| 1. |
- Ilan, Ezgi, et al.
(författare)
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Tumor-to-blood ratio for assessment of somatostatin receptor density in neuroendocrine tumors using 68Ga-DOTATOC and 68Ga-DOTATATE.
- 2020
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 61:2, s. 217-221
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Tidskriftsartikel (refereegranskat)abstract
- PET/CT with 68Ga-DOTA-somatostatin analogs has been tested for therapy monitoring in patients with neuroendocrine tumors (NETs). However, standardized uptake values (SUV) in tumors do not correlate with the net influx rate (Ki), as a representation of the somatostatin receptor (SSTR) expression. In this study, tumor-to-blood-ratio (TBR) was evaluated as an alternative tool for semi-quantitative assessment of 68Ga-DOTATOC and 68Ga-DOTATATE tumor uptake and as a therapy monitoring tool for patients with NETs. Methods: Twenty-two NET patients underwent a 45-min dynamic PET/CT scan after injection of 68Ga-DOTATOC and/or 68Ga-DOTATATE. Ki was determined using the Patlak method and TBR was calculated for the 40-45 min time interval. Results: A linear relation was found between Ki and TBR, with a square of Pearson correlation (R2) of 0.98 and 0.93 for 68Ga-DOTATOC and 68Ga-DOTATATE, respectively. Conclusion: High correlation was found between Ki and TBR. Hence, TBR reflects SSTR density more accurately than SUV and is suggested as the preferred metrics for semi-quantitative assessment of 68Ga-DOTATOC and 68Ga-DOTATATE tumor uptake.
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| 2. |
- Jahn, Ulrika, et al.
(författare)
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Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by Ga-68-DOTATOC PET/CT
- 2021
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-grade neuroendocrine tumors (NETs) are characterized by an abundance of somatostatin receptors (SSTR) that can be targeted with somatostatin analogs (SSA). When activated with a single dose of SSA, the receptor-ligand complex is internalized, and the receptor is by default recycled within 24 h. Ongoing medication with long-acting SSAs at Ga-68-DOTA-SSA-PET has been shown to increase the tumor-to-normal organ contrast. This study was performed to investigate the time-dependent extended effect (7 h) of a single intravenous dose of 400 mu g short-acting octreotide on the tumor versus normal tissue uptake of Ga-68-DOTATOC.Methods: Patients with small-intestinal NETs received a single intravenous dose of 400 mu g octreotide and underwent dynamic abdominal Ga-68-DOTATOC-PET/CT at three sessions (0, 3 and 6 h) plus static whole-body (WB) PET/CT (1, 4 and 7 h), starting each PET/CT session by administering 167 +/- 21 MBq, 23.5 +/- 4.2 mu g (mean +/- SD, n = 12) of Ga-68-DOTATOC. A previously acquired clinical whole-body Ga-68-DOTATOC scan was used as baseline. SUV and net uptake rate K-i were calculated in tumors, and SUV in healthy organs.Results: Tumor SUV decreased significantly from baseline to 1 h post-injection but subsequently increased over time and became similar to baseline at 4 h and 7 h. The tumor net uptake rate, K-i, similarly increased significantly over time and showed a linear correlation both with SUV and tumor-to-blood ratio. By contrast, the uptake in liver, spleen and pancreas remained significantly below baseline levels also at 7 h and the receptor turn-over in tumors thus exceeded that in the normal tissue, with restitution of tumor Ga-68-DOTATOC uptake mainly completed at 7 h. These results however differed depending on tumor size, with significant increases in K-i and SUV between the 1st and 2nd PET, in large tumors (>= 4 mL) but not in small (> 1 to < 4 mL) tumors.Conclusion: SSTR recycling is faster in small-intestinal NETs than in liver, spleen and pancreas. This opens the possibility to protect normal tissues during PRRT by administering a single dose of cold peptide hours before peptide receptor radionuclide therapy (PRRT), and most likely additionally improve the availability and uptake of the therapeutic preparation in the tumors.
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| 3. |
- Jawlakh, Hiba, et al.
(författare)
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Ga-68-DOTATOC-PET/MRI and C-11-5-HTP-PET/MRI are superior to Ga-68-DOTATOC-PET/CT for neuroendocrine tumour imaging
- 2021
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Ingår i: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 33:6
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Tidskriftsartikel (refereegranskat)abstract
- The present study aimed to assess gadoxetate disodium contrast-enhanced (CE) positron emission tomography (PET)/magnetic resonance imaging (MRI) with Ga-68-DOTATOC and C-11-5-Hydroxy-tryptophan (C-11-5-HTP) in comparison with iodine CE Ga-68-DOTATOC-PET/computed tomography (CT) for neuroendocrine tumour imaging. Detection rate and reader's confidence were evaluated for each separate image volume: CE-CT, CE-MRI including diffusion-weighted imaging, Ga-68-DOTATOC-PET performed at PET/CT, Ga-68-DOTATOC-PET performed at PET/MRI and C-11-5-HTP-PET, and for the three combined hybrid examinations Ga-68-DOTATOC-PET/MRI, C-11-5-HTP-PET/MRI and Ga-68-DOTATOC-PET/CT. In 11 patients, 255 lesions were depicted. Ga-68-DOTATOC-PET performed at PET/MRI depicted 72.5%, Ga-68-DOTATOC-PET performed at PET/CT depicted 62.7%, C-11-5-HTP-PET depicted 68.2% and CE-CT depicted 53% of lesions. Ga-68-DOTATOC-PET performed at PET/MRI (P < 0.001) and PET/CT (P = 0.02), C-11-5-HTP-PET (P < 0.001) and MRI (P < 0.001) were superior to CT. Ga-68-DOTATOC-PET/MRI and C-11-5-HTP-PET/MRI detected 92.5% and 92% of lesions, respectively, and both outperformed Ga-68-DOTATOC-PET/CT (65%) (P < 0.001). For liver metastasis imaging, MRI alone was unsurpassed (P < 0.01) and Ga-68-DOTATOC-PET/MRI and C-11-5-HTP-PET/MRI outperformed Ga-68-DOTATOC-PET/CT (P < 0.001). For lymph node metastasis diagnosis, Ga-68-DOTATOC-PET performed at PET/MRI and PET/CT and C-11-5-HTP-PET detected 94%, 94% and 94% of lesions, respectively, and outperformed MRI and CE-CT alone (P < 0.001). For bone metastasis imaging, Ga-68-DOTATOC-PET performed at PET/MRI and PET/CT and C-11-5-HTP-PET performed equally well (P = 0.05) and better than MRI. Reader's confidence was better for Ga-68-DOTATOC-PET/MRI and C-11-5-HTP-PET/MRI than for Ga-68-DOTATOC-PET/CT. The tumour maximum standardised uptake value and tumour-to-liver ratio were both approximately twice as high as for Ga-68-DOTATOC than for C-11-5-HTP. Ga-68-DOTATOC-PET/MRI and C-11-5-HTP-PET/MRI provided the highest detection rates and reader's confidence and were both superior to Ga-68-DOTATOC-PET/CT, mainly because of the MRI component. The imaging contrast with Ga-68-DOTATOC was superior to that of C-11-5-HTP.
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| 4. |
- Lubberink, Mark, et al.
(författare)
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In vivo instability of 177Lu-DOTATATE during peptide receptor radionuclide therapy
- 2020
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 61:9, s. 1337-1340
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Tidskriftsartikel (refereegranskat)abstract
- Peptide receptor radiotherapy using 177Lu-labeled somatostatin ligand analogs is a well-established treatment for neuroendocrine tumors, with 177Lu-DOTATATE having acquired marketing authorization in Europe and the United States. The investigation of the pharmacokinetics of these radiopharmaceuticals in vivo in humans is crucial for personalized treatment management and understanding of treatment effects. Such an investigation requires input data on the in vivo stability of the radiopharmaceuticals in blood and plasma. The work presented here is devoted to the investigation of the in vivo stability of 177Lu-DOTATATE in humans affected by neuroendocrine tumors.Methods: Blood samples of 6 patients undergoing 177Lu-DOTATATE were taken at 0.5, 4, 24, and 96 h after injection. Analysis of metabolic stability was performed using high-performance liquid chromatography.Results: A fast metabolism of the radiopharmaceutical was observed, with the fraction of intact 177Lu-DOTATATE in plasma decreasing rapidly to 23% ± 5% (mean ± SD) at 24 h and 1.7% ±0. 9% at 96 h after injection.Conclusion: The in vivo stability of 177Lu-DOTATATE is much lower than previously assumed, with the major part of radioactivity in plasma consisting of 177Lu-labeled metabolites already at 24 h after injection.
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| 5. |
- Sigfridsson, Jonathan, et al.
(författare)
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Prospective data-driven respiratory gating of [Ga-68]Ga-DOTATOC PET/CT
- 2021
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of this prospective study was to evaluate a data-driven gating software's performance, in terms of identifying the respiratory signal, comparing [Ga-68]Ga-DOTATOC and [F-18]FDG examinations. In addition, for the [Ga-68]Ga-DOTATOC examinations, tracer uptake quantitation and liver lesion detectability were assessed.Methods: Twenty-four patients with confirmed or suspected neuroendocrine tumours underwent whole-body [Ga-68]Ga-DOTATOC PET/CT examinations. Prospective DDG was applied on all bed positions and respiratory motion correction was triggered automatically when the detected respiratory signal exceeded a certain threshold (R value >= 15), at which point the scan time for that bed position was doubled. These bed positions were reconstructed with quiescent period gating (QPG), retaining 50% of the total coincidences. A respiratory signal evaluation regarding the software's efficacy in detecting respiratory motion for [Ga-68]Ga-DOTATOC was conducted and compared to [F-18]FDG data. Measurements of SUVmax, SUVmean, and tumour volume were performed on [Ga-68]Ga-DOTATOC PET and compared between gated and non-gated images.Results: The threshold of R >= 15 was exceeded and gating triggered on mean 2.1 bed positions per examination for [Ga-68]Ga-DOTATOC as compared to 1.4 for [F-18]FDG. In total, 34 tumours were evaluated in a quantitative analysis. An increase of 25.3% and 28.1%, respectively, for SUVmax (P < 0.0001) and SUVmean (P < 0.0001), and decrease of 21.1% in tumour volume (P < 0.0001) was found when DDG was applied.Conclusions: High respiratory signal was exclusively detected in bed positions where respiratory motion was expected, indicating reliable performance of the DDG software on [Ga-68]Ga-DOTATOC PET/CT. DDG yielded significantly higher SUVmax and SUVmean values and smaller tumour volumes, as compared to non-gated images.
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| 6. |
- Strömbeck, Anna, et al.
(författare)
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Fecal microbiota composition is linked to the postoperative disease course in patients with Crohn's disease
- 2020
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Ingår i: BMC Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The role of the fecal microbiota composition for the postoperative disease course of patients with Crohn's disease (CD) who have undergone ileocecal resection remains to be established. In this study, we investigated if the fecal microbiota composition, determined by a high throughput test quantifying a pre-selected set of bacteria, is associated with the postoperative disease course of CD patients. Methods Fecal samples were obtained from healthy subjects as well as from CD patients, 3-10 weeks and 1 year after ileocaecal resection. The fecal microbial composition was analyzed by Genetic Analysis GA-map Dysbiosis test, targeting >= 300 bacteria on different taxonomic levels. Postoperative disease status was assessed endoscopically according to Rutgeerts scoring system 1 year after surgery. Differences in fecal microbiota composition between groups were analyzed by multivariate factor analyses and cluster analysis. Microbial stability over time was determined using Bray-Curtis dissimilarity. Results One year after surgery, the fecal microbiota composition differed between CD patients (n = 21) and healthy subjects (n = 7). At this time point, the microbiota composition of CD patients was associated with disease course, clearly separating patients with disease relapse (n = 8) and patients in remission (n = 13). Further, the microbial within-patient stability was high during the first year after surgery, irrespective of disease course. Conclusion The fecal microbiota composition of CD patients, analyzed by GA-map Dysbiosis test, is subject to little variation over time, and may potentially be used as a non-invasive diagnostic tool for the postoperative disease course.
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