Year 9, Number 36, April 2007

 

Optimization of Ablative Dose for Thyroid Cancer

 

 

Materials and Methods


Nine patients were studied, all female, between 26 and 73 years of age, who came to the Sector of Nuclear Medicine for evaluation in order to perform ablation of thyroid remnant tissue after surgery at least 40 days earlier. Patients were treated following the usual routines of the center, with administration of approximately 148 MBq (4 mCi) of 131I to perform a biokinetic and anatomic study with SPECT. Images were made at 2-4 h, 24 h, 48 h and 72 h after administration. The images made at 2-4 hours post administration were needed to establish the uptake phase in the thyroid tissue, which occurs during the first 24 hours. Images were made with a commercial gamma camera (General Electric Medical System - STARCAM 2000) equipped with a high energy collimator. Image processing was performed on an ADAC-Pegasys workstation. Acquisition and image reconstruction parameters were as described by Lima et al. 4.

Calculation of Tissue Volume

Thyroid tissue volume was determined for each patient from the imate data; the volume of the remnant tissue used in the calculations was the largest value observed on the four images taken. After image processing, the calculated volumes were compared with the expected volumes, based on the difference between the standard volume of a normal thyroid (15-20 ml) and the volume of tissue removed during surgery, as determined during pathology examinations. As a further check on these calculations, images of each patient were transformed into GIF images and digitized with a program called SCMS (ref), developed to act as the interface between medical images (CT, SPECT or PET) and the Monte Carlo radiation transport code MCNP 5. One of the modules of this code (SETUP) has a routine which can divide the volume of an organ into small regions. Then, the number of voxels in each region can be determined, and, knowing the size of each voxel (2.9 mm cube) the volume of the thyroid remnant tissue can be calculated analytically for each subject.

Determination of 131I Concentration

Using the reconstructed images, count densities were determined using Region-of-Interest (ROI) analyses in each slice of the image data, with the total count density determined as the sum of th densities in each slice, using calibration factors determined for the system (MBq/mL) (Lima et al. 4). Knowing the activity concentration for each patient, we calculated the activity of 131I in the thryoid remants at the time of image acquisition. Thus the activity was calculated as the product of the activity concentration and the tissue volume.

Calculation of Optimal Therapeutic Activity

Activity values determined for each patient were plotted, and the uptake and elimination phases were fit to a two component exponential function using the Grace - 5.0 code. The fitted function was thus of the form:

 

 y(t) = a0 . (e-a1 t - e-a2 t)   

     (2)

                         

where y(t) is the activity in the thyroid at any time, and a0, a1, and a2 are fitted parameters. The cumulated activity is obtained by direct integration of equation (2), and the maximum activity in the thyroid is given as:

 Amáx = f . A0 = a0 . C   

    (3)

                        

where f is the maximum fraction of administered activity (A0) in the thyroid and C = [(a2 / a1)-a1/ (a2 / a1) - (a2 / a1)-a2/ (a2 - a1) ].

The standard dose equation for average dose in an organ is given as:

 D =
ÃhΣ Δi. Φi   
————

m
(4) 

where m is the mass of the remnant thyroid tissue. Thus, the activity that should be administered to any subject is calculated as:

A0 =
C . a1 . a2 . D . m ,  
—————————

f . (a2-a1) . Δβ
(5) 

where Δβ for 131I is 3.07 x 10-14 Gy.kg/Bq.s.

Computer Program for Dose Planning

To facilitate the implementation of the above considerations in routine nuclear medicine practice, we created a compute program, called PlanDose, which provides the optimum therapeutic activity of 131I to be administered to a patient, given the input of appropriate data. The program was written in C, which allows for flexibility and portability on many platforms when compiled. Users must enter data from the biokinetic study for a subject, and the program fits the data to the function shown in Eq. (2), using a Figure of Merit analysis (χi2)1:

χi2 = Σi [yi – f(xi)]2,  

(7) 

where, yi is a measurement-dependent variable and f(xi) is the value of the variable which depends on the point x in the model. The variables a0, a1 and a2 are obtained through fitting and minimization of this function. To treat a nonlinear function, the minimization is done through an iterative (Levenberg-Marquardt) model. The minimization criteria are that (χ2i2i+1)2 < 0,001 or N = 40 where N is the number of iterations. These values were selected to limit the time needed to fit the data using Grace 5.0. Then, once the fitted coefficients of the time-activity curve are obtained, the maximum thyroid uptake and therapeutic activity needed for the subject are calculated according to equations (3) and (5).

 


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