Whole body retention of I-131 at 24hr vs 48hr as a predictor of maximum tolerated activity.
1. Whole body retention of I-131 at 24hr vs 48hr as a predictor of maximum tolerated activity.
Atkins F1, Van Nostrand D1, Orquiza M1, Wartofsky L2
MedStar Washington Hospital Center, Div of Nuclear Medicine1, Dept of Medicine2
Introduction (cont’d)
References
Discussion
Objective: To evaluate the reliability and robustness of a
single measurement at 24hr post-administration of I-131 of
fractional whole body retention as a predictor of the
Maximum Tolerated Activity (MTA). One advantage of the
24hr over the 48hr time point, if reliable, might be an
extension of this model to I-123 as typically used for pre-
therapy imaging.
Methods: Previously, we reported on a bi-exponential model
to estimate the MTA of I-131 for the treatment of metastatic,
well-differentiated thyroid cancer (WDTC) based on a limit
of 2 Gy to the blood.1 This model uses the patient’s body
surface area (BSA) along with the fractional whole body
retention (WBR) of a diagnostic dosage of I-131 measured
at 48 hrs post oral administration. Since March 2011, all
patients (n=99) undergoing blood based dosimetry also had
their %WBR calculated at 24hr post administration of
approximately 74 MBq of I-131. Patients were prepared
either by thyroid hormone withdrawal (n=41) or recombinant
human thyroid stimulating hormone (rhTSH) (n=58).
Results: A very good correlation exists between the WBR at
24hr and 48hr (r=0.96). Provided the iodine clearance is
relatively rapid (%WBR @ 24hr < 35%), a model based on
this parameter at this time point can be a good predictor of
the MTA (r=0.88). This is more often the case for rhTSH
compared to THW where the median values for the %WBR
at 24hr were 28.9% and 41.8%, respectively.
Conclusions: The WBR at 24hr using I-123 could be used
in a predictive model of the MTA provided this value is
<35%. Otherwise, a delayed measurement at 48hr might be
necessary.
The 24hr time point could be used for this simplified
dosimetry for about half of the patients. For the other
patients, a second measurement at 48hr will still be
necessary.
Introduction
While radioactive iodine has been used in the
treatment of thyroid disease, both benign and malignant, for
over 70 years the decision as to the quantity to be used
continues to remain problematic. Currently this is often
based on a heuristic approach that has been derived from
decades of experience and observations and has resulted
in a set of guidelines or empirically-derived rules for the
treatment of thyroid cancer (e.g. 150-200 mCi [5.55-7.4
GBq] of I-131 is “recommended” in the case of metastatic
mediastinal lymph nodes).
Since these empiric guidelines are based on the
population as a whole and do not account for any other
factors such as age, sex, height, weight, etc. the limits will
necessarily be driven by the worst case scenario. For
example, Kulkarni et al.2 have shown that in a group of
patients being treated for metastatic well-differentiated
Abstract
thyroid carcinoma about 5% of these patients would have
received a radiation dose to their blood that is generally
considered too high based on a standard prescribed activity
of 150 mCi (5.55 GBq). Conversely, it also means that 95%
of these patients could have safely been treated with a
larger quantity of I-131, which in turn, would have delivered
a larger radiation dose to the metastatic tissue being
treated.
An alternative to the empiric guidelines would be a
dosimetric approach based on individualized, patient-
specific measurements of iodine kinetics. While radioactive
iodine has been proven to be very effective at killing normal
and cancerous thyroid tissue, the iodine administered is
unfortunately not just confined to these tissues alone. As a
consequence, other normal organs and tissues will also be
exposed to the radiation from this treatment and can be
potentially damaged as well. Some organs, such as the
bone marrow, are known to be very sensitive to radiation.
Consequently, dosimetry in this context involves the
estimation of the radiation dose that would be delivered to a
given patient’s blood (a surrogate for the bone marrow) due
to the radioiodine therapy.
Unfortunately, dosimetry involves a time and
resource intensive data collection process along with a
moderately complex data analysis. Therefore, a
simplification has been proposed by several authors
whereby the percent whole body retention of I-131 at a
single point in time might be used in a model to estimate an
upper limit of the Maximum Tolerated Activity (MTA) that
could be used for the therapy.3,4
A retrospective, IRB-approved review was conducted
of all thyroid carcinoma dosimetry studies performed on
adult patients (>16 years) at our institution during the
period between Mar 2011 and Dec 2012 (n=99). Patients
were prepared either by thyroid hormone withdrawal
(n=41) or recombinant human thyroid stimulating hormone
(rhTSH) (n=58). The MTA was determined using the Benua
and Leeper5 approach with some minor modifications, and
is based on a maximum tolerated radiation absorbed dose
of 200 rads (cGy) to the blood. The MTA for each patient
was normalized to their body surface area (BSA), which
was calculated based on the Mosteller formula to
compensate for gender and stature differences. As part of
the dosimetry calculation, the whole body retention (WBR)
of a tracer amount of I-131 was obtained at approximately
24-hour intervals. These were normalized to the initial
Methods (cont’d) Results (cont’d)
patients with slow iodine clearance (> 50% retention @ 48hr).
However, as long as the iodine clearance is relatively rapid
(%WBR @ 24hr < 35%) this early time can still be used as a
good predictor of the MTA (r=0.88) as shown in Graph 3.
More often this condition will be satisfied for those patients
who are prepared for their radioiodine therapy using rhTSH
as compared to THW for which the median values for the
%WBR @ 24hr are 28.9% and 41.8%, respectively. Also of
note is that the normalized MTA would appear to have a more
linear rather than exponential relationship to the %WBR over
this range of retention values. Conclusion
This study has multiple limitations. First, the number
of patients was a relatively small group (n=99) of which only
about half met the criterion of %WBR @ 24hr <35%.
Second, more patients need to be analyzed to verify the
regression curve as well as an appropriate threshold (i.e.
70% or 80%) to set in order to avoid overestimating the
amount of I-131 that is safe to use for the patient’s treatment.
Finally, we need to investigate whether or not I-123 can be
used for dosimetry using this simplified methodology.
Methods
1. Van Nostrand D, Atkins F, Moreau S, et al. The utility of
percent 48-hour whole body retention for modifying
empiric amounts of I-131 for the treatment of metastatic
well-differentiated thyroid carcinoma. Thyroid. 2009;
19:1093-1098.
2. Kulkarni K, Van Nostrand D, Atkins F, et al. The
frequency with which empiric amounts of radioiodine
“over-” or “under-” treat patients with metastatic well-
differentiated thyroid cancer. Thyroid. 2006;16:1-5.
3. Sisson J, Shulkin B, Lawson B. Increasing efficacy and
safety of treatments of patients with well-differentiated
thyroid carcinoma by measuring body retentions of 131-
I. J Nucl Med. 2003;44:898-903.
4. Thomas S, Samaratunga R, Sperling M, Maxon H.
Predictive estimate of blood dose from external
counting data preceding radioiodine therapy for thyroid
cancer. Nucl Med Biol. 1993;20:152-163.
5. Benua R, Leeper R. A method and rationale for treating
metastatic thyroid carcinoma with the largest safe dose
of I-131. Frontiers in Thyroidology. 1986;2:1317-1321.
l.
Graph 1. MTA Normalized to Body Surface Area (BSA) as a function of the %WBR
at 48hrs from a previous publication. 1 The solid curves represent the bi-
exponential regression fit to this data. As can be seen, none of the patients’ data
fall below the 70% boundary over this very broad range of %WBR values.
Graph 2. Comparison of the 24hr vs 48hr %WBR based on a log-log relationship. As
can be seen there is a good correlation between these two values.
Graph 3. Linear least squares fit of the %WBR @ 24hr to the normalized MTA. A
reference line at 70% of the “predicted” value does not show any patient that fell
below this point. In fact, there was only one patient that was just below the 80% level.
Results
24hr vs 48hr Reference Time
The 24hr time point, if reliable, would offer some
advantages over the 48hr time point as a predictor of the
MTA. First of all, many of the surveillance studies for
metastatic thyroid cancer performed today use I-123 instead
of I-131 due to its better imaging properties and lower
radiation dose. Unfortunately, it’s short physical half-life (13.5
hrs) makes it less practical to image at 48hr. Secondly,
shortening the time period might allow the patient to receive
his or her radioiodine treatment sooner. Finally this might
potentially allow patients being prepared for their treatment
using rhTSH to avoid a second round of these injections. If
this modification is to be successful, then there needs to be
a well -defined relationship between the %WBR at these two
time points. As can be seen in Graph 2, a very good
correlation does exists between the WBR at 24hr and 48hr
(r=0.96). Since there will always be greater retention at any
earlier time point relative to a later time, this best fit curve
does not intersect the origin as expected.
Even when the 48hr time point is used, it can be seen
from Graph 1 that the model underestimates the MTA for
measurement performed 1-2 hours post-administration to
obtain a percent WBR at each of these time points.
Previously, we reported1 on a bi-exponential model for
estimating the maximum tolerated activity (MTA) of I-131
based on the %WBR at 48hrs which is shown in Graph 1. 1
![Whole body retention of I-131 at 24hr vs 48hr as a predictor of maximum tolerated activity.
Atkins F1, Van Nostrand D1, Orquiza M1, Wartofsky L2
MedStar Washington Hospital Center, Div of Nuclear Medicine1, Dept of Medicine2
Introduction (cont’d)
References
Discussion
Objective: To evaluate the reliability and robustness of a
single measurement at 24hr post-administration of I-131 of
fractional whole body retention as a predictor of the
Maximum Tolerated Activity (MTA). One advantage of the
24hr over the 48hr time point, if reliable, might be an
extension of this model to I-123 as typically used for pre-
therapy imaging.
Methods: Previously, we reported on a bi-exponential model
to estimate the MTA of I-131 for the treatment of metastatic,
well-differentiated thyroid cancer (WDTC) based on a limit
of 2 Gy to the blood.1 This model uses the patient’s body
surface area (BSA) along with the fractional whole body
retention (WBR) of a diagnostic dosage of I-131 measured
at 48 hrs post oral administration. Since March 2011, all
patients (n=99) undergoing blood based dosimetry also had
their %WBR calculated at 24hr post administration of
approximately 74 MBq of I-131. Patients were prepared
either by thyroid hormone withdrawal (n=41) or recombinant
human thyroid stimulating hormone (rhTSH) (n=58).
Results: A very good correlation exists between the WBR at
24hr and 48hr (r=0.96). Provided the iodine clearance is
relatively rapid (%WBR @ 24hr < 35%), a model based on
this parameter at this time point can be a good predictor of
the MTA (r=0.88). This is more often the case for rhTSH
compared to THW where the median values for the %WBR
at 24hr were 28.9% and 41.8%, respectively.
Conclusions: The WBR at 24hr using I-123 could be used
in a predictive model of the MTA provided this value is
<35%. Otherwise, a delayed measurement at 48hr might be
necessary.
The 24hr time point could be used for this simplified
dosimetry for about half of the patients. For the other
patients, a second measurement at 48hr will still be
necessary.
Introduction
While radioactive iodine has been used in the
treatment of thyroid disease, both benign and malignant, for
over 70 years the decision as to the quantity to be used
continues to remain problematic. Currently this is often
based on a heuristic approach that has been derived from
decades of experience and observations and has resulted
in a set of guidelines or empirically-derived rules for the
treatment of thyroid cancer (e.g. 150-200 mCi [5.55-7.4
GBq] of I-131 is “recommended” in the case of metastatic
mediastinal lymph nodes).
Since these empiric guidelines are based on the
population as a whole and do not account for any other
factors such as age, sex, height, weight, etc. the limits will
necessarily be driven by the worst case scenario. For
example, Kulkarni et al.2 have shown that in a group of
patients being treated for metastatic well-differentiated
Abstract
thyroid carcinoma about 5% of these patients would have
received a radiation dose to their blood that is generally
considered too high based on a standard prescribed activity
of 150 mCi (5.55 GBq). Conversely, it also means that 95%
of these patients could have safely been treated with a
larger quantity of I-131, which in turn, would have delivered
a larger radiation dose to the metastatic tissue being
treated.
An alternative to the empiric guidelines would be a
dosimetric approach based on individualized, patient-
specific measurements of iodine kinetics. While radioactive
iodine has been proven to be very effective at killing normal
and cancerous thyroid tissue, the iodine administered is
unfortunately not just confined to these tissues alone. As a
consequence, other normal organs and tissues will also be
exposed to the radiation from this treatment and can be
potentially damaged as well. Some organs, such as the
bone marrow, are known to be very sensitive to radiation.
Consequently, dosimetry in this context involves the
estimation of the radiation dose that would be delivered to a
given patient’s blood (a surrogate for the bone marrow) due
to the radioiodine therapy.
Unfortunately, dosimetry involves a time and
resource intensive data collection process along with a
moderately complex data analysis. Therefore, a
simplification has been proposed by several authors
whereby the percent whole body retention of I-131 at a
single point in time might be used in a model to estimate an
upper limit of the Maximum Tolerated Activity (MTA) that
could be used for the therapy.3,4
A retrospective, IRB-approved review was conducted
of all thyroid carcinoma dosimetry studies performed on
adult patients (>16 years) at our institution during the
period between Mar 2011 and Dec 2012 (n=99). Patients
were prepared either by thyroid hormone withdrawal
(n=41) or recombinant human thyroid stimulating hormone
(rhTSH) (n=58). The MTA was determined using the Benua
and Leeper5 approach with some minor modifications, and
is based on a maximum tolerated radiation absorbed dose
of 200 rads (cGy) to the blood. The MTA for each patient
was normalized to their body surface area (BSA), which
was calculated based on the Mosteller formula to
compensate for gender and stature differences. As part of
the dosimetry calculation, the whole body retention (WBR)
of a tracer amount of I-131 was obtained at approximately
24-hour intervals. These were normalized to the initial
Methods (cont’d) Results (cont’d)
patients with slow iodine clearance (> 50% retention @ 48hr).
However, as long as the iodine clearance is relatively rapid
(%WBR @ 24hr < 35%) this early time can still be used as a
good predictor of the MTA (r=0.88) as shown in Graph 3.
More often this condition will be satisfied for those patients
who are prepared for their radioiodine therapy using rhTSH
as compared to THW for which the median values for the
%WBR @ 24hr are 28.9% and 41.8%, respectively. Also of
note is that the normalized MTA would appear to have a more
linear rather than exponential relationship to the %WBR over
this range of retention values. Conclusion
This study has multiple limitations. First, the number
of patients was a relatively small group (n=99) of which only
about half met the criterion of %WBR @ 24hr <35%.
Second, more patients need to be analyzed to verify the
regression curve as well as an appropriate threshold (i.e.
70% or 80%) to set in order to avoid overestimating the
amount of I-131 that is safe to use for the patient’s treatment.
Finally, we need to investigate whether or not I-123 can be
used for dosimetry using this simplified methodology.
Methods
1. Van Nostrand D, Atkins F, Moreau S, et al. The utility of
percent 48-hour whole body retention for modifying
empiric amounts of I-131 for the treatment of metastatic
well-differentiated thyroid carcinoma. Thyroid. 2009;
19:1093-1098.
2. Kulkarni K, Van Nostrand D, Atkins F, et al. The
frequency with which empiric amounts of radioiodine
“over-” or “under-” treat patients with metastatic well-
differentiated thyroid cancer. Thyroid. 2006;16:1-5.
3. Sisson J, Shulkin B, Lawson B. Increasing efficacy and
safety of treatments of patients with well-differentiated
thyroid carcinoma by measuring body retentions of 131-
I. J Nucl Med. 2003;44:898-903.
4. Thomas S, Samaratunga R, Sperling M, Maxon H.
Predictive estimate of blood dose from external
counting data preceding radioiodine therapy for thyroid
cancer. Nucl Med Biol. 1993;20:152-163.
5. Benua R, Leeper R. A method and rationale for treating
metastatic thyroid carcinoma with the largest safe dose
of I-131. Frontiers in Thyroidology. 1986;2:1317-1321.
l.
Graph 1. MTA Normalized to Body Surface Area (BSA) as a function of the %WBR
at 48hrs from a previous publication. 1 The solid curves represent the bi-
exponential regression fit to this data. As can be seen, none of the patients’ data
fall below the 70% boundary over this very broad range of %WBR values.
Graph 2. Comparison of the 24hr vs 48hr %WBR based on a log-log relationship. As
can be seen there is a good correlation between these two values.
Graph 3. Linear least squares fit of the %WBR @ 24hr to the normalized MTA. A
reference line at 70% of the “predicted” value does not show any patient that fell
below this point. In fact, there was only one patient that was just below the 80% level.
Results
24hr vs 48hr Reference Time
The 24hr time point, if reliable, would offer some
advantages over the 48hr time point as a predictor of the
MTA. First of all, many of the surveillance studies for
metastatic thyroid cancer performed today use I-123 instead
of I-131 due to its better imaging properties and lower
radiation dose. Unfortunately, it’s short physical half-life (13.5
hrs) makes it less practical to image at 48hr. Secondly,
shortening the time period might allow the patient to receive
his or her radioiodine treatment sooner. Finally this might
potentially allow patients being prepared for their treatment
using rhTSH to avoid a second round of these injections. If
this modification is to be successful, then there needs to be
a well -defined relationship between the %WBR at these two
time points. As can be seen in Graph 2, a very good
correlation does exists between the WBR at 24hr and 48hr
(r=0.96). Since there will always be greater retention at any
earlier time point relative to a later time, this best fit curve
does not intersect the origin as expected.
Even when the 48hr time point is used, it can be seen
from Graph 1 that the model underestimates the MTA for
measurement performed 1-2 hours post-administration to
obtain a percent WBR at each of these time points.
Previously, we reported1 on a bi-exponential model for
estimating the maximum tolerated activity (MTA) of I-131
based on the %WBR at 48hrs which is shown in Graph 1. 1](https://image.slidesharecdn.com/atkins24hrwbrvs5-130603001630-phpapp02/85/Whole-body-retention-of-I-131-at-24hr-vs-48hr-as-a-predictor-of-maximum-tolerated-activity-1-320.jpg)
