Advances in Internal Dosimetry

North Carolina Chapter

Health Physics Meeting

March 12, 2009

Michael StabinDept of Radiology/Radiological Sciences

Vanderbilt UniversityNashville, TN, USA

Radiation Dosimetry in Nuclear Medicine

• Diagnostic agents

• Therapy agents

• “Off the shelf”, standardized

• Patient-individualized

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

Planar Gamma Camera Data

• Attenuation correction

• Calibration factor

• Scatter correction

C

f

eII

A j

tPA

ROIeµ−=

http://jnm.snmjournals.org/cgi/content/full/42/4/579/F4

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

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

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:

RADAR is all about…

….helping people get good dose information when they need it, i.e right now!

Goal: standardized, but…….

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

R

1959 1975 2008

Adult equation- based model (MIRD/ICRP - 1975)

Equation-based models of children and adults (Cristy/Eckerman, 1987)

Anterior views of the NURBS models of the adult male (left) and adult female (right)

Adult Male

Adult Female

10-yr-old Male

10-yr-old Female

5-yr-old Male

So we’ve improved on the standardized models….but…..

Biodistribution and Dosimetry of 99mTc-RP527…J Nucl Med Vol. 42 No. 11 1722-1727

Cumulative excretion of Ho-166 DOTMP in twelve subjects (6 ♀, 6 ♂) with multiple myelomaBreitz et al. J Nucl Med 2006; 47:534–542

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

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

Uncertainties in Internal Dose Calculations for Radiopharmaceuticals

J Nucl Med 2008; 49:853–860

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.

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)

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.

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.

Strigari et al.: Tumor control probability in systemic radiotherapyMedical Physics, Vol. 33, No. 6, June 2006

+

0

XTB BED RN BED

0

Combined BED

0Bodey, Flux and Evans (Royal Marsden Hospital, UK)

The Case for Patient-Specific Dosimetry

in Nuclear Medicine Therapy

CBR, Volume 23 (3): 273-284, 2008

Wiseman et al. JNM 44(3):465-474

Shen et al. JNM 43 No. 9 1245-1253

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

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.

• 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.

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).

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).

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.

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.