Yuni K. Dewaraja

MIRD Pamphlet No. 23: Quantitative SPECT for Patient-Specific 3-Dimensional Dosimetry in Internal Radionuclide Therapy

In internal radionuclide therapy, a growing interest in voxel-level estimates of tissue-absorbed dose has been driven by the desire to report radiobiologic quantities that account for the biologic consequences of both spatial and temporal nonuniformities in these dose estimates. This report presents an overview of 3-dimensional SPECT methods and requirements for internal dosimetry at both regional and voxel levels. Combined SPECT/CT image-based methods are emphasized, because the CT-derived anatomic information allows one to address multiple technical factors that affect SPECT quantification while facilitating the patient-specific voxel-level dosimetry calculation itself. SPECT imaging and reconstruction techniques for quantification in radionuclide therapy are not necessarily the same as those designed to optimize diagnostic imaging quality. The current overview is intended as an introduction to an upcoming series of MIRD pamphlets with detailed radionuclide-specific recommendations intended to provide best-practice SPECT quantification–based guidance for radionuclide dosimetry.

131I-Tositumomab Radioimmunotherapy: Initial Tumor Dose–Response Results Using 3-Dimensional Dosimetry Including Radiobiologic Modeling

For optimal treatment planning in radionuclide therapy, robust tumor dose–response correlations must be established. Here, fully 3-dimensional (3D) dosimetry was performed coupling SPECT/CT at multiple time points with Monte Carlo–based voxel-by-voxel dosimetry to examine such correlations. Methods: Twenty patients undergoing 131I-tositumomab for the treatment of refractory B-cell lymphoma volunteered for the study. Sixty tumors were imaged. Activity quantification and dosimetry were performed using previously developed 3D algorithms for SPECT reconstruction and absorbed dose estimation. Tumors were outlined on CT at multiple time points to obtain absorbed dose distributions in the presence of tumor deformation and regression. Equivalent uniform dose (EUD) was calculated to assess the biologic effects of the nonuniform absorbed dose, including the cold antibody effect. Response for correlation analysis was determined on the basis of the percentage reduction in the product of the largest perpendicular tumor diameters on CT at 2 mo. Overall response classification (as complete response, partial response, stable disease, or progressive disease) used for prediction analysis was based on criteria that included findings on PET. Results: Of the evaluated tumor-absorbed dose summary measures (mean absorbed dose, EUD, and other measures from dose-volume histogram analysis), a statistically significant correlation with response was seen only with EUD (r = 0.36 and P = 0.006 at the individual tumor level; r = 0.46 and P = 0.048 at the patient level). The median value of mean absorbed dose for stable disease, partial response, and complete response patients was 196, 346, and 342 cGy, respectively, whereas the median value of EUD for each of these categories was 170, 363, and 406 cGy, respectively. At a threshold of 200 cGy, both mean absorbed dose and EUD had a positive predictive value for responders (partial response + complete response) of 0.875 (14/16) and a negative predictive value of 1.0 (3/3). Conclusion: Improved dose–response correlations were demonstrated when EUD incorporating the cold antibody effect was used instead of the conventionally used mean tumor-absorbed dose. This work demonstrates the importance of 3D calculation and radiobiologic modeling when estimating absorbed dose for correlation with outcome.

3D absorbed dose calculations based on SPECT: Evaluation for 111-In/90-Y therapy using Monte Carlo simulations

A general method is presented for patient-specific three-dimensional (3D) absorbed dose calculations based on quantitative SPECT activity measurements. The computational scheme includes a method for registration of the CT study to the SPECT image, and compensation for attenuation, scatter, and collimator-detector response including septal penetration, performed as part of an iterative reconstruction method. From SPECT images, the absorbed dose rate is calculated using an EGS4 Monte Carlo code, which converts the activity distribution to an absorbed dose rate distribution. Evaluation of the accuracy in the activity quantification and the absorbed dose calculation is based on realistic Monte Carlo simulated SPECT data of a voxel-computer phantom and (111)In and (90)Y. Septal penetration was not included in this study. The SPECT-based activity concentrations and absorbed dose distributions are compared to the actual values; the results imply that the corrections for attenuation and scatter yield results of high accuracy. The presented method includes compensation for most parameters deteriorating the quantitative image information. Inaccuracies are, however, introduced by the limited spatial resolution of the SPECT system, which are not fully compensated by the collimator-response correction. The proposed evaluation methodology may be used as a basis for future inter-comparison of different dosimetry calculation schemes.

MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy

The accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet no. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on 177Lu (lutetium) and its application in radiopharmaceutical therapy.

MIRD Pamphlet No. 24: Guidelines for Quantitative 131I SPECT in Dosimetry Applications

The reliability of radiation dose estimates in internal radionuclide therapy is directly related to the accuracy of activity estimates obtained at each imaging time point. The recently published MIRD pamphlet no. 23 provided a general overview of quantitative SPECT imaging for dosimetry. The present document is the first in a series of isotope-specific guidelines that will follow MIRD 23 and focuses on one of the most commonly used therapeutic radionuclides, 131I. The purpose of this document is to provide guidance on the development of protocols for quantitative 131I SPECT in radionuclide therapy applications that require regional (normal organs, lesions) and 3-dimensional dosimetry.

A parallel Monte Carlo code for planar and SPECT imaging: implementation, verification and applications in 131I SPECT

This paper reports the implementation of the SIMIND Monte Carlo code on an IBM SP2 distributed memory parallel computer. Basic aspects of running Monte Carlo particle transport calculations on parallel architectures are described. Our parallelization is based on equally partitioning photons among the processors and uses the Message Passing Interface (MPI) library for interprocessor communication and the Scalable Parallel Random Number Generator (SPRNG) to generate uncorrelated random number streams. These parallelization techniques are also applicable to other distributed memory architectures. A linear increase in computing speed with the number of processors is demonstrated for up to 32 processors. This speed-up is especially significant in Single Photon Emission Computed Tomography (SPECT) simulations involving higher energy photon emitters, where explicit modeling of the phantom and collimator is required. For (131)I, the accuracy of the parallel code is demonstrated by comparing simulated and experimental SPECT images from a heart/thorax phantom. Clinically realistic SPECT simulations using the voxel-man phantom are carried out to assess scatter and attenuation correction.

Quantitative /sup 131/I SPECT with triple energy window Compton scatter correction

In this work accuracy of quantitative /sup 131/I SPECT with triple energy window (TEW) scatter correction is evaluated by phantom measurements. The application is tumor imaging of B-cell lymphoma patients treated with /sup 131/I radioimmunotherapy. The TEW method is a pixel by pixel correction where the scatter fraction in the photopeak window is estimated by linear interpolation between two adjacent narrow sub-windows. For the phantom measurements performed in this work the TEW estimate of scattered counts was close to one half of the total photopeak window counts. Quantification procedure includes marker based X-ray CT-SPECT image fusion to determine object boundaries and to generate attenuation maps. TEW scatter correction significantly reduces the effect of background activity on reconstructed counts within an object, but it still exists due to the finite spatial resolution of the system. Therefore, a background dependent calibration factor had to be used to achieve good quantitative accuracy. Quantitative accuracy with TEW correction was 5% and 14% for a tumor and lung respectively of a physical phantom with non-uniform activity and non-uniform scattering medium. With no scatter subtraction but using a background dependent calibration the quantitative accuracy was 7% and 18% for the tumor and lung respectively.

Thyroid Carcinoma Metastasis to Skull with Infringement of Brain: Treatment with Radioiodine

BACKGROUND Infringement by differentiated thyroid carcinoma on the brain is rare but, when suspected, the patient deserves special attention. A patient with an enlarging metastasis of thyroid carcinoma to the skull that was impinging on the brain illustrates diagnostic and therapeutic strategies applicable to the treatment of metastatic carcinoma. METHODS A case study was performed. Computed tomography (CT) and magnetic resonance imaging (MRI) were done, serum thyroglobulin was measured, and tumor responses to thyroxine and (131)I treatments were monitored. Tumor dosimetry, enabled by scintigraphy with (131)I employing single photon emission tomography fused with CT (SPECT-CT), was performed. RESULTS The metastasis was from a follicular variant of papillary thyroid carcinoma. During thyrotropin stimulation the tumor enlarged. The tumor decreased in volume after each of two (131)I therapies. Dosimetry indicated delivery of 1970 and 2870 cGy to the tumor and 35 and 42 cGy to the brain, respectively, in the two treatments. The patient has survived for more than 11 years since diagnosis. CONCLUSIONS A metastasis from a follicular variant of papillary carcinoma increased in volume during hypothyroidism producing more infringement on the brain. Beyond the effects of thyroxine therapy, (131)I treatments induced recession of tumor volume. In patients with metastases that concentrate (131)I, dosimetry with SPECT-CT can predict absorbed doses of radiation to the tumor and to the adjacent organs and thus lay a basis for data-based decisions on (131)I therapies. Therapy may induce prolonged survival in patients with metastases infringing on the brain.

Use of Integrated SPECT/CT Imaging for Tumor Dosimetry in I-131 Radioimmunotherapy: A Pilot Patient Study

Integrated systems combining functional (single-photon emission computed tomography; SPECT) imaging with anatomic (computed tomography; CT) imaging have the potential to greatly improve the accuracy of dose estimation in radionuclide therapy. In this article, we present the methodology for highly patient-specific tumor dosimetry by utilizing such a system and apply it to a pilot study of 4 follicular lymphoma patients treated with I-131 tositumomab. SPECT quantification included three-dimensional ordered-subset expectation-maximization reconstruction and CT-defined tumor outlines at each time point. SPECT/CT images from multiple time points were coupled to a Monte Carlo algorithm to calculate a mean tumor dose that incorporated measured changes in tumor volume. The tumor shrinkage, defined as the difference between volumes drawn on the first and last CT scan (a typical time period of 15 days) was in the range 5%-49%. The therapy-delivered mean tumor-absorbed dose was in the range 146-334 cGy. For comparison, the therapy dose was also calculated by assuming a static volume from the initial CT and was found to underestimate this dose by up to 47%. The agreement between tracer-predicted and therapy-delivered tumor-absorbed dose was in the range 7%-21%. In summary, malignant lymphomas can have dramatic tumor regression within days of treatment, and advanced imaging methods allow for a highly patient-specific tumor-dosimetry calculation that accounts for this regression.

Recovery of total I-131 activity within focal volumes using SPECT and 3D OSEM

We experimentally investigated the SPECT recovery of I-131 activity in multiple spheres located simultaneously at different locations within a cylindrical phantom that had an elliptical cross section. The sphere volumes ranged from 209 cc down to 4.2 cc. A Prism 3000 camera and two types of parallel-hexagonal-hole collimation were employed: high energy (HE) and ultra high energy (UHE). Using appropriately-different 3D models of the point source response function for the two types of collimation, approximately the same recovery of activity could be achieved with either collimation by 3D OSEM reconstruction. The recovery coefficient was greater with no background activity in the phantom by 0.10, on average, compared to that with background. In the HE collimation case, the activity recovery was considerably better for all volumes using 3D OSEM reconstruction than it had been in the past using 1D SAGE reconstruction. Recovery-coefficient-based correction in a simulated patient case involving spherical tumours moderately improved the activity estimates (average error reduced from 14% to 9% for UHE collimation, and from 15% to 11% for HE collimation). For a test case with HE collimation, increasing the projection-image sampling density while decreasing the image voxel size increased the recovery coefficient by 0.075 on average, and, if used in a full set of calibration measurements of recovery coefficient versus volume, might lead to further improvement in accuracy for the patient case.