Radioimmunotherapy Dosimetry
William D. Erwin, M.S.
Department of Imaging Physics
UT M. D. Anderson Cancer Center
Radioimmunotherapy
Localized internal radiation therapy of
cancer using radiolabeled antibodies
targeted to specific antigen binding
sites on tumor cells
Radioimmunotherapy:
Radionuclides of Interest
• 90Y (pure β- emitter, more ideal for therapy)
- Bremsstrahlung imaging possible, but non-quantifiable, so
- 111In used as a surrogate for imaging
imageable 172, 247 keV γ’s + similar T1/2 (67 hr vs. 90Y 64 hr)
• 131I (β- + imageable 364 keV γ, but also higher keV γ’s)
• 67Cu (β- + imageable 184 keV γ)
• Miscellaneous other β- emitters (e.g., 186Re, 177Lu)
• Future: emitters for α therapy (211At, 212Bi , 213Bi)?
Radioimmunotherapy:
Routes of Administration
• Intravenous
(most common)
• Intratumoral
• Intra-arterial
•Intraperitoneal
Radioimmunotherapy:
Current Applications
• Non-Hodgkin’s B-Cell Lymphoma
90Y-Zevalin™
(IDEC) FDA approved 2/02 (anti-CD20)
131I-BEXXAR™ (Corixa) FDA approval 6/03 (anti-CD20)
antibodies targeted to other expressed antigens
• Other cancers under investigation
Other Lymphomas, Leukemias
Colorectal, Breast, Liver, Prostate, Renal, misc. GI
Gliomas, Astrocytomas (intra-tumoral infusion)
Radioimmunotherapy Dosimetry:
Regulatory Requirements
• Radiopharmaceutical Clinical Trials
Primarily Safety-Related:
critical organ MTD (rad,cGy), and thus
maximum tolerated administered activity (mCi,MBq)
Efficacy: absorbed dose in tumors (dose-response)
• Approved Therapeutic Agents (package inserts):
Zevalin: www.idecpharm.com/site/science/zevalin_pi.pdf
BEXXAR: www.corixa.com/BEXXAR/bexxarpackageinsert.pdf
organ radiation abs. dose estimates (mean, range)
Radioimmunotherapy Dosimetry:
Organs of Interest
• Whole Body (estimate of average dose over entire body)
• Red Marrow
- radiosensitive
- dose from radioactivity in blood (esp. IV administrations)
• Lungs (radiosensitive)
• Liver, Kidneys (and secondarily, GI tract, Bladder)
- antibody clearance organs
• Spleen
• Thyroid (e.g., free 131I)
Medical Internal Radiation Dosimetry:
Model-Based Approach
• Energy (E) Deposition vs. Radiation Type/Energy
• non-penetrating:
penetrating β+/-’s, e-’s < 4 MeV; γ’s < 10 keV
• Penetrating: γ’s > 10 keV
• Anthropomorphic Computer Phantoms (10)
• Adult M/F; 3/6/9 mo. pregnant; newborn; 1/5/10/15 yo
• Standard (average) organs
- modeled density, volume, shape, location
- 28 Source organs, 27 Target organs
• Dynamic Models: GI and Urinary Tracts
MIRD Source-Target Radiation Dose Model
np = “non-penetrating” radiation
p = “penetrating” radiation
Source s
p (γ’s > 10 keV)
np + p
(t ← s “S” factor = Sp)
(s ← s “S” factor = Snp + Sp)
(t ← s Dose)
(s ← s “self” Dose)
Target t
MIRD Absorbed Dose “S” Factor
• S(t←s) = radiation absorbed dose in t
per unit cumulated activity in s
• Units:
• rad/µCi-hr (traditional)
• mGy/Bq-sec (S. I.)
• radionuclide and source-target specific
MIRD Absorbed Dose “S” Factor
Snp(t←s) = 1/m Σi ∆i×φnp(t←s); Sp(t←s) = 1/m Σj ∆j×φp(t←s)
S(t←s) = Snp(t←s) + Sp(t←s)
m = reference phantom target organ mass
Traditional units: ∆i = 2.13niEi g-rad/µCi-h; Ei MeV
S.I. units: ∆i = niEi kg-Gy/Bq-s; Ei Joule
ni = probability of emission i
φ(t←s) = energy absorbed in t ÷ energy emitted in s
np: = 1 (t = s), 0 (t ≠ s)
= ½ (contents→wall): heart, stomach, GI tract, bladder
p: < 1 (dependent on: radionuclide, phantom, source, target)
Cumulated Activity
Total number of decays in a given region
(µCi-hr, Bq-sec), from a given amount of
internally administered radioactivity, Ainj(0):
Quantitative
Imaging!!!
Ã=
∞
∫ Abio(t)
0
e-λphys t dt,
dt t = time
Residence Time = Ã ÷ Ainj(0) (hr, sec)
∞
= ∫ fbio(t)
0
e-λphys t dt , fbio(t) = Abio(t) ÷ Ainj(0)
f(t) = fraction of injected activity
MIRD Radiation Absorbed Dose
Total Dose: Dt = Σs Ãs × S(t←s)
Units: rad, Gy
FYI: Dose Rate, dDt/dt = Σs Asbio(t) e-λphys t × S(t←s)
Unit Dose: dt = Σs Tress × S(t←s)
Units: rad/mCi, mGy/MBq
Radioimmunotherapy:
Absorbed Dose Estimates
• Previous murine (mouse) or human
biodistribution data
• Pharmacokinetic or compartmental
models
Both poor predictors of variable
biodistribution in individual patients,
so …
Radioimmunotherapy:
Individualized Dose Estimates
• Measurement of absolute uptake vs. time of
radiolabeled compound in the patient
• Input data (Abio(t) e-λphys t) to patient-specific
MIRD dose estimation for:
• organ safety/toxicity limits
• tumor therapeutic efficacy
• treatment planning
Radioimmunotherapy:
Dose Estimate Mass Correction
Stabin MG, SNM 1998
Dt = Dnp + Dp
= Σs Ãs × Snp(t←s) + Σs Ãs × Sp(t←s)
= Ãs/mref Σi ∆i×φnp(t←s) + Ãs/mref Σj ∆j×φp(t←s)
mref = reference phantom organ mass
Correction for Patient Organ Mass:
Dt = Dnp × [mref / mpatient] + Dp × [mref / mpatient]1/3
Pure β- emitter: Dt ≅ Dself = Dnp(t←t) × [mref / mpatient]
Radioimmunotherapy:
Dose Estimate Mass Correction
Organ Mass Estimation
1. Estimate organ volume
V (cc) from CT, MR or SPECT
2. Calculate organ mass
mpatient = V × ρ
ρ ≅ 1.0 g/cc (soft-tissue)
ρ ≅ 0.3 g/cc (lung)
ρ ≅ 1.5 g/cc (bone)
Radioimmunotherapy:
Tracer Principle
Assumption: A small (tracer) diagnostic amount
of radiolabeled compound can be used to
predict the biodistribution of the therapeutic
administration (i.e., does not perturb the
response of the biological system)
ABioTher(t) = ABioDiag(t) x [ AInjTher / AInjDiag ]
Radioimmunotherapy Planning:
Radioactivity Prescription
ATherapy(0) = DTherapy / dDiagnostic
DTherapy = tumor or organ prescribed total
radiation absorbed dose
dDiagnostic = tumor or dose-limiting organ
unit radiation absorbed dose estimate
from diagnostic tracer procedure
Planar Quantitative Imaging
1. [Optional] Transmission Scans (w/o [blank] & w/ patient)
- attenuation correction for geometric mean (GM) quant.
- not required if whole body at t = 0 is employed as
standard for camera sensitivity calibration (see 3 below)
2. Serial, Anterior and Posterior (A/P) images
- immediate (0 hr), then up to 4 – 12 days (out to at least
≥ 2 × T½effMax = [T½bioMax × T½phys] / [T½bioMax + T½phys])
3. Camera Sensitivity Calibration, S: cps/µCi, cps/kBq
- activity standard (reference source) in field-of-view
OR
- whole body region GM cps at t = 0 ÷ Ainj(0)
4. [Optional] Image Scatter Subtraction
Planar Quantitative Imaging
5. Region-of-interest (ROI) counts per sec (cps) vs. time, C(t)
______________________________
GM: √[ CA(t) - BkgdA(t) ] × [ CP(t) - BkgdP(t) ] (A & P)
Effective Point Source (EPS): C(t) - Bkgd(t) (A or P only)
C(t) = total cps in organ/tumor ROI
Bkgd(t) = estimated background cps in organ/tumor ROI
= background ROI cps × (Areaot ÷ Areabkgd)
Areaot = no. of pixels in organ/tumor ROI
Areabkgd = no. of pixels in background ROI
C(t) - Bkgd(t) = net cps in organ/tumor
Planar Quantitative Imaging
6. Conversion to absolute activity: µCi, kBq
- A(t) = (C(t) × ACF) / S; ACF = eµ thickness / 2 (GM), eµ depth (EPS)
- A(t) = (C(t) × Ainj(0)) / Cwb(0) (whole body as std. GM method)
7. Decay Correction: A(t) → Abio(t), fbio(t)
- × eλimaging t, λimaging = imaging isotope decay constant
- mathematical model function fit to biologic component
8. Cumulated activity Ã, residence time Tres
à = ∫ Abio(t)e-λtherapyt dt
Tres = ∫ fbio(t)e-λtherapyt dt
9. Target(s) Radiation Absorbed Dose Estimation
Dt = Σ Ãi × S[t←si]
i
dt = Σ Tresi × S[t←si]
i
Whole Body/Planar
Transmission Scans
Administer
Radiopharmaceutical
Standard
Source
Images
Planar
Emission
Images
Whole Body
Emission
Images
Repeat up to
N days post-injection
Source Organ/Tumor
ROI cps vs. Time
Camera
Sensitivity
(cps/µCi)
Absolute Uptake
TAC (µCi)
Fit TAC/Integrate
for Tres (hours)
Radiation Absorbed Dose
Estimates:
Unit (rad/mCi,mGy/MBq)
or
Total (rad,Gy)
Attenuation
Correction
Factors
Quantitative
Radionuclide
Imaging
Serial
Whole Body
Emission
Imaging:
patient +
reference
(standard)
source of
radioactivity
Quantitative
Radionuclide
Imaging
Serial
Spot View
Imaging:
- separate
images
(patient, std)
- transmission
images
Scatter Correction
- Radionuclide-Dependent (no. of γ‘s, γ energies)
- Object and Imaging System-Dependent
• Object: patient (unique scatter medium)
• System: spatial/energy resolution; crystal thickness; collimation
- Goal: Scatter Free Imaging
• “Pure” photopeak images
• “Pure” attenuation (can use published µ (cm-1) values)
- Energy Window Weighted Image Subtraction
• Dual (DEW) (scatter window below photopeak)
• Triple (TEW) (scatter windows above/below photopeak)
• Quadruple (QEW) (dual photopeak radionuclides, e.g., 111In)
Image Scatter:
Photopeak Contamination
Emission Spectrum for In-111
Emission
EmissionSpectrum
Spectra for
forI-131
I-131
Compton Scatter Window
108108-152 keV
Photopeaks
• Upper Scatter:
• Collimator septal penetration of high energy γ’s
• Compton scatter in crystal
• Lower Scatter: Compton scatter in patient
131I
TEW Scatter Correction
Macey, et al, Med Phys 22:1637, 1995
GM
PP A
PP P
US A
US P
LS A
PP
LS P
GMPP - 0.71GMUS
LS
GMLS - 0.62GMUS
PUS - 0.91LSUS
P
US
PUS
LSUS
Quantitative Imaging: ROIs
Organ
Organ
CtsOiA
CtsOiP
CtsBiA
CtsBiP
Background
Background
Anterior
Posterior
Standard
CtsSiA
Standard
CtsSiP
GM ACF from Transmission Scanning
Ctsp
Ctsp
Lungs
Cts0
Liver
Cts0
ACFGM = eµ Thickness / 2 = [Cts0 / Ctsp]1/2
(Ctsp = Cts0 e-µ Thickness)
GM ACF from Transmission Scanning:
Differing Transmission and Emission
Imaging Radionuclides (e.g., 57Co, 131I)
_________
ACFTrans = eµT Thickness / 2 = √ Cts0 / Ctsp
µT = Transmission radionuclide attenuation coefficient
ACFEmission = e µT (µE ÷ µT) Thickness / 2
___________
ACFEmission = √ (Cts0 / Ctsp)f, f = (µE ÷ µT)
µE = Emission radionuclide attenuation coefficient
Planar ACF from Lateral View
Right Lateral
Left Lateral
Distance
Calibration
Sources
d pixels
t pixels
(GM thickness) (EPS depth, e.g., Post) p pixels, L cm
ACFGM = eµ (t L / p) / 2 (e.g., for A/P Liver)
ACFEPS = eµ (d L / p) (e.g., for posterior Spleen)
(µ, L / p known or measured)
Planar ACF from Tomograms
CT
Liver
Tavg
CT
NM SPECT
Spleen
Tright
Tavg
Tleft
Davg
ACFGM = eµ Tavg / 2
for Ant/Post
Liver, Spleen
ACFEPS = eµ Davg Tavg = (Tright+Tleft) / 2
ACFGM = eµ Tavg / 2
for Posterior
for Ant/Post
Lumbar Spine
Kidneys
Whole Body as Standard GM Method
van Reenen, et al, Eur J Nucl Med 1984
Assumption: Geometric mean (GM) of t = 0 whole
body ROI cps ≡ 100% of injected activity, × [e-µT/2]avg
(average GM attenuation factor over whole body)
Camera sensitivity: SWB = C(0) ÷ Ainj(0)
= k Ainj(0) [e-µT/2]avg ÷ Ainj(0)
= k [e-µT/2]avg
Regional GM activity: AROI(t) = CROI(t) ÷ SWB
= CROI(t) [eµT/2]avg ÷ k
Partial attenuation correction!!!
Radionuclide Conversion
Necessary when imaging and therapy
radionuclides differ (e.g., 111In/90Y labeled
antibody):
Aimaging(t) = Abio(t) e-λimaging t
Abio(t) = Aimaging(t) eλimaging t
Atherapy(t) = Abio(t) e-λtherapy t
Radioimmunotherapy:
Blood-Based Marrow Dosimetry
•
1.
2.
3.
4.
Blood Activity vs. Time @ each of N time points ti:
Draw whole blood (b) sample (X ml) from patient
Measure background cpm in well counter
Measure Cb(ti) – bkgd = cpm/ml for 1 or 2 Y ml subsamples
Measure sensitivity from 1 or 2 Y ml decaying standard(s):
S(ti) = (Cs(ti) – bkgd) / [Astd(0) e-λphysti] (cpm/µCi, cpm/MBq)
5. Calculate biologic activity/ml: Aml(ti)=Cb(ti)eλphysti/[Savg(ti)×Y ml]
Alternatively, at time tend:
1. Measure sensitivity S(tend) (step 4)
2. Measure all Cb(ti) subsamples and simply correct to t = 0 (×
eλphystend), as they are already effectively decay corrected
Radioimmunotherapy:
Blood-Based Marrow Dosimetry
• Calculate whole blood Tresb/ml:
Fit Aml(ti) e-λtherapyti/Ainj(0) to model (e.g., bi-exponential)
e.g., bi-exponential Tresb/ml = 1.443 [f1(0)T1/2eff1 + f2(0)T1/2eff2]
• Calculate Red Marrow Tresrm from model formula:
- Tresb/ml × Massrm × .19 / (1-h) (Sgouros, J Nucl Med 1993)
e.g., MIRD adult Massrm = 1120 g (M), 1050 g (F)
h = hematocrit
- Tresb/ml × Massrm × .25 (DeNardo, et al, Nucl Med Comm 1993)
Doserm←rm = Tresrm × Atherapy(0) × Srm←rm
Radioimmunotherapy:
Image-Based Marrow Dosimetry
DeNardo, et al, Clin Nucl Med 1995
Posterior View
• 5 cm wide L2-L4 region (L)
• Counts/pixel in 1 cm wide background region
• counts/sec-to-total marrow activity:
cps = [L counts – (bkgd × L pixels)] / ∆t
A[t] = cps[t] ÷ S × eµd ÷ .046
S = camera sensitivity calibration
µ = linear attenuation coefficient
d = average L2-L4 depth (e.g., from CT)
.046 = 4.6 % of total marrow in L2-L4
Doserm←rm = Tresrm × Atherapy(0) × Srm←rm
Planar Imaging & MIRD Dosimetry:
Deficiencies
• Overlapping structures in planar images
(e.g., Liver/R Kidney, Tumor/Organ)
• 2-D estimates of 3-D activity, scatter, attenuation
• Average dose over organ/region calculated
(uniform activity distribution is assumed)
• Crude estimate of radiation absorbed dose
(calculated on a MIRD phantom, NOT the patient!)
Future: 3-D Imaging & Dosimetry
Quantitative SPECT-CT
• Removal of overlap of activity (tomographic)
• Quantitative Iterative SPECT reconstruction:
• Resolution recovery
• Attenuation correction: registered CT µ maps
• Scatter compensation
• Absolute µCi, MBq in 3-D (NM’s “holy grail”)
Future: 3-D Imaging & Dosimetry
• SPECT: Cumulated Activity (Sources)
• Registered CT: Radiation Absorption (Targets)
• Patient-Specific 3-D (voxel-level) Dosimetry
• Radiation Transport Code (MCNP, EGS4),
• Dose Point Kernels, or
• Voxel S values
• Answer local dosimetry questions, such as
• organ, tumor dose-volume histograms
• spinal cord adjacent to treated tumor
3-D Imaging & Dosimetry:
CT-based SPECT Attenuation Map
CT (70-80 keV eff.)
SPECT µ map
SPECT-CT
Image Registration
(software or SPECT-CT device)
CT-to-SPECT
µ map
conversion
3-D Imaging & Dosimetry:
Quantitative SPECT
SPECT µ map
SPECT Projections
Iterative
Recon
µCi/cc, µCi
3-D Imaging & Dosimetry:
Dose Calculation
Sources (SPECT)
Targets (CT)
Ã(x,y,z) [uCi-hr,Bq-s]*
radiation absorption media
3-D Dose Calculation:
1. Monte Carlo (MCNP, EGS4)
2. Dose Point Kernels
3. Voxel S Values
3-D Dose Distribution Maps
Define 3-D
Sources/Targets
(volumes of interest)
Dose Volume Histograms
* Ã(x,y,z) computed from either:
1. A combination of a single-point quantitative SPECT volume and source activity vs. time from planar imaging
2. Voxel-by-voxel activity vs. time from spatially registered, serial quantitative SPECT volumes
Quantitative Radionuclide
Imaging & Dosimetry: Examples
• 111In
• 90Y
imaging/90Y dosimetry/therapy
MAb tumor dosimetry
• BEXXAR treatment planning
• Simple methodology based on Zevalin
approved radioimmunotherapy regimen
images
MAb: 111In imaging/90Y dosimetry/therapy
Dual-head, A/P GM whole body imaging
• Blank/transmission scans (57Co sheet source on lower head)
• 111In MAb (5 mCi) emission images (0, 4, 24, 72, 144 hr)
• Photopeak (172/15%, 247/15%) and Scatter (130/34%) images
• Photopeak – (0.4 × Scatter) image subtraction
GM ROI organ quantification method (lungs, liver, kidneys)
• Transmission attenuation correction
• Reference source (50-100 µCi) camera sensitivity calibration
• Model function fit of fbio(t) → Tres (= ∫ fbio(t) × 90Y e-λt dt)
organ unit dose, dDiag (= Trest × St←t × [mref ÷ mpatient(from CT)]
ATher = DTher / dDiag based on prescribed organ dose (e.g., 500 cGy)
90Y
MAb: 111In imaging/90Y dosimetry/therapy
Transmission Imaging
Emission Imaging
111In
A/P × 5
Immed
4 hr
24 hr
72 hr
144 hr
Photopeak Scatter
57Co
Blank
57Co
Patient
111In
Scatter Correction: Energy Windows
based on Gilland, et al, IEEE Trans Nucl Sci 38:761, 1991
Compton Scatter Window
108-152 keV
Photopeaks
MAb: 111In imaging/90Y dosimetry/therapy:
111In Scatter Subtraction
- 0.4 ×
Photopeak
=
Scatter
Corrected
MAb: 111In imaging/90Y dosimetry/therapy:
Kidney ROIs
111In
GM Emission ROIs
Transmission ROIs
Kidney
background
ROI
reference
source
ROIs
Immediate: Ant
57Co
Post
Patient Blank
MAb: 111In imaging/90Y dosimetry/therapy
__________
FIAbio(t) = √CA(t)×CP(t) × eµInThickness/2 × eλInt ÷ SRef
eµInThickness/2:
_________________
√[CROIblank ÷ CROItrans]f
___________
√e f µCoThickness
f = µIn ÷ µCo
= .135 ÷ .161
MAb: 111In imaging/90Y dosimetry/therapy
Kidney volume from CT
N slices
Σ ROIpixelsi×pixel area [cm2]×slice thickness [cm]
i=1
β- MIRD organ
(self-)dose scaling:
90Y
× MIRD ref. mass
pat. mass
Mass = V (cc) × ρ (g/cc)
ρ = .9869 (soft-tissue)*
ρ = .2958 (lung)*
* from MIRD Pamphlet No. 5, Revised 1978
90Y
MAb Tumor Dosimetry
Dual-head, A/P GM whole body imaging
• Blank/transmission scans (57Co sheet source on lower head)
•111In MAb (5 mCi) emission images (4,24,72,144 hr)
• Photopeak (172/15%, 247/15%) and Scatter (130/34%) images
• Photopeak – (0.4 × Scatter) image subtraction
GM ROI tumor quantification method
• Transmission attenuation correction
• Reference source (50-100 µCi) camera sensitivity calibration
• Biologic fraction of inj. activity vs. time (111In decay corr.)
• Model function fit of fbio(t) → Tres (= ∫ fbio(t) × 90Y e-λt dt)
Active tumor mass estimation (CT volume × 1 g/cc)
MIRDOSE v 3.1 Nodule Module S value for tumor (rad/µCi-hr)
90Y MIRD β- self-dose (rad) = Tres × S × 1000 × A
ther(mCi)
90Y
MAb Tumor Dosimetry: Tumor ROIs
Emission
(140.5 hr)
Transmission
90Y
MAb Tumor Dosimetry: Tumor TAC
90Y
MAb Tumor Dosimetry: CT Volume
OSIRIS
software
v 3.6.1
Univ. Hosp. of Geneva,
Switzerland
(www.expasy.ch/UIN)
90Y
MAb Tumor Dosimetry: CT Volume
OSIRIS
software
v 3.6.1
99cc = ~99g
(ρ ~ 1 g/cc)
90Y
MAb Tumor Dosimetry: S value
MIRDOSE v 3.1
Nodule Module
Stabin, J Nucl Med
1996; 37:538-546
99 g ~ 100 g (else, must
interpolate between nearest
sphere mass S-values)
D = ~1600 (1593) rad = 16 Gy
(1.79 hr × .0185 rad/µCi-hr × 1000 × 48.1 mCi)
Approved Regimen for BEXXAR:
www.corixa.com/BEXXAR/BEXXARAdminProcess.pdf
Day 0
• Tositumomab (cold antibody) infusion – 450 mg
• 131I-BEXXAR infusion (5 mCi in 35 mg)
• < 1 hr post-inf., pre-void A/P whole body scan (10-30 cm/min)
Day 2, 3 or 4
• post-void A/P whole body scan (10-30 cm/min)
Day 6 or 7
• post-void A/P whole body scan (10-30 cm/min)
Day 7-14
IF normal 131I-BEXXAR biodistribution (whole body Tres, visual)
• Cold antibody infusion (450 mg), then 35 mg 131I-BEXXAR
• 131I mCi based on 65 cGy (low platelets) or 75 cGy to total body
Approved Regimen for BEXXAR:
Whole Body Scanning
Background
Sensitivity
QC Standard
Patient
×3
Approved Regimen for BEXXAR:
Total Body Residence
Time
________________________
CWB(t) = √[CA(t) - CBA(t)] × [CP(t)-CBP(t)]
FIATB(t) = CWB(t) / CWB(0)
TresTB:
1.443 × TTB1/2eff
Ex: 1.443 × 72.8 hr
= 105 hr
ln(1.0) – (0.693/72.8)t
37%
105
Approved Regimen for BEXXAR:
Therapeutic Activity Prescription
(Wahl, et al, J Nucl Med 1998; 39(Suppl):14S-20S)
à (mCi-hr)
TBD (cGy)
131I (mCi) = ------------------ × --------------TresTB (hr)
75 cGy
75 cGy
à = --------------------------------------------------------mass corrected S(TB←TB) (cGy/mCi-hr)
TBD = targeted total body dose (65 cGy or 75 cGy)
Approved Regimen for Zevalin:
www.idecpharm.com/site/science/zevalin.htm
Day 0
• Rituxan (cold antibody) – 250 mg/m2
• 111In-Zevalin (5 mCi in 1.6 mg)
• 2 – 24 hr post-infusion A/P whole body scan (10 cm/min)
Day 2 or 3
• 48 – 72 hr post-infusion A/P whole body scan (7 cm/min)
[Optional] Day 4 or 5
• 90 – 120 hr post-infusion A/P whole body scan (5 cm/min)
Day 7
IF 111In-Zevalin biodistribution is visually normal, THEN:
• Cold antibody (250 mg/m2), then 1.6 mg 90Y-Zevalin
• 0.3 (low platelets) or 0.4 mCi/kg 90Y (≤ 32 mCi)
Approved Regimen for Zevalin:
Simple (but coarse) Dose Estimates
2 hr 111In
47 hr 111In
93 hr 111In
Camera Sensitivity, Swb (assuming 2 hr is pre-voiding)
[CPSwbAnt(2 hr)×CPSwbPost(2 hr)]½ ÷ [Ainj(0) e-.693×2hr/67.9hr]
(Alternative: add a reference source and transmission scans)
Approved Regimen for Zevalin:
Simple (but coarse) Dose Estimates
Ex: Liver estimate
based on all 3 pts,
limited to monoexponential model:
TeffIn-111 = 67.4 hr
TphysIn-111 = 67.9 hr
TphysY-90 = 64.1 hr
GM cps(0) = 294.2
Liver 111In GM ROI cps vs. Time
294.2e-.693t/67.4
1 / TeffY-90 = [ (1/TeffIn-111) – (1/TphysIn-111) ] + (1/TphysY-90)
TresL = GM cps(0) / [Swb×AIn-111(0)] × 1.443 × TeffY-90
DL ≅ AinjY-90(0) × TresL × SY-90L←L × opt. [mRef / mpatient]
Approved Regimen for Zevalin:
2 Point (2 hr, 48 hr) Dose Estimates?
Ex: Liver estimate
based on 1st 2 pts:
TeffIn-111 = 68.2 hr
(> TphysIn-111, which
indicates Zevalin is
biologically on the
increase up to 24 hr!)
GM cps(0) = 293.7
Liver 111In GM cps vs. Time
293.7e-.693t/68.2
Thus, coarse dose estimates based on just 1st 2
points and mono-exponential model will suffice?
A Word About MIRDOSE v 3.1
(© Oak Ridge Associated Universities)
Currently THE accepted standard (e.g., by FDA) for calculating
radiation absorbed doses from internally administered
radiopharmaceuticals, BUT a) only runs on Windows 95/98 (not
NT/2000/XP) and b) is no longer publicly available, so:
• Use previously procured copy of the software (IF you have one)
• ELSE, procure S tables from a colleague who has the software
• ELSE calculate your own S factors!?
• Use radionuclide decay scheme and S factor formula
• Practical only for β- self-dose purposes: Dt = Ãt × Snp(t←t)
• Best case: pure β- emitter w/ simple decay scheme (e.g. 90Y)
• ELSE, see www.doseinfo-radar.com and wait for
OLINDA (≡ next MIRDOSE version, FDA approval pending)
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