Simultaneous SPECT imaging with 123I and 125I - a practical approach to assessing a drug and its carrier at the same time with dual imaging.

Radiolabeling of a drug with radioactive iodine is a good method to determine its pharmacokinetics and biodistribution in vivo that only minimally alters its physicochemical properties. With dual labeling, using the two radioactive iodine isotopes 123I and 125I, two different drugs can be evaluated at the same time, or one can follow both a drug and its drug delivery system using a single photon emission computed tomography (SPECT) imager. One difficulty is that the two radioisotopes have overlapping gamma spectra. Our aim was therefore to develop a technique that overcomes this problem and allows for quantitative analysis of the two radioisotopes present at varied isotope ratios. For this purpose, we developed a simple method that included scatter and attenuation corrections and fully compensated for 123I/125I crosstalk, and then tested it in phantom measurements. The method was applied to the study of an orally administered lipid formulation for the delivery of fenofibrate in rats. To directly compare a traditional study, where fenofibrate was determined in plasma samples to SPECT imaging with 123I-labeled fenofibrate and 125I-labeled triolein over 24 h, the drug concentrations were converted to standardized uptake values (SUVs), an unusual unit for pharmaceutical scientists, but the standard unit for radiologists. A generally good agreement between the traditional and the radioactive imaging method was found in the pharmacokinetics and biodistribution results. Small differences are discussed in detail. Overall, SPECT imaging is an excellent method to pilot a new formulation with just a few animals, replaces blood sampling, and can very quickly highlight potential administration problems, the excretion pathways and the kinetics. Furthermore, dual labeling with the two radioisotopes 123I and 125I clearly shows if a drug and its drug delivery system stay together when traveling through the body, if slow drug release takes place, and where degradation/excretion of the components occurs.

Impact of image reconstruction method on dose distributions derived from 90Y PET images: phantom and liver radioembolization patient studies.

PET images acquired after liver 90Y radioembolization therapies are typically very noisy, which significantly challenges both visualization and quantification of activity distributions. To improve their noise characteristics, regularized iterative reconstruction algorithms such as block sequential regularized expectation maximization (Q.Clear for GE Healthcare, USA) have been proposed. In this study, we aimed to investigate the effects which different reconstruction algorithms may have on patient images, with reconstruction parameters initially narrowed down using phantom studies. Moreover, we evaluated the impact of these reconstruction methods on voxel-based dose distribution in phantom and patient studies (lesions and healthy livers). The International Electrotechnical Commission (IEC)/NEMA phantom, containing six spheres, was filled with 90Y and imaged using a GE Discovery 690 PET/CT scanner with time-of-flight enabled. The images were reconstructed using Q.Clear (with ß parameter ranging from 0 to 8000) and ordered subsets expectation maximization. The image quality and quantification accuracy were evaluated by computing the hot ([Formula: see text]) and cold ([Formula: see text]) contrast recovery coefficients, background variability (BV) and activity bias. Next, dose distributions and dose volume histograms were generated using MIM® software's SurePlan LiverY90 toolbox. Subsequently, parameters optimized in these phantom studies were applied to five patient datasets. Dose parameters, such as Dmax, Dmean, D70, and V100Gy, were estimated, and their variability for different reconstruction methods was investigated. Based on phantom studies, the ß parameter values optimized for image quality and quantification accuracy were 2500 and 300, respectively. When all investigated reconstructions were applied to patient studies, Dmean, D50, D70, and V100Gy showed coefficients of variation below 8%; whereas the variability of Dmax was up to 30% for both phantom and patient images. Although ß = 300-1000 would provide accurate activity quantification for a region of interest, when considering activity/dose voxelized distribution, higher ß value (e.g. 4000-5000) would provide the greatest accuracy for dose distributions. In this 90Y radioembolization PET/CT study, the ß parameter in regularized iterative (Q.Clear) reconstruction was investigated for image quality, accurate quantification and dose distributions based on phantom experiments and then applied to patient studies. Our results indicate that more accurate dose distribution can be achieved from smoother PET images, reconstructed with larger ß values than those yielding the best activity quantifications but noisy images. Most importantly, these results suggest that quantitative measures, which are commonly used in clinics, such as SUVmax or SUVpeak( equivalent of Dmax), should not be employed for 90Y PET images, since their values would highly depend on the image reconstruction.

Dual SPECT imaging of 111In and 67Ga to simultaneously determine in vivo the pharmacokinetics of different radiopharmaceuticals: a quantitative tool in pre-clinical research.

Dual-isotope (DI) studies offer a number of advantages in pre-clinical imaging. These include: reducing study times when compared with sequential scans, reducing the number of animals required for any given study, and most importantly, producing images perfectly registered in space and time that provide simultaneous information about two distinct body functions. The ability of single photon emission computed tomography (SPECT) to measure and differentiate energies of the emitted photons makes it well suited for DI imaging. However, since scattered photons originating from one radioisotope may be detected in the energy window of the other and thus degrade image quality and quantitative accuracy, scatter and crosstalk corrections must be applied. The decay characteristics of 111In and 67Ga, which are suitable for quantitative DI imaging for up to 2 weeks post-injection, led us to investigate the performance of simultaneous 111In/67Ga SPECT imaging using a small-animal pre-clinical scanner. A series of phantom experiments were performed to investigate image quality and accuracy of activity quantification in 111In/67Ga images acquired with three different collimators and reconstructed from different photopeak combinations. The triple energy window (TEW) method was used to correct for scatter and crosstalk. Based on these phantom studies, the optimal selection of collimator and energy window settings was determined. When using these optimal settings, submillimeter-size structures were distinguishable in the reconstructed images and quantification errors below 20% were achieved for both isotopes. The optimal parameters were subsequently applied to an in vivo animal study. The determination of the distinct pharmacokinetic profiles of two polymer radiopharmaceuticals injected simultaneously, but by different administration routes (intravenously and intraperitoneally) into a single animal demonstrated the feasibility of simultaneous 111In/67Ga SPECT.

Biodistribution, pharmacokinetics, and organ-level dosimetry for 188Re-AHDD-Lipiodol radioembolization based on quantitative post-treatment SPECT/CT scans.

BACKGROUND: Rhenium-188-labelled-Lipiodol radioembolization is a safe and cost-effective treatment for primary liver cancer. In order to determine correlations between treatment doses and patient response to therapy, accurate patient-specific dosimetry is required. Up to date, the reported dosimetry of 188Re-Lipiodol has been based on whole-body (WB) planar imaging only, which has limited quantitative accuracy. The aim of the present study is to determine the in vivo pharmacokinetics, bio-distribution, and organ-level dosimetry of 188Re-AHDD-Lipiodol radioembolization using a combination of post-treatment planar and quantitative SPECT/CT images. Furthermore, based on the analysis of the pharmacokinetic data, a practical and relatively simple imaging and dosimetry method that could be implemented in clinics for 188Re-AHDD-Lipiodol radioembolization is proposed. Thirteen patients with histologically proven hepatocellular carcinoma underwent 188Re-AHDD-Lipiodol radioembolization. A series of 2-3 WB planar images and one SPECT/CT scan were acquired over 48 h after the treatment. The time-integrated activity coefficients (TIACs, also known as residence-times) and absorbed doses of tumors and organs at risk (OARs) were determined using a hybrid WB/SPECT imaging method. RESULTS: Whole-body imaging showed that 188Re-AHDD-Lipiodol accumulated mostly in the tumor and liver tissue but a non-negligible amount of the pharmaceutical was also observed in the stomach, lungs, salivary glands, spleen, kidneys, and urinary bladder. On average, the measured effective half-life of 188Re-AHDD-Lipiodol was 12.5 ± 1.9 h in tumor. The effective half-life in the liver and lungs (the two organs at risk) was 12.6 ± 1.7 h and 12.0 ± 1.9 h, respectively. The presence of 188Re in other organs was probably due to the chemical separation and subsequent release of the free radionuclide from Lipiodol. The average doses per injected activity in the tumor, liver, and lungs were 23.5 ± 40.8 mGy/MBq, 2.12 ± 1.78 mGy/MBq, and 0.11 ± 0.05 mGy/MBq, respectively. The proposed imaging and dosimetry method, consisting of a single SPECT/CT for activity determination followed by 188Re-AHDD-Lipiodol clearance with the liver effective half-life of 12.6 h, resulted in TIACs estimates (and hence, doses) mostly within ± 20% from the reference TIACs (estimated using three WB images and one SPECT/CT). CONCLUSIONS: The large inter-patient variability of the absorbed doses in tumors and normal tissue in 188Re-HDD-Lipiodol radioembolization patients emphasizes the importance of patient-specific dosimetry calculations based on quantitative post-treatment SPECT/CT imaging.

Determination of gamma camera calibration factors for quantitation of therapeutic radioisotopes.

BACKGROUND: Camera calibration, which translates reconstructed count map into absolute activity map, is a prerequisite procedure for quantitative SPECT imaging. Both planar and tomographic scans using different phantom geometries have been proposed for the determination of the camera calibration factor (CF). However, there is no consensus on which approach is the best. The aim of this study is to evaluate all these calibration methods, compare their performance, and propose a practical and accurate calibration method for SPECT quantitation of therapeutic radioisotopes. Twenty-one phantom experiments (Siemens Symbia SPECT/CT) and 12 Monte Carlo simulations (GATE v6.1) using three therapy isotopes (131I, 177Lu, and 188Re) have been performed. The following phantom geometries were used: (1) planar scans of point source in air (PS), (2) tomographic scans of insert(s) filled with activity placed in non-radioactive water (HS + CB), (3) tomographic scans of hot insert(s) in radioactive water (HS + WB), and (4) tomographic scans of cylinders uniformly filled with activity (HC). Tomographic data were reconstructed using OSEM with CT-based attenuation correction and triple energy window (TEW) scatter correction, and CF was determined using total counts in the reconstructed image, while for planar scans, the photopeak counts, corrected for scatter and background with TEW, were used. Additionally, for simulated data, CF obtained from primary photons only was analyzed. RESULTS: For phantom experiments, CF obtained from PS and HS + WB agreed to within 6% (below 3% if experiments performed on the same day are considered). However, CF from HS + CB exceeded those from PS by 4-12%. Similar trend was found in simulation studies. Analysis of CFs from primary photons helped us to understand this discrepancy. It was due to underestimation of scatter by the TEW method, further enhanced by attenuation correction. This effect becomes less important when the source is distributed over the entire phantom volume (HS + WB and HC). CONCLUSIONS: Camera CF could be determined using planar scans of a point source, provided that the scatter and background contributions are removed, for example using the clinically available TEW method. This approach is simple and yet provides CF with sufficient accuracy (~ 5%) to be used in clinics for radiotracer quantification.

Deadtime effects in quantification of 177Lu activity for radionuclide therapy.

BACKGROUND: The aim of this study was to investigate the deadtime (DT) effects that are present in 177Lu images acquired after radionuclide therapy injection, assess differences in DT based on the full spectrum and the photopeak-only measurements, and design a method to correct for the deadtime losses. A Siemens SymbiaT SPECT/CT camera with a medium energy collimator was used. A 295-mL bottle was placed off-center inside a large cylinder filled with water, and 177Lu activity was sequentially added up to a maximum of 9.12 GBq. The true count rates vs. observed count rates were plotted and fitted to the DT paralyzable model. This analysis was performed using counts recorded in the full spectrum and in other energy windows. The DT correction factors were calculated using the percentage difference between the true and the observed count rates. RESULTS: The DT values of 5.99 ± 0.02 µs, 4.60 ± 0.052 µs, and 0.19 ± 0.18 µs were obtained for the primary photons (PP) recorded in the 113- and 208-keV photopeaks and for the full spectrum, respectively. For the investigated range of count rates, the DT correction factors of up to 23% were observed for PP corresponding to the 113-keV photopeak, while for the 208-keV photopeak values of up to 20% were obtained. These values were almost three times higher than the deadtime correction factors derived from the full spectrum. CONCLUSIONS: The paralyzable model showed to be appropriate for the investigated range of counts, which were five to six times higher than those observed in the patient post-therapy imaging. Our results suggest that the deadtime corrections should be based on count losses in the scatter-corrected photopeak window and not on the deadtime determined from the full spectrum. Finally, a general procedure that can be followed to correct patient images for deadtime is presented.

Accuracy of Rhenium-188 SPECT/CT activity quantification for applications in radionuclide therapy using clinical reconstruction methods.

The main applications of 188Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to perform such dosimetry calculations. However, the accuracy of dosimetry estimates strongly depends on the accuracy of activity quantification in 188Re images. In this study, we performed a series of phantom experiments aiming to investigate the accuracy of activity quantification for 188Re SPECT using high-energy and medium-energy collimators. Objects of different shapes and sizes were scanned in Air, non-radioactive water (Cold-water) and water with activity (Hot-water). The ordered subset expectation maximization algorithm with clinically available corrections (CT-based attenuation, triple-energy window (TEW) scatter and resolution recovery was used). For high activities, the dead-time corrections were applied. The accuracy of activity quantification was evaluated using the ratio of the reconstructed activity in each object to this object's true activity. Each object's activity was determined with three segmentation methods: a 1% fixed threshold (for cold background), a 40% fixed threshold and a CT-based segmentation. Additionally, the activity recovered in the entire phantom, as well as the average activity concentration of the phantom background were compared to their true values. Finally, Monte-Carlo simulations of a commercial [Formula: see text]-camera were performed to investigate the accuracy of the TEW method. Good quantification accuracy (errors <10%) was achieved for the entire phantom, the hot-background activity concentration and for objects in cold background segmented with a 1% threshold. However, the accuracy of activity quantification for objects segmented with 40% threshold or CT-based methods decreased (errors >15%), mostly due to partial-volume effects. The Monte-Carlo simulations confirmed that TEW-scatter correction applied to 188Re, although practical, yields only approximate estimates of the true scatter.

Accuracy of 177Lu activity quantification in SPECT imaging: a phantom study.

BACKGROUND: The aim of the study is to assess accuracy of activity quantification of 177Lu studies performed according to recommendations provided by the committee on Medical Internal Radiation Dose (MIRD) pamphlets 23 and 26. The performances of two scatter correction and three segmentation methods were compared. Additionally, the accuracy of tomographic and planar methods for determination of the camera normalization factor (CNF) was evaluated. Eight phantoms containing inserts of different sizes and shapes placed in air, water, and radioactive background were scanned using a Siemens SymbiaT SPECT/CT camera. Planar and tomographic scans with 177Lu sources were used to measure CNF. Images were reconstructed with our SPEQToR software using resolution recovery, attenuation, and two scatter correction methods (analytical photon distribution interpolated (APDI) and triple energy window (TEW)). Segmentation was performed using a fixed threshold method for both air and cold water scans. For hot water experiments three segmentation methods were compared as folows: a 40% fixed threshold, segmentation based on CT images, and our iterative adaptive dual thresholding (IADT). Quantification error, defined as the percent difference between experimental and true activities, was evaluated. RESULTS: Quantification error for scans in air was better for TEW scatter correction (<6%) than for APDI (<11%). This trend was reversed for scans in water (<10% for APDI and <14% for TEW). For hot water, the best results (<18% for small objects and <5% for objects >100 ml) were obtained when APDI and IADT were used for scatter correction and segmentation, respectively. Additionally, we showed that planar acquisitions with scatter correction and tomographic scans provide similar CNF values. This is an important finding because planar acquisitions are easier to perform than tomographic scans. TEW and APDI resulted in similar quantification errors with APDI showing a small advantage for objects placed in medium with non-uniform density. CONCLUSIONS: Following the MIRD recommendations for data acquisition and reconstruction resulted in accurate activity quantification (errors <5% for large objects). However, techniques for better organ/tumor segmentation must still be developed.

188Re image performance assessment using small animal multi-pinhole SPECT/PET/CT system.

PURPOSE: The goal of this study was to investigate the performance of a pre-clinical SPECT/PET/CT system for 188Re imaging. METHODS: Phantom experiments were performed aiming to assess the characteristics of two multi-pinhole collimators: ultra-high resolution collimator (UHRC) and high-energy ultra high resolution collimator (HE-URHC) for imaging 188Re. The spatial resolution, image contrast and contrast-to-noise ratio (CNR) were investigated using micro-Jaszczak phantoms. Additionally, the quantification accuracy of 188Re images was evaluated using two custom-designed phantoms. The 188Re images were compared to those obtained with 99mTc (gold standard); the acquired energy spectra were analyzed and Monte-Carlo simulations of the UHRC were performed. To verify our findings, a C57BL/6-mouse was injected with 188Re-microspheres and scanned with both collimators. RESULTS: The spatial resolution achieved in 188Re images was comparable to that of 99mTc. Acquisitions using HE-UHRC yielded 188Re images with higher contrast and CNR than UHRC. Studies of quantitative accuracy of 188Re images resulted in <10% errors for both collimators when the activity was calculated within a small VOI around the object of interest. Similar quantification accuracy was achieved for 99mTc. However, 188Re images showed much higher levels of noise in the background. Monte-Carlo simulations showed that 188Re imaging with UHRC is severely affected by down-scattered photons from high-energy emissions. The mouse images showed similar biodistribution of 188Re-microspheres for both collimators. CONCLUSIONS: VECTor/CT provided 188Re images quantitatively accurate and with quality comparable to 99mTc. However, due to large penetration of UHRC by high-energy photons, the use of the HE-UHRC for imaging 188Re in VECTor/CT is recommended.

Accuracy, reproducibility, and uncertainty analysis of thyroid-probe-based activity measurements for determination of dose calibrator settings.

PURPOSE: In the nuclear medicine department, the activity of radiopharmaceuticals is measured using dose calibrators (DCs) prior to patient injection. The DC consists of an ionization chamber that measures current generated by ionizing radiation (emitted from the radiotracer). In order to obtain an activity reading, the current is converted into units of activity by applying an appropriate calibration factor (also referred to as DC dial setting). Accurate determination of DC dial settings is crucial to ensure that patients receive the appropriate dose in diagnostic scans or radionuclide therapies. The goals of this study were (1) to describe a practical method to experimentally determine dose calibrator settings using a thyroid-probe (TP) and (2) to investigate the accuracy, reproducibility, and uncertainties of the method. As an illustration, the TP method was applied to determine 188Re dial settings for two dose calibrator models: Atomlab 100plus and Capintec CRC-55tR. METHODS: Using the TP to determine dose calibrator settings involved three measurements. First, the energy-dependent efficiency of the TP was determined from energy spectra measurements of two calibration sources (152Eu and 22Na). Second, the gamma emissions from the investigated isotope (188Re) were measured using the TP and its activity was determined using γ-ray spectroscopy methods. Ambient background, scatter, and source-geometry corrections were applied during the efficiency and activity determination steps. Third, the TP-based 188Re activity was used to determine the dose calibrator settings following the calibration curve method [B. E. Zimmerman et al., J. Nucl. Med. 40, 1508-1516 (1999)]. The interobserver reproducibility of TP measurements was determined by the coefficient of variation (COV) and uncertainties associated to each step of the measuring process were estimated. The accuracy of activity measurements using the proposed method was evaluated by comparing the TP activity estimates of 99mTc, 188Re, 131I, and 57Co samples to high purity Ge (HPGe) γ-ray spectroscopy measurements. RESULTS: The experimental 188Re dial settings determined with the TP were 76.5 ± 4.8 and 646 ± 43 for Atomlab 100plus and Capintec CRC-55tR, respectively. In the case of Atomlab 100plus, the TP-based dial settings improved the accuracy of 188Re activity measurements (confirmed by HPGe measurements) as compared to manufacturer-recommended settings. For Capintec CRC-55tR, the TP-based settings were in agreement with previous results [B. E. Zimmerman et al., J. Nucl. Med. 40, 1508-1516 (1999)] which demonstrated that manufacturer-recommended settings overestimate 188Re activity by more than 20%. The largest source of uncertainty in the experimentally determined dial settings was due to the application of a geometry correction factor, followed by the uncertainty of the scatter-corrected photopeak counts and the uncertainty of the TP efficiency calibration experiment. When using the most intense photopeak of the sample's emissions, the TP method yielded accurate (within 5% errors) and reproducible (COV = 2%) measurements of sample's activity. The relative uncertainties associated with such measurements ranged from 6% to 8% (expanded uncertainty at 95% confidence interval, k = 2). CONCLUSIONS: Accurate determination/verification of dose calibrator dial settings can be performed using a thyroid-probe in the nuclear medicine department.

Characteristics of Bremsstrahlung emissions of (177)Lu, (188)Re, and (90)Y for SPECT/CT quantification in radionuclide therapy.

PURPOSE: Beta particles emitted by radioisotopes used in targeted radionuclide therapies (TRT) create Bremsstrahlung (BRS) which may affect SPECT quantification when imaging these isotopes. The purpose of the current study was to investigate the characteristics of Bremsstrahlung produced in tissue by three ß-emitting radioisotopes used in TRT. METHODS: Monte Carlo simulations of (177)Lu, (188)Re, and (90)Y sources placed in water filled cylinders were performed. BRS yields, mean energies and energy spectra for (a) all photons generated in the decays, (b) photons that were not absorbed and leave the cylinder, and (c) photons detected by the camera were analyzed. Next, the results of simulations were compared with those from experiments performed on a clinical SPECT camera using same acquisition conditions and phantom configurations as in simulations. RESULTS: Simulations reproduced relatively well the shapes of the measured spectra, except for (90)Y which showed an overestimation in the low energy range. Detailed analysis of the results allowed us to suggest best collimators and imaging conditions for each of the investigated isotopes. Finally, our simulations confirmed that the BRS contribution to the energy spectra in quantitative imaging of (177)Lu and (188)Re could be ignored. CONCLUSIONS: For (177)Lu and (188)Re, BRS contributes only marginally to the total spectra recorded by the camera. Our analysis shows that MELP and HE collimators are the best for imaging these two isotopes. For (90)Y, HE collimator should be used.