Importance of intra-therapy single-photon emission tomographic imaging in calculating tumour dosimetry for a lymphoma patient

The dosimetry for two, similarly sized tumours in a lymphoma patient being treated with non-bone marrow ablative, monoclonal antibody therapy is reported. The 45-year-old man was infused with 2.48 GBq (67 mCi) of 131 I-labelled MB-1. Prior to therapy, a time series of diagnostic conjugate-view images and a radionuclide transmission scan were obtained and processed to obtain time-activity curves. Starting 2 days after the therapeutic infusion of radioactivity, a second conjugate-view time series was obtained. At that time, a quantitative single-photon emission tomography (SPET) acquisition was also carried out. Pre- and post-therapy X-ray computed tomography scans demonstrated a percentage reduction in volume for the right tumour which was 3.8 times that for the left tumour. In contrast, diagnostic conjugate views by themselves estimated the absorbed dose to be the same for the two tumours. Addition of therapy conjugate-view data increased the right-over-left ratio but only to 1.22. Normalizing either time-activity series by the intra-therapy SPET results increased the ratio to greater than 1.5. We assume here that a differential dose is correct according to the differential tumour shirnkage. One can further assume that the largest ratio corresponds most certainly to the most accurate dosimetric method. Other assumptions are possible. While additional study is essential, data from this patient suggest that the preferred dosimetric method is intra-therapy SPET normalization of either time series.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46832/1/259_2005_Article_BF02258433.pd

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

Abstract 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 146-334cGy. 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78152/1/cbr.2008.0568.pd

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 131I treatments were monitored. Tumor dosimetry, enabled by scintigraphy with 131I 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 131I therapies. Dosimetry indicated delivery of 1970 and 2870cGy to the tumor and 35 and 42cGy 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, 131I treatments induced recession of tumor volume. In patients with metastases that concentrate 131I, 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 131I therapies. Therapy may induce prolonged survival in patients with metastases infringing on the brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78102/1/thy.2008.0426.pd

Quantitative autoradiographic evaluation of the influence of protein dose on monoclonal antibody distribution in human ovarian adenocarcinoma xenografts

We studied the effect of monoclonal antibody protein dose on the uniformity of radioiodinated antibody distribution within tumor masses using quantitative autoradiography. Groups ( n = 11–13/group) of athymic nude mice with subcutaneous HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an 125 I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4, using a high or a low protein dose (500 µg or 5 µg). At 6 days post-injection the macroscopic and microscopic intratumoral biodistribution of radiolabeled antibody was determined. The degree of heterogeneity of the labeled antibody distribution within each tumor was quantified and expressed as the coefficient of variation (CV) of the activity levels in serial histological sections. Tumors from mice given the 500-µg protein doses had substantially lower CV values, 0.327±0.027, than did tumors from animals given 5-µg protein doses, 0.458±0.041, ( P = 0.0078), indicating that the higher protein dose resulted in more homogeneous distribution of radioactivity in tumors than did the lower dose. While the percentage of the injected dose reaching the tumor was comparable between groups, injecting the higher dose of protein resulted in significantly lower tumor to non-tumor uptake ratios than those obtained for the lower protein dose. These data indicate, in this system, that to achieve more uniform intratumoral antibody (and radiation for radioimmunotherapy) delivery, a relatively high protein dose must be administered. However, to obtain this increased uniformity, a substantial drop in tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation of human tumor xenografts is a useful method to assess the intratumoral distribution of antibodies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46859/1/262_2005_Article_BF01789014.pd

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

A method for tumor dosimetry based on hybrid planar-SPECT/CT images and semiautomatic segmentation

Purpose: A hybrid planar-SPECT/CT method for tumor dosimetry in 177Lu-DOTATATE therapy, applicable to datasets consisting of multiple conjugate-view images and one SPECT/CT, is developed and evaluated. Methods: The imaging protocol includes conjugate-view imaging at 1, 24, 96, and 168 h post infusion (p.i.) and a SPECT/CT acquisition 24 h p.i. The dosimetry method uses the planar images to estimate the shape of the time–activity concentration curve, which is then rescaled to absolute units using the SPECT-derived activity concentration. The resulting time-integrated activity concentration coefficient (TIACC) is used to calculate the tumor-absorbed dose. Semiautomatic segmentation techniques are applied for tumor delineation in both planar and SPECT images, where the planar image segmentation is accomplished using an active-rays-based technique. The selection of tumors is done by visual inspection of planar and SPECT images and applying a set of criteria concerning the tumor visibility and possible interference from superimposed activity uptakes in the planar images. Five different strategies for determining values from planar regions of interest (ROIs), based on entire or partial ROIs, and with and without background correction, are evaluated. Evaluation is performed against a SPECT/CT-based method on data from six patients where sequential conjugate-view and SPECT/CT imaging have been performed in parallel and against ground truths in Monte Carlo simulated images. The patient data are also used to evaluate the interoperator variability and to assess the validity of the developed criteria for tumor selection. Results: For patient images, the hybrid method produces TIACCs that are on average 6% below those of the SPECT/CT only method, with standard deviations for the relative TIACC differences of 8%–11%. Simulations show that the hybrid and SPECT-based methods estimate the TIACCs to within approximately 10% for tumors larger than around 10 ml, while for smaller tumors, all methods underestimate the TIACCs due to underestimations of the activity concentrations in the SPECT images. The planar image segmentation has a low operator dependence, with a median Dice similarity coefficient of 0.97 between operators. The adopted criteria for tumor selection manage to discriminate the tumors for which the absorbed-dose deviations between the hybrid and SPECT methods are the highest. Conclusions: The hybrid method is found suitable for studies of tumor-absorbed doses in radionuclide therapy, provided that selection criteria regarding the visibility and overlapping activities in the planar images are applied