| 51. |
- Harms, Hendrik J., et al.
(författare)
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Noninvasive Quantification of Myocardial C-11-Meta-Hydroxyephedrine Kinetics
- 2016
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 57:9, s. 1376-1381
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Tidskriftsartikel (refereegranskat)abstract
- C-11-meta-hydroxyephedrine (C-11-HED) kinetics in the myocardium can be quantified using a single-tissue-compartment model together with a metabolite-corrected arterial blood sampler input function (BSIF). The need for arterial blood sampling, however, limits clinical applicability. The purpose of this study was to investigate the feasibility of replacing arterial sampling with imaging-derived input function (IDIF) and venous blood samples. Methods: Twenty patients underwent 60-min dynamic C-11-HED PET/CT scans with online arterial blood sampling. Thirteen of these patients also underwent venous blood sampling. Data were reconstructed using both 3 dimensional row-action maximum-likelihood algorithm (3DR) and a time-of-flight (TF) list-mode reconstruction algorithm. For each reconstruction, IDIF results were compared with BSIF results. In addition, IDIF results obtained with venous blood samples and with a transformed venous-to-arterial metabolite correction were compared with results obtained with arterial metabolite corrections. Results: Correlations between IDIF- and BSIF-derived K-1 and V-T were high (r(2) > =0.89 for 3DR and TF). Slopes of the linear fits were significantly different from 1 for K-1, for both 3DR (slope = 0.94) and TF (slope = 1.06). For V-T, the slope of the linear fit was different from 1 for TF (slope = 0.93) but not for 3DR (slope = 0.98). Use of venous blood data introduced a large bias in V-T (r(2) = 0.96, slope = 0.84) and a small bias in K-1 (r(2) = 0.99, slope = 0.98). Use of a second-order polynomial venous-to-arterial transformation was robust and greatly reduced bias in V-T (r(2) = 0.97, slope = 0.99) with no effect on K-1. Conclusion: IDIF yielded precise results for both 3DR and TF. Venous blood samples can be used for absolute quantification of C-11-HED studies, provided a venous-to-arterial transformation is applied. A venous-to-arterial transformation enables noninvasive, absolute quantification of C-11-HED studies.
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| 52. |
- Harms, Hendrik J, et al.
(författare)
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Parametric Images of Myocardial Viability Using a Single 15O-H2O PET/CT Scan
- 2011
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 52:5, s. 745-749
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Tidskriftsartikel (refereegranskat)abstract
- Perfusable tissue index (PTI) is a marker of myocardial viability and requires acquisition of transmission, 15O-CO, and 15O-H2O scans. The aim of this study was to generate parametric PTI images from a 15O-H2O PET/CT scan without an additional 15O-CO scan.Methods:Data from 20 patients undergoing both 15O-H2O and 15O-CO scans were used, assessing correlation between PTI based on 15O-CO (PTICO) and on fitted blood volume fractions (PTIVb). In addition, parametric PTIVb images of 10 patients undergoing 15O-H2O PET/CT scans were generated using basis-function methods and compared with PTIVb obtained using nonlinear regression. Simulations were performed to study the effects of noise on PTIVb.Results:Correlation between PTICO and PTIVb was high (r2 = 0.73). Parametric PTIVb correlated well with PTIVb obtained using nonlinear regression (r2 = 0.91). Simulations showed low sensitivity to noise (coefficient of variation < 10% at 20% noise).Conclusion:Parametric PTI images can be generated from a single 15O-H2O PET/CT scan.
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| 53. |
- Harms, Hendrik J, et al.
(författare)
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Use of a Single 11C-Meta-Hydroxyephedrine Scan for Assessing Flow-Innervation Mismatches in Patients with Ischemic Cardiomyopathy
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:11, s. 1706-1711
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Mismatch between areas of reduced myocardial blood flow (MBF) and reduced myocardial innervation (defect areas) may be used to estimate the risk for ventricular arrhythmias. The presence of a mismatch zone can be derived using a combined protocol consisting of both an MBF scan and an (11)C-meta-hydroxyephedrine ((11)C-HED) scan. The rate of influx from blood to myocardium (K1) of (11)C-HED is proportional to MBF and can potentially be used as an index for defining MBF defects. The aim of this study was to assess whether K1 derived from an (11)C-HED scan can be used as an index of MBF, potentially allowing for an assessment of MBF-innervation mismatch areas from a single (11)C-HED scan.METHODS: Seventeen patients with known ischemic cardiomyopathy underwent dynamic (15)O-water and (11)C-HED scans. Discrete arterial blood samples were taken during (11)C-HED scans for metabolite correction of the image-derived input function. (11)C-HED influx rate was obtained using a single-tissue-compartment model and compared with transmural MBF (MBFT), defined as MBF as measured with (15)O-water multiplied by perfusable tissue fraction. Defect sizes were obtained from parametric K1 and MBFT images, using 50% of a remote control segment as the cutoff value.RESULTS: There was a significant correlation between MBFT and K1 (y = 0.40x + 0.05 mL·g(-1)·min(-1), r = 0.80, P < 0.001), although K1 was significantly lower than MBFT (slope of the regression line significantly different from 1, P < 0.001). Correlation between MBFT and K1 defect sizes was high (y = 0.89x + 1.38%, r = 0.95, P < 0.001), with no significant difference in mean defect size based on K1 or MBFT (20.9% ± 11.3% and 20.1% ± 10.7% for MBFT and K1, respectively, P = 0.41).CONCLUSION: (11)C-HED influx rate K1 can be used as an alternative to a separate MBF scan for assessing mismatch areas between MBF and myocardial innervation.
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| 54. |
- Heskamp, Sandra, et al.
(författare)
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Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with (18)F-Labeled Affibody Molecule Z(HER2:2395) in a Mouse Model for Ovarian Cancer
- 2012
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:1, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are small (7 kDa) proteins with subnanomolar targeting affinity. Previous SPECT studies in xenografts have shown that the Affibody molecule (111)In-DOTA-Z(HER2:2395) can discriminate between high and low human epidermal growth factor receptor type 2 (HER2)-expressing tumors, indicating that radiolabeled Affibody molecules have potential for patient selection for HER2-targeted therapy. Compared with SPECT, PET with positron-emitting radionuclides, such as (18)F, may improve imaging of HER2 expression because of higher sensitivity and improved quantification of PET. The aim of the present study was to determine whether the (18)F-labeled NOTA-conjugated Affibody molecule Z(HER2:2395) is a suitable agent for imaging of HER2 expression. The tumor-targeting properties of (18)F-labeled Z(HER2:2395) were compared with (111)In- and (68)Ga-labeled Z(HER2:2395) in mice with HER2-expressing SK-OV-3 xenografts. Methods: Z(HER2:2395) was conjugated with NOTA and radiolabeled with (18)F, (68)Ga, and (111)In. Radiolabeling with (18)F was based on the complexation of Al(18)F by NOTA. The 50% inhibitory concentration values for NOTA-Z(HER2:2395) labeled with (19)F, (69)Ga, and (115)In were determined in a competitive cell-binding assay using SK-OV-3 cells. Mice bearing subcutaneous SK-OV-3 xenografts were injected intravenously with radiolabeled NOTA-Z(HER2:2395). One and 4 h after injection, PET/CT or SPECT/CT images were acquired, and the biodistribution was determined by ex vivo measurement. Results: The 50% inhibitory concentration values for (19)F-, (69)Ga-, and (115)In-NOTA-Z(HER2:2395) were 5.0, 6.3, and 5.3 nM, respectively. One hour after injection, tumor uptake was 4.4 +/- 0.8 percentage injected dose per gram (% ID/g), 5.6 +/- 1.6 % ID/g, and 7.1 +/- 1.4 % ID/g for (18)F-, (68)Ga-, and (111)In-NOTA-Z(HER2:2395), respectively, and the respective tumor-to-blood ratios were 7.4 +/- 1.8, 8.0 +/- 1.3, and 4.8 +/- 1.3. Tumor uptake was specific, because uptake could be blocked efficiently by coinjection of an excess of unlabeled Z(HER2:2395). PET/CT and SPECT/CT images clearly visualized HER2-expressing SK-OV-3 xenografts. Conclusion: This study showed that (18)F-NOTA-Z(HER2:2395) is a promising new imaging agent for HER2 expression in tumors. Affibody molecules were successfully labeled with (18)F within 30 min, based on the complexation of Al(18)F by NOTA. Further research is needed to determine whether this technique can be used for patient selection for HER2-targeted therapy.
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| 55. |
- Hoek, Roel, et al.
(författare)
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Determining Hemodynamically Significant Coronary Artery Disease : Patient-Specific Cutoffs in Quantitative Myocardial Blood Flow Using [15O]H2O PET Imaging
- 2024
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 65:7, s. 1113-1121
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Tidskriftsartikel (refereegranskat)abstract
- Currently, cutoffs of quantitative [15O]H2O PET to detect fractional flow reserve (FFR)-defined coronary artery disease (CAD) were derived from a single cohort that included patients without prior CAD. However, prior CAD, sex, and age can influence myocardial blood flow (MBF). Therefore, the present study determined the influence of prior CAD, sex, and age on optimal cutoffs of hyperemic MBF (hMBF) and coronary flow reserve (CFR) and evaluated whether cutoff optimization enhanced diagnostic performance of quantitative [15O]H2O PET against an FFR reference standard. Methods: Patients with chronic coronary symptoms underwent [15O]H2O PET and invasive coronary angiography with FFR. Optimal cutoffs for patients with and without prior CAD and subpopulations based on sex and age were determined. Results: This multicenter study included 560 patients. Optimal cutoffs were similar for patients with (n = 186) and without prior CAD (hMBF, 2.3 vs. 2.3 mL center dot min-1 center dot g-1; CFR, 2.7 vs. 2.6). Females (n = 190) had higher hMBF cutoffs than males (2.8 vs. 2.3 mL center dot min-1 center dot g-1), whereas CFRs were comparable (2.6 vs. 2.7). However, female sex-specific hMBF cutoff implementation decreased diagnostic accuracy as compared with the cutoff of 2.3 mL center dot min-1 center dot g-1 (72% vs. 82%, P , 0.001). Patients aged more than 70 y (n = 79) had lower hMBF (1.7 mL center dot min-1 center dot g-1) and CFR (2.3) cutoffs than did patients aged 50 y or less, 51-60 y, and 61-70 y (hMBF, 2.3-2.4 mL center dot min-1 center dot g-1; CFR, 2.7). Age-specific cutoffs in patients aged more than 70 y yielded comparable accuracy to the previously established cutoffs (hMBF, 72% vs. 76%, P = 0.664; CFR, 80% vs. 75%, P = 0.289). Conclusion: Patients with and without prior CAD had similar [15O]H2O PET cutoffs for detecting FFR-defined significant CAD. Stratifying patients according to sex and age led to different optimal cutoffs; however, these values did not translate into an increased overall accuracy as compared with previously established thresholds for MBF.
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| 56. |
- Hsu, David Fc, et al.
(författare)
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Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System
- 2017
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:9, s. 1511-1518
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Tidskriftsartikel (refereegranskat)abstract
- This article presents system performance studies of the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance and clinical imaging comparisons were made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different reconstruction algorithms. Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized with the NEMA NU-2 2012 standards. Energy and coincidence time resolution were measured. Tests were conducted independently and results were averaged on two Discovery MI scanners installed at Stanford and Uppsala University Hospitals. Back-to-back patient scans were also performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) and the "Q.Clear" reconstruction algorithms, and examined qualitatively. Results: The averaged full-width half max (FWHM) of the radial/tangential/axial spatial resolution reconstructed with FBP at 1, 10, and 20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center of the FOV. Averaged peak noise equivalent count rate is 193.4 kcps at 21.9 kBq/mL with a scatter fraction of 40.6%. The averaged contrast recovery coefficients for the image quality phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the high quality of the Discovery MI system. Comparisons between the Discovery MI and SIGNA systems show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM. Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system.
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| 57. |
- Hsu, David, et al.
(författare)
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Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System
- 2017
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: This article presents studies performed with the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance was characterized according to the NEMA NU-2 2012 standards. Comparisons of performance and clinical images were also made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different image reconstruction algorithms.Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized according to the NEMA NU-2 2012 standards. In addition, energy and coincidence time resolution were measured using a line source at the center of the field-of-view (CFOV). Tests were conducted independently on two Discovery MI scanners installed at Stanford University Hospital and Uppsala University Hospital, and results were averaged between the two systems. In addition, back-to-back patient scans were performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) reconstruction algorithms and the block-sequential regularized expectation maximization (BSREM) "Q.Clear" reconstruction algorithm, and examined qualitatively.Results: The averaged FWHM of the radial, tangential, and axial spatial resolution reconstructed with filtered backprojection (FBP) at 1/10/20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center and 13.4 cps/kBq at 10 cm radial offset from the center. Averaged peak noise equivalent count rate (NECR) is 193.4 kcps at 21.9 kBq/mL with a scatter fraction (SF) of 40.6%. The averaged contrast recovery (CR) coefficients for the image quality (IQ) phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres over 3 separate acquisitions. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the very high quality of the Discovery MI system. Comparisons between the Discovery MI PET/CT and SIGNA PET/MR systems, which contain identical detector architectures but with different detector diameters, show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM.Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system. Research Support: None
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| 58. |
- Höglund, Johanna, et al.
(författare)
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F-18-ML-10, a PET Tracer for Apoptosis : First Human Study
- 2011
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 52:5, s. 720-725
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Tidskriftsartikel (refereegranskat)abstract
- Clinical PET of apoptosis may have substantial value in advancing patient care. We report here the first-in-humans study with F-18-labeled 2-(5-fluoropentyl)-2-methyl malonic acid (F-18-ML-10), a small-molecule PET tracer for apoptosis. Presented are the dosimetry, biodistribution, stability, and safety profiles of this PET tracer in healthy human volunteers. Also reported is tracer binding to targeted apoptotic cells in testicular tissue, where a relative abundance of apoptotic cells is normally observed. Methods: F-18-ML-10 (233 +/- 90 MBq) was intravenously administered to 8 healthy subjects, followed by whole-body PET/CT for 220 min. Serial blood and urine samples were collected for radioactivity measurement, and plasma tracer stability was assessed by high-performance liquid chromatography. Dosimetry calculations were performed using OLINDA/EXM software. Results: F-18-ML-10 manifested high stability in vivo and rapid distribution followed by fast clearance, with an elimination half-life of 1.3 +/- 0.1 and 1.1 +/- 0.2 h from the blood and from all other organs, respectively, and excretion through the urine. Dosimetry showed an average effective whole-body dose of 15.4 +/- 3.7 mu Sv/MBq, with the urinary bladder being the dose-limiting organ. Selective accumulation and retention of the tracer in the testes was observed in all male subjects, a finding also demonstrated in mice using both small-animal PET and histopathology, confirming binding to apoptotic cells. Administration of F-18-ML-10 was safe, without adverse effects. Conclusion: F-18-ML-10 administered to healthy humans demonstrated a favorable dosimetry, biodistribution, stability, and safety profile. Binding to apoptotic sites was also demonstrated. These data support further development of this small-molecule probe for clinical PET of apoptosis.
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| 59. |
- Ilan, Ezgi, et al.
(författare)
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Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE
- 2015
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:2, s. 177-182
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE.METHODS: Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors.RESULTS: Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy.CONCLUSION: The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.
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| 60. |
- Ilan, Ezgi, et al.
(författare)
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Parametric Net Influx Rate Images of 68Ga-DOTATOC and 68Ga-DOTATATE : Quantitative Accuracy and Improved Image Contrast
- 2017
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:5, s. 744-749
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Tidskriftsartikel (refereegranskat)abstract
- (68)Ga-DOTATOC and (68)Ga-DOTATATE are radiolabelled somatostatin analogs used for diagnosis of somatostatin receptor expressing neuroendocrine tumors (NETs) and SUV -measurements are suggested for treatment monitoring. However, changes in net-influx rate (Ki) may better reflect treatment effects than those of the SUV, and accordingly there is a need to compute parametric images showing Ki at the voxel level. The aim of this study was to evaluate parametric methods for computation of parametric Ki images by comparison to volume of interest based methods and to assess image contrast in terms of tumor-to-liver ratio.METHODS: Ten patients with metastatic NETs underwent a 45-min dynamic PET examination followed by whole-body PET/CT at 1 h post injection of (68)Ga-DOTATOC and (68)Ga-DOTATATE on consecutive days. Parametric Ki images were computed using a basis function method (BFM) implementation of the two tissue irreversible compartment model and the Patlak method using a descending aorta image-derived input function, and mean tumor Ki values were determined for 50% isocontour VOIs and compared to Ki values based on non-linear regression (NLR) of the whole-VOI time-activity curve. A subsample of healthy liver was delineated in the whole-body and Ki images and tumor-to-liver ratios were calculated in order to evaluate image contrast. Correlation and agreement between VOI-based and parametric Ki values were assessed using regression and Bland-Altman analysis.RESULTS: Correlation (R2) between NLR-based and parametric image-based (BFM) tumor Ki values was 0.98 (slope 0.81) and 0.97 (slope 0.88) for (68)Ga-DOTATOC and (68)Ga DOTATATE, respectively. For Patlak analysis, correlation between NLR-based and parametric based (Patlak) tumor Ki were 0.95 (slope 0.71) and 0.92 (slope 0.74) for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively. There was no bias between NLR and parametric based Ki-values. Tumor-to-liver contrast was 1.6 and 2.0 times higher in the parametric BFM-Ki images, and 2.3 and 3.0 times in the Patlak images, than in the whole-body images for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively.CONCLUSION: A high correlation and agreement between NLR- and parametric based Ki values was found, showing that parametric net influx rate images are quantitatively accurate. In addition, tumor-to-liver contrast was superior in the parametric Ki images compared to whole-body images both for (68)Ga-DOTATOC and (68)Ga DOTATATE.
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