving Informed Consent for Research Radiation Studies, 10/17/2001

23. Radiation Dose Guideline Established for “Research” Subjects at the NIH Previous Guideline: Organ dose of 3 rem - quarterly Organ dose of 5 rem - annual Current Guideline: Total effective dose of 5 rem – annual Guideline Value for Pediatric Subjects (<18 yrs) 1/10 th the adult value, or 0.5 rem per year NIH RSC Report: Improving Informed Consent for Research Radiation Studies, 10/17/2001