Trial Information

Comparison of I-124 and I-131 Radiopharmacokinetics in Patients Who Have Well-differentiated Thyroid Cancer and Are Prepared With Recombinant Human TSH Injection (rhTSH)

Radiopharmacokinetics and Dosimetric Calculations

A tracer dosage of either I-131 or I-124 is first administered to the patient, and the
clearance is then followed for the specified period. In the classical approach, the blood is
considered the critical organ which is irradiated either from the

- particles emitted from activity in the blood itself, or from the

- emissions originating from activity dispersed throughout the remainder of the body.
Therefore only two compartments need to be monitored for radioactivity: (a) blood and
(b) the whole body. Based on a classical dosimetry approach, the radiation dose to the
whole blood in cGy (rads) per MBq I-131 is calculated.

The calculation of the area under these two curves is based on a mathematical fit to the
data points using a multiple exponential function. Since the data collection is terminated
after 4 days these curves must then be extrapolated to infinity. A very conservative
estimate is employed by assuming that the clearance following the final measured data point
is based simply on the physical decay. This ignores any biological clearance and results in
an overestimation of the area of these tails and hence in the radiation dose per millicurie
administered.

Each patient will have the following calculated.

i. Whole body radiopharmacokinetics

ii. Blood radiopharmacokinetics

iii. Whole blood dosimetry

iv. Lesion Kinetics

i. Whole body radiopharmacokinetics

As an alternative to using an external probe to measure the whole body retention, a dual
detector gamma camera system can be used. In this case the patient is scanned in the whole
body mode in a reproducible geometry while lying supine on the imaging table. This method
has been generally accepted for patient-specific whole body dosimetry of I-131 radiolabeled
antibodies . Furthermore, it has been shown to yield comparable results with the external
probe data . This technique has the following features:

- Simultaneous anterior and posterior images using a high-energy collimator.

- Table height, detector radii, scan length, scan speed, and energy window are
standardized and reproduced for each data point.

- Scan speed can be relatively rapid (typically we have used 30 cm/min) so that the data
acquisition is completed in approximately 8 minutes.

- Additional scans are performed each day for (1) background, and (2) a counting standard
(vial containing about 37 MBq (1 mCi) of I-131).

- Total counts in the image or fixed regions of interest encompassing the entire body are
used for the calculation of whole body retention.

Although the images are not used for diagnostic purposes, this approach has the additional
advantage that if for some reason there is delayed absorption of the tracer dosage in the
stomach, and then the measurement could be repeated at 4 hours.

During the initial 2-hour period following the I-131 administration the patient is not
allowed to urinate or defecate. Under these circumstances essentially 100 percent of the
dosage will be contained within the patient at these observation points. The initial image
is then defined to represent the 100 percent value and subsequent daily measurements are
normalized to this value using the formula:

When used in this way, the standard will correct for variations in detector sensitivity from
measurement to measurement, as well as for physical decay. Absolute calibrations are not
necessary since the patient is used as his/her reference.

The whole body I-124 images will be obtained at the same time points using the PET system.
In this case emission imaging will be obtained for 1-2 minutes/bed position for a sufficient
number of positions to cover the patient from head to foot. Transmission imaging will also
be performed to correct the emission data for attenuation.

ii. Blood pharmacokinetics

The blood samples (3-4 ml in purple top tubes) are counted using scintillation well-detector
system. Since we need to determine the activity in these samples, it is necessary to make
up a calibration standard, which can be counted at the same time. This involves the
addition of a carefully assayed quantity of I-131 (approximately 3.7 MBq - 7.4 MBq {100-200
uCi}) to a total volume of 1000 ml. Such a small concentration is necessary in order to
avoid saturating the detector. An alternative that we have implemented in the dosimetry
program here at the Washington Hospital Center uses a Ba-133 rod source instead that has
been cross-calibrated against the I-131 standard. With its relatively long half-life (10.3
years) and similar gamma emissions, Ba-133 is a suitable replacement for the prepared I-131
standard. At the conclusion of the data acquisition, two 1-ml aliquots of whole blood, and
the "standard" are counted. Using this information, it is possible to calculate the % of
administered dosage/liter of whole blood at each of the timed samples. A zero time point is
calculated by dividing the total dosage by the patient's total blood volume. However, a
patient-specific blood volume is not determined, but is assumed to equal 20% of the body
weight.

iii. Whole blood dosimetry

The Maximum Treatment Activity (MTA) is then calculated as the activity of I-131, which
would deliver a combined beta and gamma dose to the blood component of 200 cGy (200 rads).

This calculation will be performed using the whole body and blood clearance data from both
the I-131 and the I-124 biokinetic clearance data. The I-124 data will first be corrected
for the difference in half-lives of these two radionuclides so as to generate the
"equivalent" I-131 values.

iv. Lesion Kinetics

For those patients in which focal lesion(s) can be visualized the clearance curves and
half-lives will be determined from the images for both the I-131 and the I-124 studies. A
manually drawn region-of interest (ROI) will be placed around each lesion as visualized on
the diagnostic whole body scan performed at 48hrs post administration of the radioiodine.
This ROI will then be positioned over the comparable area on each of the scans. A
background ROI adjacent to the lesion will also be drawn. The total counts in the lesion
after background correction will be determined for each time point. In the case of the PET
scans first each PET study will be co-registered to the diagnostic scan using the Hermes
image registration tool. The coronal slices will then be added to generate a whole body
scan that is "equivalent" to that of I-131. Regions of interest will be defined in the same
manner as discussed above. A least squares single exponential fit will be applied to each
of the lesion clearance curves. The half-life of the exponential will then be computed and
the values derived for I-131 compared with I-124 for each identified lesion.