Standardization of Radiopharmaceutical Dosimetry

Transcription

1 Standardization of Radiopharmaceutical Dosimetry Jonathon A. Nye, PhD Department of Radiology and Imaging Sciences Emory University SEAAPM 2011 Myrtle Beach, SC

2 Review of Dosimetry Nomenclature Dose Gray (Gy), the total energy absorbed in a medium divided by its mass Equivalent Dose ED (Sv), Dose multiplied by radiation weighting factor ( LET of particle) Effective Dose EDE (Sv), Sum of ED for each organ multiplied by weighting factor based on stochastic effects EDE is used in comparisons of cancer risk Dose of concern when following Federal Limits

3 Radiation Dose Calculations Two general methods to calculate dose Classic Method Follows definition of Gray Accurate for ionizing radiation that has a path length shorter than the absorber More difficult for radiation with larger path lengths Absorbed Fraction Method Developed independently by ICRP and MIRD More versatile and accurate Adopted as the standard method for performing internal radiation dosimetry

4 Direct Method Organ is large compared to the range of the radiation, infinite medium assumption True for α s and most β radiation D(t) α or β =K x E ave x ηx A o m Energy commitment per transition Activity within organ Organ mass If the infinite medium assumption is not satisfied, D(t) γ = v e μr

5 Absorbed Fraction Method Accounts for partial γ ray absorption in a finite medium Developed jointly by, Society of Nuclear Medicine s (SNM) Medical Internal Radiation Dose Committee (MIRD) International Counsel on Radiological Protection (ICRP) Employs Target and Source Organs ϕ = Energy Absorbed by Target Energy Emitted by Source Monte Carlo is used to model the probabilistic interaction laws ϕ is calculated by summing up initial energy in the source organ and comparing to total energy absorbed by the target organ

6 Source and Target A number of configurations are allowed For penetrating radiation, ϕ < 1 For non penetrating radiation ϕ = 1, if S=T ϕ = 0, if S T Absorbed fraction is generally normalized by organ mass,φ, and tabulated Introduction to Health Physics, Chpt. 6, Cember 1996 MIRD Primer for Absorbed Dose Calculations, SNM 1988

7 Anti 1 amino 2 fluorocyclopentyl 1 carboxylic acid (anti 2 [ 18 F]FACPC 1) Male: 333 MBq: 66kg 0 6 min 7 21 min min min min min Nye et al., unpublished data

8 anti 1 amino 3 18 F fluorocyclobutane 1 carboxylic acid (anti 3 18 F FACBC) Male: 388 mci: 111 kg 0 7 min 8 15 min min min min min Nye et al., JNM 2007; 48:

9 Effective Half life The effective half life depends on, the physical half life of the isotope and the biological half life of the labeled molecule or metabolite in the organ λ eff = λ p + λ b The biological half life is organ specific and a function of the excretion properties of the organ. Physical and Biological Decay Biological Decay Only

10 Cumulated Activity and Residence Time Cumulated Activity ~ A o A T = A T (t) x e λeff x t dt (total transitions) Physiological kinetics are contained within the cumulated activity value Data is normalized to the injected dose residence time (τ T ) Activity Activity A T A o τ T τ T = A~ T /A o = 1/λ eff(t) x A T /A o A T (t) Time τ T = ~ A T /A o A T (t) τ T Time

11 Residence Time Residence time is the time integral of the cumulated tps normalized to the injected dose If all the activity is retained in all organs τ T 1/λ P For isotopes. F 18, 1/λ P = 2.64 hrs C 11, 1/λ P = 0.48 hrs Nye et al. 2007, JNM: 48: 1017

12 MIRD Schema Mean Energy Per Transition Δ i = Kη i E i Specific Absorbed Fraction Φ i (r T r S ) = ϕ i (r T r S )/m T Mean Dose per Unit Cumulated Activity S i (r T r S ) = Δ i Φ i (r T r S ) S is tabulated for a variety of phantoms and radiopharmaceuticals (See MIRD Pamphlets) Dose per unit of administered activity is, D/A o = τs Measured from Images Isotope property Phantom model Monte Carlo Model

13 MIRD dosimety software MIRDOSE 3.0 (Stabin et al., JNM 1996; 37: ) S factors for a variety of phantoms Library of radionuclides Exponential fitting routines Dynamic models of GI tract and bladder OLINDA/EXM (Stabin et al., JNM 2005; 46: ) Contains all features of MIRDOSE but 510k (FDA) compliant Expanded radionuclide library Can change organ masses of phantom models Corrections to S values of marrow, bone and skin

14 Dose Limits for Research Volunteers FDA 21 CFR Part 361 has adopted the ICRP 103 recommendations 30mSv for a single injection, 50mSv annually Single organ dose of 50mSv, 150mSv annually Nye et al. 2007, JNM: 48: 1017 Radionuclide Critical Organ Inj. Activity [Mbq] Total WB EDE [msv] # allowed scans FDG urinary bladder wall NH3 urinary bladder wall Rb82 kidneys H2O heart wall FACBC Liver

15 Limitations of MIRD method Values of absorbed fraction are based on models of human anatomy, not individual subjects Assumes activity is distributed uniformly in each organ and, Energy is uniformly deposited throughout the organ Does not work for augur electrons or Y 90 where uptake is non uniform. Residence times are generally based on a small number of subjects Mixed sexes May have different disease states

16 MIRD Anthropomorphic Model Snyder, W. S., Ford, M. R., Warner, G. G., et al. Estimates of absorbed fractions for monoenergetic photon sources uniformly distributed in various organs of a heterogeneous phantom. MIRD Pamphlet No. 5. (Society of Nuclear Medicine) (1969)

17 4D NURBS based Cardiac Torso (XCAT) Paul Segars, PhD

18 More sophisticated models Based on individual subject anatomy S values are created from segmented whole body CT and MR scans of individual subjects Non uniform activity distributions Sub organ level Brain (MIRD Pamphlet No. 15) Heart (MIRD Pamphlet No. 13) Kidney (Bolch et al., 1997, JNM and McAfee et al., 1989, Oak Ridge) Voxel level S values (MIRD Pamphlet No. 17) is of interest in, Radioimmunotherapy (RIT) with radiolabeled monoclonal antibodies Radioiodine therapy of thyroid carcinoma Intratumoral injection of therapy radiopharmaceuticals

19 Courtesy of James Galt, PhD Emory University Nonuniform Radionuclide Uptake FDG PET/CT prior to Y 90 SIR microsphere treatment Y 90 bremsstrahlung SPECT/CT Y 90 SPECT fused with FDG PET

20 Imaging Surrogates for Radionuclide dosimetry

21 Residence Time Variability Six healthy volunteers 3 male (78 ±10 kg, 38 ±16 yrs) 3 female (60 ±19 kg, 34 ±13 yrs 2hr serial WB PET scans Bladder residence times Male: ±0.077 hr Female: ± hr Anti 2 [ 18 F]FACPC Synthetic leucine amino acid analog Male: 290 MBq: 84kg Head motion? Female: 188MBq: 82kg Note MIPs are not normalized to a global maximum Nye et al., unpublished data

22 Internal Radionuclide Dosimetry Resources Medical Internal Radiation Dose (MIRD) Committee of SNM Provides list of current publications and archives Links to software and workshops/meetings Radiation Dose Assessment Resource (RADAR) radar.com/radarhome.html Provides patient dose calculator Links to software and advanced phantom models

23 Summary MIRD scheme is widely accepted for internal radionuclide dosimetry Dose commitment for most nuclear procedures should include CT (Huda et al Converting dose length product to effective dose at CT. Radiology 248; ) Pregnant and child models are now available with OLINDA/EXM Accurately calculating internal dose from therapeutic radiopharmaceuticals remains challenging

24 Thank you!

25 Robert Rohrer, Ph.D. Leader, Organizer, Scientist, Educator Robert Rohrer, Ph.D. ( ) Society of Nuclear Medicine President, Southeastern Chapter Brucer Award, Southeastern Chapter 1993 Executive Director, Southeastern Chapter Preceded Vince Sodd Counselor Emeritus, Southeastern Chapter?-2007 MIRD Committee 1970 s Emory University Professor of Engineering, Radiology, and Physics Emory Williams Teaching Award 1973 Thomas Jefferson Award 1978 Dr. Rohrer was the most inspiring teacher I have ever had, said Debia McCulloch 79C 87G. His wide smile and continued enthusiasm for teaching even introductory physics classes were contagious.