Advances in Internal Dosimetry - HPS Chaptershpschapters.org/northcarolina/spring2009/TPM.5.pdf ·...
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Advances in Internal Dosimetry
North Carolina Chapter
Health Physics Meeting
March 12, 2009
Michael StabinDept of Radiology/Radiological Sciences
Vanderbilt UniversityNashville, TN, USA
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Radiation Dosimetry in Nuclear Medicine
• Diagnostic agents
• Therapy agents
• “Off the shelf”, standardized
• Patient-individualized
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Radiation Dosimetry in Nuclear Medicine
• Input data– Extrapolated animal data
• Harvested organs
• Micro-PET/SPECT
– Human image data• Standardized, average/median kinetics and body models• Individualized adjustments (e.g. organ mass scaling)• Patient-specific CT-based body model
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Planar Gamma Camera Data
• Attenuation correction
• Calibration factor
• Scatter correction
C
f
eII
A j
tPA
ROIeµ−=
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Tabulated Dose Conversion Factors
• Precalculated
• Lookup tables – MIRD, ICRP literature, RADAR site
• Software programs (e.g. MIRDOSE, OLINDA/EXM)
• Kinetic data + DCFs → Standardized dose estimates
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The RADAR Web Sitehttp://www.doseinfo-radar.com
• On-line resource for standardized internal dose data
• Decay data, dose conversion factors, software, training courses, guidance documents
• Internal/external dose calculations
• Radiation workers, nuclear medicine pts
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Overview of the RADAR SystemInternal Sources:
Kinetic Models -Radiopharmaceuticals
Kinetic Models -Occupational Radionuclides
Radionuclide Decay Data
Specific AbsorbedFractions - Phantoms
Dose ConversionFactors
External Source Configuration
Radiation Dose Estimates and Distributions
Linking of RadiationDoses to Biological Effects
External Sources:
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RADAR is all about…
….helping people get good dose information when they need it, i.e right now!
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Goal: standardized, but…….
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RADAR Dose Factors• We have calculated dose factors for our >800
radionuclides for:
• Get the data by electronic download at our US site or at our European mirror site (Milan).
Adult Male Adult Female
15-year-old 3 month pregnant female
10-year-old 6 month pregnant female
5-year-old 9 month pregnant female
1-year-old MIRD Head and Brain Model
Newborn Prostate Gland Model
Unit Density Sphere Model Peritoneal Cavity Model
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R
1959 1975 2008
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Adult equation- based model (MIRD/ICRP - 1975)
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Equation-based models of children and adults (Cristy/Eckerman, 1987)
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Anterior views of the NURBS models of the adult male (left) and adult female (right)
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Adult Male
Adult Female
10-yr-old Male
10-yr-old Female
5-yr-old Male
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So we’ve improved on the standardized models….but…..
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Biodistribution and Dosimetry of 99mTc-RP527…J Nucl Med Vol. 42 No. 11 1722-1727
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Cumulative excretion of Ho-166 DOTMP in twelve subjects (6 ♀, 6 ♂) with multiple myelomaBreitz et al. J Nucl Med 2006; 47:534–542
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Organ Mass Scaling
• For electrons, the scaling is:
• For photons, the scaling is:
2
112 m
mDFDF =
3/2
2
112
3/1
1
212
Φ=Φ
=
m
m
m
mφφ
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Liver >> Liver
1.00E-05
1.00E-04
1.00E-03
1.00E-02
0.01 0.1 1 10
Energy (MeV)
SA
F (
1/g
)
45 kg Female
55 kg Female
66 kg Female
74 kg Female
Liver >> Lungs
1.00E-06
1.00E-05
1.00E-04
0.01 0.1 1 10
Energy (MeV)
SA
F (
1/g
)
45 kg Female
55 kg Female
66 kg Female
74 kg Female
Spleen >> Liver
1.00E-08
1.00E-07
1.00E-06
1.00E-05
1.00E-04
0.01 0.1 1 10
Energy (MeV)
SA
F (
1/g
)
45 kg Female
55 kg Female
66 kg Female
74 kg Female
Spleen >> Lungs
1.00E-06
1.00E-05
1.00E-04
0.01 0.1 1 10
Energy (MeV)
SA
F (
1/g
)
45 kg Female
55 kg Female
66 kg Female
74 kg Female
Selected photon SAFs, Adult Models of different stature
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Uncertainties in Internal Dose Calculations for Radiopharmaceuticals
J Nucl Med 2008; 49:853–860
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Patient-individualized Modeling
• Mass-based adjustments to standardized organ doses take a step in this direction.
• Creating patient-individualized models for therapy is a quest for realism and relevance in dose calculations.
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Applications
• Existing codes:– 3D-ID, 3D-RD (MSKCC/JHMI)– RMDP (Royal Marsden Hospital, UK)– SIMIND (Univ of Lund)– Vanderbilt – voxel images + GEANT4
radiation transport– RTDS (COHMS)– “Mr. Voxel” (St. George Hospital, Sydney,
Australia)
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FIGURE 3. (A) Summed coronal 124I PET image slices obtained on day of 124I administration (day 0) and on subsequent 2 days are depicted using same intensity level. Cross-hairs show plane of intersection for corresponding transverse slices through tumor 2, shown immediately below coronal images. (B) Image of absorbed dose distribution in tumor 2, magnified to highlight spatial distribution of absorbed dose within this tumor. Color-coded isodose contours are superimposed as follows: yellow = 75%, red = 50%, blue = 25%, and green = 10% of maximum absorbed dose to tumor (400 Gy). Three different foci of enhanced absorbed dose are observed and designated 1–3 as shown. Kolbert et al. J Nucl Med Vol. 45 No. 8 1366-1372.
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One slice of RIT patient CT image, SPECT image, and corresponding dose-rate map. Yuni et al. J Nucl Med Vol. 46 No. 5 840-849.
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Strigari et al.: Tumor control probability in systemic radiotherapyMedical Physics, Vol. 33, No. 6, June 2006
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+
0
XTB BED RN BED
0
Combined BED
0Bodey, Flux and Evans (Royal Marsden Hospital, UK)
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The Case for Patient-Specific Dosimetry
in Nuclear Medicine Therapy
CBR, Volume 23 (3): 273-284, 2008
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Wiseman et al. JNM 44(3):465-474
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Shen et al. JNM 43 No. 9 1245-1253
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Siegel et al. JNM 44(1): 67-76
Measurement of pt-specific levels of biomarker FLT3-L
R = 0.86 1/PN vs. Adj. dose
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Correlation tumor response vs dose (Gy)90Y Octreother, End of treatment and after 1 year
n = 22
R2 = 0.6104
R2 = 0.8286
-80
-60
-40
-20
0
20
40
60
80
100
0 100 200 300 400 500 600
Gy
% t
um
or
red
uc
tio
n
after 1 year
end treatment
Dr. S. Pauwels, 15th IRIST Meeting, Rotterdam, May-2002, J Nucl Med. 2005 Jan; 46 Suppl 1:92S-8S.
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• Kobe et al. – treatment of benign and malignant thyroid disease (Nuklearmedizin 2008).
• Multi-year follow-up of over 2500 patients, individually tailored patient thyroid dosimetry to a targeted total dose, with ultrasound measurement of subject thyroid mass and adjustment of the procedure to account for differences between observed effective retention half-times between studies involving the tracer activity and the therapy administration.
• Obtained a 95% first treatment efficacy was found.
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Success rates of Graves’ disease therapy at 12 months post therapy characterized by Kobe et al. using therapy guided by
patient-specific dose calculations (black bars), with comparison to those of others (grey bars).
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Conclusions
• Diagnostic applications – “off the shelf” is fine.
• Therapy – fixed activity or fixed activity/g or m2 with no dosimetry cannot yield any meaningful information about dose/response or dose/toxicity.
• Proceeding with therapy with no knowledge of radiation dosimetry not in the best interests of patients (current or future).
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Conclusions
• Radiation dosimetry, of a quality and level of patient specificity equivalent to that in external beam therapy, is essential to progress in nuclear medicine therapy.
• Important issue in post-marketing risk evaluations and delivery of higher quality care to patients.
• Mandated by the Euratom 1997 Council Directive, and spreading in practice across Europe.
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Conclusions
• Keys to success:– Standardization– Clinical acceptance – Implementation of 3D techniques– Importance of biological factors
• BED• Patient-specific kinetics, anatomy, response factors
• The question is not whether, but how we will do patient-specific dosimetry in therapy.