ABSTRACT
PURPOSE: To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry. MATERIALS AND METHODS: A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland-Altman analysis. RESULTS: A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r2 = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10-12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland-Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively. CONCLUSION: The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose-response relationship, which could ultimately improve future patient outcomes.
ABSTRACT
The purpose of this study is to perform post-administration dosimetry in yttrium-90 radioembolization through micro-CT imaging of radiopaque microsphere distributions in a porcine renal model and explore the impact of spatial resolution of an imaging system on the extraction of specific dose metrics. Following the administration of radiopaque microspheres to the kidney of a hybrid farm pig, the kidney was explanted and imaged with micro-CT. To produce an activity distribution, 400 MBq of yttrium-90 activity was distributed throughout segmented voxels of the embolized vasculature based on an established linear relationship between microsphere concentration and CT voxel value. This distribution was down-sampled to coarser isotropic grids ranging in voxel size from 2.5 to 15 mm to emulate nominal resolutions comparable to those found in yttrium-90 PET and Bremsstrahlung SPECT imaging. Dose distributions were calculated through the convolution of activity distributions with dose-voxel kernels generated using the GATE Monte Carlo toolkit. Contours were computed to represent normal tissue and target volumes. Dose-volume histograms, dose metrics, and dose profiles were compared to a ground truth dose distribution computed with GATE. The mean dose to the target for all studied voxel sizes was found to be within 5.7% of the ground truth mean dose.D70was shown to be strongly correlated with image voxel size of the dose distribution (r2 = 0.90).D70is cited in the literature as an important dose metric and its dependence on voxel size suggests higher resolution dose distributions may provide new perspectives on dose-response relationships in yttrium-90 radioembolization. This study demonstrates that dose distributions with large voxels incorrectly homogenize the dose by attributing escalated doses to normal tissues and reduced doses in high-dose target regions. High-resolution micro-CT imaging of radiopaque microsphere distributions can provide increased confidence in characterizing the absorbed dose heterogeneity in yttrium-90 radioembolization.
Subject(s)
Microspheres , Animals , Kidney/diagnostic imaging , Liver Neoplasms , Swine , X-Ray Microtomography , Yttrium Radioisotopes/therapeutic useABSTRACT
OBJECTIVES: Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as "No Carrier Added" (NCA) 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA-(Tyr3)-octreotate with NCA 177Lu ("NCA-LuTATE") and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB) and quantitative 3D SPECT (qSPECT) 177Lu imaging. METHODS: Thirteen patients received 39 NCA-LuTATE injections. Extensive WB planar and qSPECT imaging was acquired at approximately 0.5, 4, 24 and 96 h to permit estimates of clearance and radiation dose estimation using MIRD-based methodology (OLINDA-EXM). RESULTS: The average amount of NCA-Lutate administered per cycle was 7839±520 MBq. Bi-exponential modelling of whole body clearance showed half lives for the fast & slow components of t½=2.1±0.6 h and t½=58.1±6.6 h respectively. The average effective dose to kidneys was 3.1±1.0 Gy per cycle. In eight patients completing all treatment cycles the average total dose to kidneys was 11.7±3.6 Gy. CONCLUSIONS: We have shown that NCA-LuTATE has an acceptable radiation safety profile and is a suitable alternative to Carrier-Added 177Lu formulations. The fast component of the radiopharmaceutical clearance was closely correlated with baseline renal glomerular filtration rate, and this had an impact on radiation dose to the kidneys. In addition, it has less radioactive waste issues and requires less peptide per treatment.
ABSTRACT
BACKGROUND: Advances in gamma camera technology and the emergence of a number of new theranostic radiopharmaceutical pairings have re-awakened interest in in vivo quantification with single-photon-emitting radionuclides. We have implemented and validated methodology to provide quantitative imaging of (177)Lu for 2D whole-body planar studies and for 3D tomographic imaging with single-photon emission computed tomography (SPECT)/CT. METHODS: Whole-body planar scans were performed on subjects to whom a known amount of [(177)Lu]-DOTA-octreotate had been administered for therapy. The total radioactivity estimated from the images was compared with the known amount of the radionuclide therapy administered. In separate studies, venous blood samples were withdrawn from subjects after administration of [(177)Lu]-DOTA-octreotate while a SPECT acquisition was in progress and the concentration of the radionuclide in the venous blood sample compared with that estimated from large blood pool structures in the SPECT reconstruction. The total radioactivity contained within an internal SPECT calibration standard was also assessed. RESULTS: In the whole-body planar scans (n = 28), the estimated total body radioactivity was accurate to within +4.6 ± 5.9 % (range -17.1 to +11.2 %) of the correct value. In the SPECT reconstructions (n = 12), the radioactivity concentration in the cardiac blood pool was accurate to within -4.0 ± 7.8 % (range -16.1 to +7.5 %) of the true value and the internal standard measurements (n = 89) were within 2.0 ± 8.5 % (range -16.3 to +24.2 %) of the known amount of radioactivity contained. CONCLUSIONS: In our hands, state-of-the-art hybrid SPECT/CT gamma cameras were able to provide accurate estimates of in vivo radioactivity to better than, on average, ±10 % for use in biodistribution and radionuclide dosimetry calculations.
