Joshua Grimes

Patient-Specific Radiation Dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in Neuroendocrine Tumors

99mTc-hydrazinonicotinamide-Tyr3-octreotide (99mTc-HYNIC-TOC) is increasingly gaining acceptance as a new radiopharmaceutical for the diagnosis of pathologic lesions overexpressing somatostatin receptors. However, little information has been published about the radiation dosimetry of this agent. The aim of this study was to assess the biodistribution and radiation dosimetry of commercially available 99mTc-HYNIC-TOC. A dose calculation procedure designed to be feasible to implement in a busy clinical environment was used. Methods: Twenty-eight patients were imaged for suspected neuroendocrine tumors using a series of whole-body planar, dynamic planar, and SPECT/CT studies, after injection with 99mTc-HYNIC-TOC. Patient-specific dosimetry was performed using the OLINDA/EXM software with time-integrated activity coefficients estimated from a hybrid planar/SPECT technique. A phantom experiment was performed to establish adaptive thresholds for determination of source region volumes and activities. Results: Pathologic uptake, diagnosed as due to neuroendocrine tumors, was observed in 12 patients. Normal organs with significant uptake included the kidneys, liver, and spleen. The mean effective dose after 99mTc-HYNIC-TOC injection was 4.6 ± 1.1 mSv. Average normal-organ doses were 0.030 ± 0.012, 0.021 ± 0.007, and 0.012 ± 0.005 mGy/MBq for the spleen, kidneys, and liver, respectively. The interpatient kidney dose ranged from 0.011 to 0.039 mGy/MBq, whereas the range of tumor doses varied from 0.003 to 0.053 mGy/MBq. The ratio of tumor to kidney dose ranged from 0.13 to 2.9. The optimal thresholds for recovery of true activity in the phantom study were significantly lower than those used for volume determination. Conclusion: The patient-specific 3-dimensional dosimetry protocol used in this study is a clinically feasible technique that has been applied to demonstrate large dose variations in tumors and normal organs between patients imaged with 99mTc-HYNIC-TOC.

Theoretical dosimetry estimations for radioisotopes produced by proton-induced reactions on natural and enriched molybdenum targets

This study presents a summary of the dosimetry calculations performed for three technetium agents most commonly used in nuclear medicine diagnostic studies, namely sestamibi™, phosphonates and pertechnetate, labeled with cyclotron-produced technetium. Calculated patient doses were compared to those that would be delivered by the same radiotracers labeled with technetium obtained from a generator produced in a reactor. The main difference is that technetium from a generator is pure, i.e. contains only (99m)Tc and its decay product (99g)Tc, while in a cyclotron a large number of other stable and radioactive isotopes are created. In our calculations only technetium radioisotopes (ground and isomeric states) were considered as they will be included in the radiotracer labeling process and will contribute to the patient dose. Other elements should be removed by chemical purification. These dose estimates are based on our theoretical calculations of the proton-induced reaction cross sections and radioisotope production yields. Thick targets of enriched (three different compositions) and natural molybdenum, and three initial beam energies (16, 19 and 24 MeV) were considered for irradiation times of 3, 6 and 12 h with a beam current of 200 µA. The doses were calculated for injection times corresponding to 0, 2, 8, 12 and 24 h after the end of beam.

The accuracy and reproducibility of SPECT target volumes and activities estimated using an iterative adaptive thresholding technique.

Objective Our aim was to design a practical and reproducible image segmentation method for calculations of total absorbed doses in organs and tumours for internally delivered radioisotopes. We have built upon our previously proposed use of two separate thresholds and employed an iterative technique for semiautomatic selection of background regions for segmenting an object of interest using thresholds that depend on the source-to-background ratio of activity concentrations. Methods The parameters of curves relating volume and activity thresholds to source-to-background ratio were established using phantoms with 20 different inserts. The accuracy of our technique was validated using a second phantom experiment, whereas the reproducibility of volume, activity and dose estimates of organs and tumours was investigated using 13 patient studies. The accuracy and reproducibility of segmentations achieved were assessed using images reconstructed with three different methods that ranged from a standard clinical reconstruction to an advanced quantitative reconstruction approach. Results In the validation phantom experiment, bottle volumes and activities measured using iterative adaptive thresholding agreed on average with the true values to within 4%, regardless of the reconstruction method used. In the patient studies, volumes and activities estimated from the single-photon emission computed tomography images reconstructed with clinical software agreed with the volumes and activities estimated using the advanced reconstruction approach to within 6%, whereas the corresponding doses agreed to within 4%. Conclusion The proposed iterative adaptive thresholding technique can accurately determine object volume and activity, which allows standard clinical reconstructions to generate absorbed dose estimates that are similar to those values obtained using more advanced reconstruction methods.

JADA: A graphical user interface for comprehensive internal dose assessment in nuclear medicine

PURPOSE The main objective of this work was to design a comprehensive dosimetry package that would keep all aspects of internal dose calculation within the framework of a single software environment and that would be applicable for a variety of dose calculation approaches. METHODS Our MATLAB-based graphical user interface (GUI) can be used for processing data obtained using pure planar, pure SPECT, or hybrid planar/SPECT imaging. Time-activity data for source regions are obtained using a set of tools that allow the user to reconstruct SPECT images, load images, coregister a series of planar images, and to perform two-dimensional and three-dimensional image segmentation. Curve fits are applied to the acquired time-activity data to construct time-activity curves, which are then integrated to obtain time-integrated activity coefficients. Subsequently, dose estimates are made using one of three methods. RESULTS The organ level dose calculation subGUI calculates mean organ doses that are equivalent to dose assessment performed by OLINDA/EXM. Voxelized dose calculation options, which include the voxel S value approach and Monte Carlo simulation using the EGSnrc user code DOSXYZnrc, are available within the process 3D image data subGUI. CONCLUSIONS The developed internal dosimetry software package provides an assortment of tools for every step in the dose calculation process, eliminating the need for manual data transfer between programs. This saves times and minimizes user errors, while offering a versatility that can be used to efficiently perform patient-specific internal dose calculations in a variety of clinical situations.

Personalized Image-Based Radiation Dosimetry for Routine Clinical Use in Peptide Receptor Radionuclide Therapy: Pretherapy Experience

Patient-specific dose calculations are not routinely performed for targeted radionuclide therapy procedures, partly because they are time consuming and challenging to perform. However, it is becoming widely recognized that a personalized dosimetry approach can help plan treatment and improve understanding of the dose-response relationship. In this chapter, we review the procedures and essential elements of an accurate internal dose calculation and propose a simplified approach that is aimed to be practical for use in a busy nuclear medicine department.

Two methods to generate templates for template-based partial volume effect correction: SPECT phantom experiments

In this paper, we explore the applicability of template-based compensation for the partial volume effect (PVE) for situations where (i) the image has multiple uptake sites (tumors and organs) but only one of them is treated as a region of interest (ROI) with the boundaries available from a high-resolution modality and (ii) no information regarding activities inside or outside this ROI is a priori available. We modeled this situation by performing SPECT acquisitions of phantoms containing 21 containers, which had different shapes and sizes and were filled with different levels of activity. In our analysis, each of these containers was treated as an individual ROI. We compared the performance of two methods of template construction. In method 1, the ROI template value was obtained from a conventionally reconstructed (without PVEC) image. In method 2, the ROI template value was directly (bypassing the PVE-affected conventional image) calculated from projections using region-based reconstruction. Our processing shows that method 1 resulted in consistent (activities for all 21 ROIs were improved) but relatively weak PVE compensation (errors of recovered total activities were equal to or lower than 10% for 5 ROIs only). Application of method 2 resulted in a selective (activities for 19 ROIs were improved) but considerably better compensation when compared to method 1 (errors of recovered total activities were equal to or lower than 10% for 10 ROIs).

An adaptive generation of a digital mask to improve activity distribution in SPECT images

In this study, we consider the clinical situation where only the boundaries of the investigated region of interest (ROI) are available and the remaining part of the studied object (background) is inhomogeneous. Additionally, no information regarding activity concentrations in either ROI or background is available. Under such circumstances, which are typical for clinical SPECT and PET oncology studies, accurate recovery of the activity distribution inside the ROI represents a challenging task. Especially, in mask-based partial volume effect (PVE) corrections (PVEC), the digital mask should adequately reflect the true activity distribution. In this respect, the direct implementation of the mask values from the conventionally reconstructed (and, obviously, degraded by PVE) image may affect the accuracy of the resulting activity distribution. In this paper, we present a modification of the mask-based approach where the mask values in the ROI are neither a priori known nor taken from the conventional image, but are determined from the projection data by a special ROI-based algorithm. Because case-specific acquisition parameters, attenuation map, and the projection dataset are employed there, the created mask appears to be adapted to the analyzed SPECT or PET study. Our data processing begins with the segmentation step dividing the scanned object into an ROI and a background. Then, the regional system matrices reflecting the contributions of (i) the ROI and (ii) the background to the projection dataset are computed. These matrices allow us to generate the system of equations from which the average activity concentrations in the ROI and background are derived. We incorporate the average ROI activity concentration into our mask by assigning it to each voxel inside this ROI. At the same time, the mask values for the inhomogeneous background are copied directly from the conventional image. Finally, the mask-based PVEC is applied to recover the activity distribution in the ROI. We validated our method using both a physical phantom experiment and analytical simulations, which in both cases contained 21 active and cold inserts. The performance of the proposed adaptive method was compared with the image-based PVEC where the mask values inside the ROI were calculated based on the conventional image. In terms of recovery of the total activity, the adaptive method outperformed the image-based PVEC for 19 (simulations) and for 20 (physical experiments) out of 21 considered containers. In terms of recovery of the activity distribution, results of the adaptive method were better than ones provided by imagebased PVEC for 16 (simulations) and for 13 (experiments) out of 17 considered containers.

MO‐F‐110‐08: Yields and Dosimetry Estimates for Radioisotopes Produced in Proton‐Induced Reactions on Enriched Molybdenum Targets

Purpose: To investigate radiationdosimetry for 99mTc produced by medical cyclotrons, based on theoreticalreaction cross‐sections and yields. Several other technetiumisotopes produced in a cyclotron are chemically inseparable from 99mTc. This could increase patient absorbed dose. We compared the resulting doses to those from 99mTc produced by conventional 99Mo/99mTc generators. Methods: We simulated natural and enriched molybdenum thick targets irradiated by 10–30MeV protons. All reaction channels leading to any given reaction product were considered in final yields. The cross‐section calculations were performed using the EMPIRE code. A computer graphical user interface for automatic calculation of isotope yields and activities was created. The pertechnetate, phosphonate as well as MIBI radiation absorbed doses were calculated by OLINDA/EXM 1.1 using the adult male reference. Generator produced 99mTc was assumed to have 100% radionuclide purity. Results: The thick target yields for 99mTc, 99gTc and other isotopes were determined for 16‐ 10MeV, 19‐10MeV and 24‐10MeV energy protons. The difference of radiation doses between pure‐Tc (reactor produced) and mixture‐Tc (cyclotron produced) in main organs were estimated. In highly enriched targets (99.5% 100Mo), the mixture‐Tc doses are about 0.5% larger than the pure‐Tc doses. These differences decreased in the first few hours from the end of beam (EOB) and then increased to 1 % after 24 hours from EOB. In targets with lower enrichment (97.4% 100Mo), the 0–8 hours after EOB doses from the mixture‐Tc isotopes exceeded the pure‐99mTc dose by ∼1% or less. For radiopharmaceuticals injected in patients 24 hours after EOB, this difference increased to 2–5%. Conclusion: Other radioisotopes, which will be produced in the cyclotron together with 99mTc must be considered for their potential to increase patient dose exposure. The differences between the radiation absorbed doses from technetium produced by cyclotrons and nuclear reactors are minimal at EOB, and increase slightly after 24 hours.

SU‐E‐J‐128: The Accuracy of Source Region Volume and Activity Estimates from SPECT/CT Imaging for Use in Internal Dose Calculations

Purpose: The aim of this study was to investigate the accuracy of volume and activity estimates derived from single photon emission computed tomography(SPECT)images using methods practical for clinical use in dose calculations for targeted radionuclide therapy. Methods: Five patients with suspected neuroendocrine tumours were injected with ∼900 MBq of Tc‐99m‐Tektrotyd and a SPECT/CT scan was acquired. A phantom experiment was performed to establish an adaptive threshold curve, allowing for the optimal choice of segmentation threshold based on the source‐to‐background ratio of activity. The SPECTimages were reconstructed using a standard clinical reconstruction with attenuation correction (AC). Additionally, an advanced reconstruction method was applied that included AC, resolution recovery and scatter correction. Source regions were segmented in the SPECTimages using three different thresholds: 1) 40%, as commonly used in the literature, 2) the adaptive threshold for true volume estimation (ThV), and 3) the adaptive threshold for true activity determination (ThA). Results: Using the fixed 40% threshold, organ volume estimates from the clinical reconstruction exceeded the advanced reconstruction estimates by 32.4% +/− 23.9% on average. When ThV was applied this difference in volume estimation improved to −2.5% +/− 9.1%. Visual inspection of the SPECT derived organ contours drawn on the CT slices confirmed that ThV organ segmentation corresponded to the true organ boundaries. Activity in regions segmented using ThA was on average 23% greater than activity inside the same regions delineated using ThV, highlighting the importance of using ThA to recover activity blurred out of the regions true volume in the SPECTimages. Conclusions: Adaptive thresholding can be used to accurately obtain source region volume and activity estimates from clinical reconstructions. This provides a clinically feasible alternative to obtaining these estimates from imagesreconstructed using time consuming, advanced methods or from manually delineating regions slice by slice on CT.

Sci-Thurs AM: YIS-05: Accuracy of Patient-Specific Dosimetry for Clinical Use in Targeted Radionuclide Therapy

Introduction: Targeted radionuclide therapy (TRT) uses radiopharmaceuticals that target tumourtissue, potentially delivering large radiationdoses to tumours, while minimizing the dose to surrounding healthy tissue. In this work we investigated how various approximations affect the accuracy of patient‐specific dose calculations in TRT. Methods: Time‐activity curves (TACs) were acquired from a series of nuclear medicineimages, including one SPECT/CT image and multiple planar scans in two patients. Biodistribution of radiopharmaceutical was modeled using: an exponential fit, trapezoidal areas, and without the use of a long term scan to draw the TACs. Cumulated activities (area under TACs) were determined and used in three different dose calculation methods: OLINDA/EXM code, MIRD voxelized S‐values (MVSV), and Monte Carlo simulation (MCS), considered here as the gold standard. Results: Different methods for drawing TACs showed that resulting areas under the curve differ by up to a factor of 4. For dose calculation, OLINDA and MVSV doses differed from the average MCSdose by 5% and 3% respectively. OLINDA does not provide details of dose distribution throughout the tumour, whereas MVSV does. The drawback of MVSV is that it assumes a source material of uniform density. Conclusions: An accurate determination of the TAC is essential for proper dosimetry. Both the OLINDA code and MVSV provide average tumourdoses that match the MCS results. MVSV is more versatile than OLINDA and can be used to calculate dose distributions that closely resemble the MCSdose for tumours located in regions with reasonably uniform tissue density.