Dosimetry In Radionuclide Therapy Research Articles

Optimization of the number of post-therapeutic planar imaging time points for the most reliable organ and tumour dosimetry in peptide receptor radionuclide therapy

Optimization of the number of post-therapeutic planar imaging time points for the most reliable organ and tumour dosimetry in peptide receptor radionuclide therapy

Investigation and optimization of PET-guided SPECT reconstructions for improved radionuclide therapy dosimetry estimates.

To investigate and optimize the SPECTRE (Single Photon Emission Computed Theranostic REconstruction) reconstruction approach, using the hybrid kernelised expectation maximization (HKEM) algorithm implemented in the software for tomographic image reconstruction (STIR) software library, and to demonstrate the feasibility of performing algorithm exploration and optimization in 2D. Optimal SPECTRE parameters were investigated for the purpose of improving SPECT-based radionuclide therapy (RNT) dosimetry estimates. Using the NEMA IEC body phantom as the test object, SPECT data were simulated to model an early and late imaging time point following a typical therapeutic dose of 8 GBq of 177Lu. A theranostic 68Ga PET-prior was simulated for the SPECTRE reconstructions. The HKEM algorithm parameter space was investigated for SPECT-unique and PET-SPECT mutual features to characterize optimal SPECTRE parameters for the simulated data. Mean and maximum bias, coefficient of variation (COV %), recovery, SNR and root-mean-square error (RMSE) were used to facilitate comparisons between SPECTRE reconstructions and OSEM reconstructions with resolution modelling (OSEM_RM). 2D reconstructions were compared to those performed in 3D in order to evaluate the utility of accelerated algorithm optimization in 2D. Segmentation accuracy was evaluated using a 42% fixed threshold (FT) on the 3D reconstructed data. SPECTRE parameters that demonstrated improved image quality and quantitative accuracy were determined through investigation of the HKEM algorithm parameter space. OSEM_RM and SPECTRE reconstructions performed in 2D and 3D were qualitatively and quantitatively similar, with SPECTRE showing an average reduction in background COV % by a factor of 2.7 and 3.3 for the 2D case and 3D case respectively. The 42% FT analysis produced an average % volume difference from ground truth of 158% and 26%, for the OSEM_RM and SPECTRE reconstructions, respectively. The SPECTRE reconstruction approach demonstrates significant potential for improved SPECT image quality, leading to more accurate RNT dosimetry estimates when conventional segmentation methods are used. Exploration and optimization of SPECTRE benefited from both fast reconstruction times afforded by first considering the 2D case. This is the first in-depth exploration of the SPECTRE reconstruction approach, and as such, it reveals several insights for reconstructing SPECT data using PET side information.

Averaging of absorbed doses: How matter matters.

Dosimetry in radionuclide therapy often requires the calculation of average absorbed doses within and between spatial regions, for example, for voxel-based dosimetry methods, for paired organs, or across multiple tumors. Formation of such averages can be made in different ways, starting from different definitions. The aim of this study is to formally specify different averaging strategies for absorbed doses, and to compare their results when applied to absorbed dose distributions that are non-uniform within and between regions. For averaging within regions, two definitions of the average absorbed dose are considered: the simple average over the region (the region average) and the average when weighting by the mass density (density-weighted region average). The latter is shown to follow from the definition of mean absorbed dose according to the ICRU, and to be consistent with the MIRD formalism. For averaging between different spatial regions, three definitions follow: the volume-weighted, the mass-weighted, and the unweighted average. With respect to characterizing non-uniformity, the different average definitions lead to the use of dose-volume histograms (DVHs) (region average), dose-mass histograms (DMHs) (density-weighted region average), and unweighted histograms (unweighted average). Average absorbed doses are calculated for three worked examples, starting from the different definitions. The first, schematic, example concerns the calculation of the average absorbed dose between two regions with different volumes or mass densities. The second, stylized, example concerns voxel-based dosimetry, for which the average absorbed-dose rate within a region is calculated. The geometries studied include three 177 Lu-filled voxelized spheres, where the sphere masses are held constant while the material compositions, densities, and volumes are varied. For comparison, the mean absorbed-dose rates obtained using unit-density sphere S-values are also included. The third example concerns SPECT/CT-based tumor dosimetry for five patients undergoing therapy with 177 Lu-PSMA and six patients undergoing therapy with 177 Lu-DOTA-TATE, for which the average absorbed-dose rates across multiple tumors are calculated. For the second and third examples, analyses also include representations by histograms. Example 1 shows that the average absorbed doses, calculated using different definitions, can differ considerably if the masses and absorbed doses for two regions are markedly different. From example 2 it is seen that the density-weighted region average is stable under different activity and density distributions and is also in line with results using S-values. In contrast, the region average varies as function of the activity distribution. In example 3, the absorbed dose rates for individual tumors differ by (1.1±4.3)% and (-0.1±0.4)% with maximum deviations of +34.4% and -1.4% for 177 Lu-PSMA and 177 Lu-DOTA-TATE, respectively, when calculated as region averages or density-weighted region averages, with largest deviations obtained when the density is non-uniform. The average absorbed doses calculated across all tumors are similar when comparing mass-weighted and volume-weighted averages but these differ substantially from unweighted averages. Different strategies for averaging of absorbed doses within and between regions can lead to substantially different absorbed-dose estimates. At reporting of radionuclide therapy dosimetry, it is important to specify the averaging strategy applied.

EANM practice guideline for quantitative SPECT-CT

PurposeQuantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases.MethodsThese practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT. The guidelines have also been reviewed and approved by all EANM committees and have been endorsed by the European Association of Nuclear Medicine.ConclusionThe present practice guidelines will help practitioners, scientists and researchers perform high-quality quantitative SPECT-CT and will provide a framework for the continuing development of quantitative SPECT-CT as an established modality.

Initial Testing of an Approximated, Fast Calculation Procedure for Personalized Dosimetry in Radionuclide Therapy Based on Planar Whole-Body Scan and Monte-Carlo Specific Dose Rates from the OpenDose Project.

Individualized dosimetry in nuclear medicine is currently at least advisable in order to obtain the best risk–benefit balance in terms of the maximal dose to lesions and under-threshold doses to radiosensitive organs. This article aims to propose a procedure for fast dosimetric calculations based on planar whole-body scintigraphy (WBS) images and developed to be employed in everyday clinical practice. Methods: For simplicity and legacy reasons, the method is based on planar imaging dosimetry, complemented with some assumptions on the radiopharmaceutical kinetics empirically derived from single-photon emission tomography/computed tomography (SPECT/CT) image analysis. The idea is to exploit a rough estimate of the time-integrated activity as has been suggested for SPECT/CT dosimetry but using planar images. The resulting further reduction in dose estimation accuracy is moderated by the use of a high-precision Monte-Carlo S-factor, such as those available within the OpenDose project. Results: We moved the problem of individualized dosimetry to a transformed space where comparing doses was imparted to the ICRP Average Male/Female computational phantom, resulting from an activity distribution related to patient’s pharmaceutical uptake. This is a fast method for the personalized dosimetric evaluation of radionuclide therapy, bearing in mind that the resulting doses are meaningful in comparison with thresholds calculated in the same framework. Conclusion: The simplified scheme proposed here can help the community, or even the single physician, establish a quantitative guide-for-the-eye approach to individualized dosimetry.

Lesion Quantification Accuracy of Digital 90Y PET Imaging in the Context of Dosimetry in Systemic Fibroblast Activation Protein Inhibitor Radionuclide Therapy.

Therapy with 90Y-labeled fibroblast activation protein inhibitors (90Y-FAPIs) was recently introduced as a novel treatment concept for patients with solid tumors. Lesion and organ-at-risk dosimetry is part of assessing treatment efficacy and safety and requires reliable quantification of tissue uptake. As 90Y quantification is limited by the low internal positron-electron pair conversion rate, the increased effective sensitivity of digital silicon photomultiplier-based PET/CT systems might increase quantification accuracy and, consequently, allow for dosimetry in 90Y-FAPI therapy. The aim of this study was to explore the conditions for reliable lesion image quantification in 90Y-FAPI radionuclide therapy using a digital PET/CT system. Methods: Two tumor phantoms were filled with 90Y solution using different sphere activity concentrations and a constant signal-to-background ratio of 40. The minimum detectable activity concentration was determined, and its dependence on acquisition time (15 vs. 30 min per bed position) and smoothing levels (all-pass vs. 5-mm gaussian filter) was investigated. Quantification accuracy was evaluated at various activity concentrations to estimate the minimum quantifiable activity concentration using contour-based and oversized volume-of-interest-based quantification approaches. A ±20% deviation range between image-derived and true activity concentrations was regarded as acceptable. Tumor dosimetry for 3 patients treated with 90Y-FAPI is presented to project the phantom results to clinical scenarios. Results: For a lesion size of 40 mm and a clinical acquisition time of 15 min, both minimum detectable and minimum quantifiable activity concentrations were 0.12 MBq/mL. For lesion sizes of greater than or equal to 30 mm, accurate quantification was feasible for detectable lesions. Only for the smallest 10-mm sphere, the minimum detectable and minimum quantifiable activity concentrations differ substantially (0.43 vs. 1.97 MBq/mL). No notable differences between the 2 quantification approaches were observed. For the investigated tumors, absorbed dose estimates with reliable accuracy were achievable. Conclusion: For lesion sizes and activity concentrations that are expected to be observed in patients treated with 90Y-FAPI, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate the efficacy and safety of 90Y-FAPI therapy.

The effects of mismatch between SPECT and CT images on quantitative activity estimation – A simulation study

BackgroundQuantitative activity estimation is essential in nuclear medicine imaging. Mismatch between SPECT and CT images at the same imaging time point due to patient movement degrades accuracy in both diagnostic studies and target radionuclide therapy dosimetry. This work aims to study the mismatch effects between CT and SPECT data on attenuation correction (AC), volume-of-interest (VOI) delineation, and registration for activity estimation. MethodsNine 4D XCAT phantoms were generated at 1, 24, and 144 h post In-111 Zevalin injection, varying in activity distributions, body sizes, and organ sizes. Realistic noisy SPECT projections were generated by an analytical projector and reconstructed with a quantitative OS-EM method. CT images were shifted, corresponding to SPECT images at each imaging time point, from -5 to 5 voxels and also according to a clinical reference. The effect of mismatched AC maps was evaluated using mismatched CT images for AC in SPECT reconstruction while VOIs were mapped out from matched CTs. The effect of mismatched VOI drawings was evaluated using mismatched CTs to map out target organs while using matched CTs for AC. The effect of mismatched CT images for registration was evaluated by registering sequential mismatched CTs to align corresponding SPECT images, with no AC and VOI mismatch. Bi-exponential curve fitting was performed to obtain time-integrated activity (TIA). Organ activity errors (%OAE) and TIA errors (%TIAE) were calculated. ResultsAccording to the clinical reference, %OAE was larger for organs near ribs for AC effect. For VOI effect, %OAE was larger for small and low uptake organs. For registration effect, %TIAE were larger when mismatch existed in more numbers of SPECT/CT images, while no substantial difference was observed when using mismatched CT at different imaging time points as registration reference. %TIAE was highest for VOI, followed by registration and AC, e.g., 20.62%±8.61%, 9.33%±4.66% and 1.13%±0.90% respectively for kidneys. ConclusionsThe mismatch between CT and SPECT images poses a significant impact on the accuracy of quantitative activity estimation, attributed particularly from VOI delineation errors. It is recommended to perform registration between emission and transmission images at the same time point to ensure diagnostic and dosimetric accuracy.

Dosimetry in radionuclide therapy: the clinical role of measuring radiation dose.

Radionuclide therapy is a rapidly expanding oncological treatment method. Overwhelmingly, the application of radionuclide therapy in clinical practice relies on fixed or empirical dosing strategies. In principle, the application of dosimetry promises to improve patient outcomes by tailoring administered radionuclide therapy activities to each patient's unique tumour burden and tumour uptake. However, robust prospective data are scarce due to few prospective randomised clinical trials investigating the use of dosimetry in radionuclide therapy. In this Review, we describe the role of dosimetry as it has been applied historically and in modern clinical practice and its potential future applications. We further emphasise areas of future growth and a potential pathway to optimised personalised activity modulation of radionuclide therapy.

Theoretical aspects on the use of single-time-point dosimetry for radionuclide therapy

Objective. This study considers the error distributions for time-integrated activity (TIA) of single-time-point (STP) methods for patient-specific dosimetry in radionuclide therapy. Approach. The general case with the same pharmaceutical labelled with different radionuclides for imaging and therapy are considered for a mono-exponential time-activity curve. Two methods for STP dosimetry, both based on the combination of one activity estimate with the population-mean effective decay constant, are investigated. The cumulative distribution functions (CDFs) and the probability density functions for the two methods are analytically derived for arbitrary distributions of the biological decay constant. The CDFs are used for determining 95% coverage intervals of the relative errors for different combinations of imaging time points, physical decay constants, and relative standard deviations of the biological decay constant. Two examples, in the form of kidney dosimetry in [177Lu]Lu-DOTA-TATE therapy and tumour dosimetry for Na[131I]I therapy for thyroid cancer with dosimetry based on imaging of Na[124I]I, are also studied in more detail with analysis of the sensitivity with respect to errors in the mean biological decay constant and to higher moments of the distribution. Main results. The distributions of the relative errors are negatively skewed, potentially leading to the situation that some TIA estimates are highly underestimated even if the majority of estimates are close to the true value. Significance. The main limitation of the studied STP dosimetry methods is the risk of large underestimations of the TIA.

Does Single Computed Tomography Attenuation Correction able to Surrogate Serial Computed Tomography Attenuation Correction in Single-Photon Emission Computed Therapy Imaging for Peptide Receptor Radionuclide Therapy Dosimetry Result?

Peptide Receptor Radionuclide Therapy (PRRT) is the administration of a radionuclide, such as the Lu-177 label, along with a pharmaceutical agent to destroy the lesion cell. The first cycle of Lu-177 DOTA-TATE is an excellent way to estimate radionuclide uptake for organs at risk. To estimate the absorbed dose for a kidney, serial SPECT-CT imaging with up to five sets is required. In general, serial CT on patients would result in additional external exposure and extra time consuming, especially for low dose CT such as cone beam CT technology. However, by introducing a new method, such as optimized single CT (24 h) to perform with serial SPECT attenuation correction, additional external exposure from serial CT exposure could be reduced.Aims:The purpose of this study is to assess the agreement between single CT scanning as CT attenuation Correction with serial CT scanning for serial SPECT imaging as well as estimated absorbed dose to the organ at risk.Settings and Design:During the first cycle of Lu177-DOTA-TATE, all patients should undergo internal dosimetry technique using SPECT-CT imaging with a PHILIP Brightview XCT gamma camera. The quantifications of SPECT images are being used to measure the uptake activity to the organ. In this investigation, Partik's categorical grading criteria are being used to convert the numeric value of Lin's concordance coefficient into an ordinal scale.Method:Total of 9 patients at our institution was administered with Lu177-DOTA-TATE enroll in this study. SPECT-CT data were acquired using automatic body contouring with a total of 48 angular views at steps of 6° (15 s/projections). The pixel size is 4.66 x 4.66 x 4.66 mm, the images size set to one, and SPECT data has been acquired for three-bed positions extending from the abdomen to the thorax region. Low-dose CT imaging performed at an X-ray tube voltage of 120 kVp.Results:Our current result demonstrated by single CT scanning for SPECT attenuation shown the excellent agreement with standard serial CT imaging for organs at risk such as kidney 0.999, spleen 0.9951, liver 0.9951 and bladder 0.9972.Conclusions:When compared to the previous method, patients benefit significantly more from this study, such as lower CT exposure.

DblurDoseNet: A deep residual learning network for voxel radionuclide dosimetry compensating for single-photon emission computerized tomography imaging resolution.

Current methods for patient-specific voxel-level dosimetry in radionuclide therapy suffer from a trade-off between accuracy and computational efficiency. Monte Carlo (MC) radiation transport algorithms are considered the gold standard for voxel-level dosimetry but can be computationally expensive, whereas faster dose voxel kernel (DVK) convolution can be suboptimal in the presence of tissue heterogeneities. Furthermore, the accuracies of both these methods are limited by the spatial resolution of the reconstructed emission image. To overcome these limitations, this paper considers a single deep convolutional neural network (CNN) with residual learning (named DblurDoseNet) that learns to produce dose-rate maps while compensating for the limited resolution of SPECT images. We trained our CNN using MC-generated dose-rate maps that directly corresponded to the true activity maps in virtual patient phantoms. Residual learning was applied such that our CNN learned only the difference between the true dose-rate map and DVK dose-rate map with density scaling. Our CNN consists of a 3D depth feature extractor followed by a 2D U-Net, where the input was 11 slices (3.3cm) of a given Lu-177 SPECT/CT image and density map, and the output was the dose-rate map corresponding to the center slice. The CNN was trained with nine virtual patient phantoms and tested on five different phantoms plus 42 SPECT/CT scans of patients who underwent Lu-177 DOTATATE therapy. When testing on virtual patient phantoms, the lesion/organ mean dose-rate error and the normalized root mean square error (NRMSE) relative to the ground truth of the CNN method was consistently lower than DVK and MC, when applied to SPECT images. Compared to DVK/MC, the average improvement for the CNN in mean dose-rate error was 55%/53% and 66%/56%; and in NRMSE was 18%/17% and 10%/11% for lesion and kidney regions, respectively. Line profiles and dose-volume histograms demonstrated compensation for SPECT resolution effects in the CNN-generated dose-rate maps. The ensemble noise standard deviation, determined from multiple Poisson realizations, was improved by 21%/27% compared to DVK/MC. In patients, potential improvements from CNN dose-rate maps compared to DVK/MC were illustrated qualitatively, due to the absence of ground truth. The trained residual CNN took about 30 s on a single GPU (Tesla V100) to generate a 512 512 130 dose-rate map for a patient. The proposed residual CNN, trained using phantoms generated from patient images, has potential for real-time patient-specific dosimetry in clinical treatment planning due to its demonstrated improvement in accuracy, resolution, noise, and speed over the DVK/MC approaches.

Renal and Red Marrow Dosimetry in Peptide Receptor Radionuclide Therapy: 20 Years of History and Ahead

The development of dosimetry and studies in peptide receptor radionuclide therapy (PRRT) over the past two decades are reviewed. Differences in kidney and bone marrow toxicity reported between 90Y, 177Lu and external beam radiotherapy (EBRT) are discussed with regard to the physical properties of these beta emitter radionuclides. The impact of these properties on the response to small and large tumors is also considered. Capacities of the imaging modalities to assess the dosimetry to target tissues are evaluated. Studies published in the past two years that confirm a red marrow uptake in 177Lu-DOTATATE therapy, as already observed 20 years ago in 86Y-DOTATOC PET studies, are analyzed in light of the recent developments in the transferrin transport mechanism. The review enlightens the importance (i) of using state-of-the-art imaging modalities, (ii) of individualizing the activity to be injected with regard to the huge tissue uptake variability observed between patients, (iii) of challenging the currently used but inappropriate blood-based red marrow dosimetry and (iv) of considering individual tandem therapy. Last, a smart individually optimized tandem therapy taking benefit of the bi-orthogonal toxicity-response pattern of 177Lu-DOTATATE and of 90Y-DOTATOC is proposed.

Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177Lu-FAP-2286: First-in-Humans Results.

Fibroblast activation protein (FAP) is a promising target for diagnosis and therapy of numerous malignant tumors. FAP-2286 is the conjugate of a FAP-binding peptide, which can be labeled with radionuclides for theranostic applications. We present the first-in-humans results using 177Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177Lu-FAP-2286 was performed on 11 patients with advanced adenocarcinomas of the pancreas, breast, rectum, or ovary after prior confirmation of uptake on 68Ga-FAP-2286 or 68Ga-FAPI-04 PET/CT. Results: Administration of 177Lu-FAP-2286 (5.8 ± 2.0 GBq; range, 2.4-9.9 GBq) was well tolerated, with no adverse symptoms or clinically detectable pharmacologic effects being noticed or reported in any of the patients. The whole-body effective dose was 0.07 ± 0.02 Gy/GBq (range, 0.04-0.1 Gy/GBq). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range, 0.4-2.0 Gy/GBq) and 0.05 ± 0.02 Gy/GBq (range, 0.03-0.09 Gy/GBq), respectively. Significant uptake and long tumor retention of 177Lu-FAP-2286 resulted in high absorbed tumor doses, such as 3.0 ± 2.7 Gy/GBq (range, 0.5-10.6 Gy/GBq) in bone metastases. No grade 4 adverse events were observed. Grade 3 events occurred in 3 patients-1 with pancytopenia, 1 with leukocytopenia, and 1 with pain flare-up; 3 patients reported a pain response. Conclusion:177Lu-FAP-2286 PTRT, applied in a broad spectrum of cancers, was relatively well tolerated, with acceptable side effects, and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted.

Theranostic SPECT reconstruction for improved resolution: application to radionuclide therapy dosimetry

BackgroundSPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution; however, the images produced are prone to noise amplification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction); using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach.MethodsWe have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68Ga/177Lu IEC phantom study and a clinical example using 64Cu/67Cu.ResultsSPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and amplification of noise.ConclusionThe SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise amplification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting.

Dosimetry after peptide receptor radionuclide therapy: impact of reduced number of post-treatment studies on absorbed dose calculation and on patient management

BackgroundAfter each cycle of [177Lu]-DOTA-TATE peptide receptor radionuclide therapy (PRRT) dosimetry is performed to enable precise calculation of the radiation-absorbed dose to tumors and normal organs. Absorbed doses are routinely calculated from three quantitative single-photon emission computed tomography (SPECT) studies corrected by computed tomography (CT) acquired at t1 = 24 h, t2 = 96 h, and t3 = 168 h after the first cycle of treatment. After following cycles, a single SPECT/CT study is performed. The aim of the present study is to assess the feasibility of a “two time point” quantitative SPECT/CT protocol after the first PRRT cycle and its impact on patient management.Quantitative SPECT/CT data of 25 consecutive patients with metastatic neuroendocrine tumors after PRRT were retrospectively analyzed. Radiation-absorbed doses calculated using the standard protocol with three SPECT/CT studies acquired at (t1, t2, t3) were compared to those obtained from three different “two time point” protocols with SPECT/CT studies performed at (t1, t2), (t1, t3), or (t2, t3).ResultsThe best agreement for the cumulative doses absorbed by the kidneys, bone marrow, liver, spleen, and tumors with the conventional protocol was obtained with the (t1, t3) protocol with mean relative differences of − 1.0% ± 2.4%, 0.4% ± 3.1%, − 0.9% ± 4.0%, − 0.8% ± 1.1%, and − 0.5% ± 2.0%, respectively, and correlation coefficients of r = 0.99 for all.In all patients, there was no difference in the management decision of whether or not to stop PRRT because of unsafe absorbed dose to risk organs using either the standard protocol or the (t1, t3) protocol.ConclusionThese preliminary results demonstrate that dosimetry calculations using two quantitative SPECT/CT studies acquired at 24 and 168 h after the first PRRT cycle are feasible and are in good agreement with the standard imaging protocol with no change in patient management decisions, while enabling improved patient comfort and reduced scanner and staff time.

BIGDOSE: software for 3D personalized targeted radionuclide therapy dosimetry.

Advance 3D quantitative radionuclide imaging techniques boost the accuracy of targeted radionuclide therapy (TRT) dosimetry to voxel level. The goal of this work is to develop a comprehensive 3D dosimetric software, BIGDOSE, with new features of image registration and virtual CT for patient-specific dosimetry. BIGDOSE includes a portable graphical user interface written in Python, integrating (I) input of sequential ECT/CT images; (II) segmentation; (III) non-rigid image registration; (IV) curve fitting and voxel-based integration; (V) dose conversion and (VI) 3D dose analysis. The accuracy of the software was evaluated using a simulation study with 9 XCAT phantoms. We simulated SPECT/CT acquisitions at 1, 12, 24, 72 and 144-hrs post In-111 Zevalin injection with inter-scans misalignments using an analytical projector for medium energy general purpose (MEGP) collimator, modeling attenuation, scatter and collimator-detector response. The SPECT data were reconstructed using quantitative OS-EM method. A CT organ-based registration was performed before the dose calculation. Organ absorbed doses for the corresponding Y-90 therapeutic agent were calculated on target organs and compared with those obtained from OLINDA/EXM, using dose measured from GATE as the gold standard. One patient with In-111 DTPAOC injection as well as two patients with Y-90 microsphere embolization were used to demonstrate the clinical effectiveness of our software. In the simulation, the organ dose errors of BIGDOSE were -9.59%±9.06%, -8.36±5.82%, -23.41%±6.67%, -6.05%±2.06% for liver, spleen, kidneys and lungs, while they were -25.72%±12.52%, -14.93%±10.91%, -28.63%±12.97% and -45.30%±5.84% for OLINDA/EXM. Cumulative dose volume histograms, dose maps and iso-dose contours provided 3D dose distribution information on the simulated and patient data. BIGDOSE provides a one-stop platform for voxel-based dose estimation with enhanced functions. It is a promising tool to streamline the current clinical TRT dosimetric practice with high accuracy, incorporating 3D personalized imaging information for improved treatment outcome.

What You See Is Not What You Get: On the Accuracy of Voxel-Based Dosimetry in Molecular Radiotherapy.

Improvements in quantitative SPECT/CT have aroused growing interest in voxel-based dosimetry for radionuclide therapies, because it promises visualization of absorbed doses at a voxel level. In this work, SPECT/CT-based voxel-level dosimetry of a 3-dimensional (3D) printed 2-compartment kidney phantom was performed, and the resulting absorbed dose distributions were examined. Additionally, the potential of the PETPVC partial-volume correction tool was investigated. Methods: Both kidney compartments (70% cortex, 30% medulla) were filled with different activity concentrations, and SPECT/CT imaging was performed. The images were reconstructed using varying settings (iterations, subsets, and postfiltering). On the basis of these activity concentration maps, absorbed dose distributions were calculated with precalculated 177Lu voxel S values and an empiric kidney half-life. An additional set of absorbed doses was calculated after applying PETPVC for partial-volume correction of the SPECT reconstructions. Results: SPECT/CT imaging blurs the 2 discrete suborgan absorbed dose values into a continuous distribution. Although this effect is slightly improved by applying more iterations, it is enhanced by additional postfiltering. By applying PETPVC, the absorbed dose values are separated into 2 peaks. Although this leads to a better agreement between SPECT/CT-based and nominal values, considerable discrepancies remain. In contrast to the calculated nominal absorbed doses of 7.8 and 1.6 Gy (in the cortex and medulla, respectively), SPECT/CT-based voxel-level dosimetry resulted in mean absorbed doses of 3.0-6.6 Gy (cortex) and 2.7-5.1 Gy (medulla). PETPVC led to improved ranges of 6.1-8.9 Gy (cortex) and 2.1-5.4 Gy (medulla). Conclusion: Our study showed that 177Lu quantitative SPECT/CT imaging leads to voxel-based dose distributions largely differing from the real organ distribution. SPECT/CT imaging and reconstruction deficiencies might directly translate into unrealistic absorbed dose distributions, thus questioning the reliability of SPECT-based voxel-level dosimetry. Therefore, SPECT/CT reconstructions should be adapted to ensure an accurate quantification of the underlying activity and, therefore, absorbed dose in a volume of interest of the expected object size (e.g., organs, organ substructures, lesions, or voxels). As an example, PETPVC largely improves the match between SPECT/CT-based and nominal dose distributions. In conclusion, the concept of voxel-based dosimetry should be treated with caution. Specifically, one should remember that the absorbed dose distribution is mainly a convolved version of the underlying SPECT reconstruction.

Quantitative SPECT: a survey of current practice in the UK Nuclear Medicine Community.

Nuclear Medicine is a quantitative imaging modality. However, until recently, quantitative single photon emission computed tomography (SPECT) has been limited to ratios or comparisons to databases, or indeed volume measurements, and therefore has not truly quantified uptake in areas of interest. Following the growth of dosimetry associated with nuclear medicine therapies, tools to perform quantitative SPECT in terms of kBq/cc or standardised uptake value (SUV) have become more readily available, although its use does not appear to be widespread. The aim of this study was to get a snapshot of quantitative SPECT use, and to determine where the future of this technology may lie. The data for this survey were collected through a web-based form made available at a national quantitative SPECT meeting, and later distributed to the UK nuclear medicine community. A series of questions looking at current practice, technique and future thoughts were presented to respondents in the form of multiple-choice questions where single and multiple selections could be made. The responses showed significant use of quantitative SPECT for established techniques, in alignment with the prevalence of the relevant imaging studies. There was a significant minority of respondents performing kBq/cc and SUV SPECT, and SPECT for radionuclide therapy dosimetry. Technique for quantitative SPECT varied significantly typically but nevertheless the predicted future for quantitative SPECT was positive: particularly for kBq/cc and SUV SPECT. Impediments to the success of the technology were mostly around software availability and uncertainties around usefulness. The results of this survey suggest that the future of truly quantitative SPECT looks promising.

Accuracy of kidney dosimetry performed using simplified time activity curve modelling methods: a 177Lu-DOTATATE patient study

177Lu-DOTATATE therapy has been shown to produce encouraging results in treatment of neuroendocrine tumours (NETs). Unfortunately, since dosimetry for radionuclide therapy is considered to be challenging, typically similar amount of radiopharmaceutical is administered to every patient. There is growing evidence that the efficacy of this therapy can be significantly improved by employing personalized protocols, based on the organ-at-risk dosimetry. The aim of this study is to propose a practical and accurate dosimetry protocol based on the simplified acquisition schedules.Data from fifty-three therapy cycles in thirty-nine NET patients were analyzed. Three SPECT/CT scans, acquired at 4 h (D0), 23 h (D1) and 70 h (D3) after injection, were performed. The kidney volume was determined using CT and the activity was determined from quantitative SPECT using an iterative thresholding method. For each dataset, four methods were used to model the time-activity-curves (TAC): M1—two trapezoid segments (0 to D0 and D0 to D1), followed by monoexponential fit to D1 + D3 data; M2—monoexponential fit to D0 + D1 + D3 data; M3 and M4—monoexponential fit to D0 + D3 and D1 + D3 data, respectively. Additionally, kidney doses obtained from single time point method using a monoexponential curve with the population mean effective half-life, normalized to activities at D0 or D1 or D3 points, were calculated. The accuracy of simplified dosimetry methods was assessed as the percentage difference relative to doses calculated from M1.The major contribution to the absorbed dose estimate comes from the area under the late time portion of the TAC (D1 to infinity). Therefore, information from the late scan (D3) is crucial for the determination of kidney absorbed doses. Single time point method using monoexponential TAC, with the population mean effective half-life normalized to the late data point (48–72 h for kidneys) produces <10% deviation in the absorbed dose estimation, thus is recommended for clinical use.

3-D Image-Based Dosimetry in Radionuclide Therapy

Radionuclide therapy is the use of radioactive drugs for internal radiotherapy, mainly for the treatment of metastatic disease. As opposed to systemic cancer therapies in general, the use of radioactively labeled drugs results not only in a targeted therapy but also the possibility of imaging the distribution of the drug during therapy. From such images, the absorbed doses delivered to tumors and organs at risk can be calculated. Calculation of the absorbed dose from 3-D images such as single-photon emission computed tomography (SPECT)/CT, and in some cases positron emission tomography (PET)/CT, relies on image-based activity quantification. Quantification is accomplished by modeling the physics involved in the image-formation process, and applying image-processing methods. From a time-sequence of such quantitative images, the absorbed doses are then calculated. Although individual-patient dosimetry is a standard component of other forms of radiotherapy, it is still overlooked in the majority of radionuclide therapies. In this review, we summarize the physical and technical problems that need to be addressed in image-based dosimetry. The focus is on SPECT, since most of the radionuclides used are single-photon emitters, although the use of PET is also discussed. Practical issues of relevance for the practical implementation of personalized dosimetry in radionuclide therapy are also highlighted.