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- Silins, Isabella, 1983-, et al.
(författare)
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First-in-human evaluation of [18F]CETO : a novel tracer for adrenocortical tumours
- 2023
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Nature. - 1619-7070 .- 1619-7089. ; 50:2, s. 398-409
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Tidskriftsartikel (refereegranskat)abstract
- Purpose[11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.MethodsFifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.ResultsUptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65–70, and SUV120 were 25, 22, and 17%.ConclusionsHigh adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki.Trial registrationClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083
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| 2. |
- Silins, Isabella, 1983-, et al.
(författare)
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Radiation dosimetry of para-chloro-2-[18F]fluoroethyl-etomidate:a PET tracer for adrenocortical imaging
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction[11C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer’s rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[18F]fluoroethyl-etomidate, [18F]CETO, a fluorine-18 (T1/2=109.8 min) analogue, as a potential new adrenocortical PET tracer.ObjectivesThe aim of this study was to assess in vivo and in-human radiation dosimetry of [18F]CETO.Methods: Residence times were calculated based on uptake data from rats (n=30, biodistribution study with ex vivo measurements) as well as in vivo PET/CT in cynomolgus (n=1) and humans (n=9). OLINDA 1.1 was used to obtain absorbed doses in human organs (mGy/MBq) and effective dose (mSv/MBq).Results[18F]CETO showed a high uptake in human adrenal glands, still increasing at 90 minutes post injection. Regardless of species used for input data (rat, cynomolgus or human), adrenal glands (absorbed dose 0.093 ± 0.038 mGy/MBq based on human data) were confirmed as the dose-limiting organs. The effective dose based on human data was 18.2 μSv/MBq and varied little when using rat (18.4 μSv/MBq) or cynomolgus data (16.1 μSv/MBq). Conclusions[18F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET/CT examination with 200 MBq [18F]CETO is 3.6 mSv.
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| 3. |
- Ilan, Ezgi, et al.
(författare)
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Comparison of 68Ga-DOTATATE and 177Lu-DOTATATE kinetics in neuroendocrine tumors
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Tidskriftsartikel (refereegranskat)abstract
- Absorbed dose planning prior peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE would allow maximization of the absorbed dose to tumor tissue whilst minimizing the risk for side-effects in healthy organs. Unfortunately, dosimetry during 177Lu-DOTATATE is only possible post therapy and using 68Ga-DOTATATE to act as surrogate for 177Lu-DOTATATE could potentially enable prediction of absorbed doses prior PRRT with 177Lu-DOTATATE. The aim of this study was to compare uptake and kinetics of 68Ga-DOTATATE and 177Lu-DOTATATE in tumors by performing dynamic or serial scans with both radiopharmaceuticals in the same patients. Methods Six NET patients underwent a 45-min dynamic PET scan after injection of 124 ±38 MBq 68Ga-DOTATATE and serial SPECT scans after a bolus injection of 500 ± 0 MBq 177Lu-DOTATATE assuring similar peptide content in the radiopharmaceuticals. Tumor and whole-blood SUV, tumor-to-blood-ratio (TBR), and net influx rate (Ki) were determined for 68Ga-DOTATATE and 177Lu-DOTATATE. Ki was determined by non-linear regression of an irreversible two-tissue compartment model with a loss parameter and by the Patlak method. Results In majority of tumors, tumor SUV was higher in 68Ga-DOTATATE than in 177Lu-DOTATATE and whole-blood SUV was lower in 68Ga-DOTATATE than in 177Lu-DOTATATE, resulting in a lower TBR for 68Ga-DOTATATE than for 177Lu-DOTATATE. For Ki, Spearman correlation was 0.55 between 68Ga- DOTATATE and 177Lu-DOTATATE with a Demining regression slope of 0.93. For Patlak based Ki (with correction for partial volume effect based on data <100 min p.i. for 177Lu-DOTATATE), the Spearman correlation was 0.90 and with a Deming regression slope close to 1 (0.83). Using a later time interval (with correction for partial volume effect based on data >100 min p.i) for the Patlak analysis also resulted in high correlation (0.87) but the Deming regression slope was 0.18. Conclusion Linear relation with good agreement was found between the SUVs of 68Ga-DOTATATE and 177Lu-DOTATATE. Similar Ki was observed for 68Ga-DOTATATE and 177Lu-DOTATATE during early time interval (<100 min p.i of 177Lu-DOTATATE) however not during late time interval (>100 min p.i.). Hence, late kinetics of 177Lu-DOTATATE cannot be predicted using 68Ga-DOTATATE PET.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Jahn, Ulrika, et al.
(författare)
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177Lu-DOTATATE peptide receptor radionuclide therapy : dose response in small intestinal neuroendocrine tumors
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:7-8, s. 662-670
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Peptide receptor radionuclide therapy (PRRT) has during the last few years been frequently used in patients with progressive, disseminating, well-differentiated neuroendocrine tumors (NETs).Objective: To study whether the absorbed dose in small intestinal NET (SI-NET) metastases from PRRT with 177Lu-DOTATATE is related to tumor shrinkage.Materials and Methods: Dosimetry for 1 tumor was performed in each of 25 SI-NET patients based on sequential SPECT/CT 1, 4, and 7 days after 177Lu-DOTATATE infusion. The SPECT data were corrected for the partial volume effect based on previous phantom measurements, and the unit density sphere model from OLINDA was used for absorbed dose calculations. Morphological therapy response was assessed by CT/MRI regarding tumor diameter, tumor volume, total liver tumor volume, liver volume, and overall tumor response according to RECIST 1.1. Plasma chromogranin A and urinary 5-hydroxy-indole-acetic-acid were measured during PRRT and follow-up to assess biochemical response.Results: At the time of best response with respect to tumor diameter and volume shrinkage, the median absorbed dose was 128.6 Gy (range 28.4–326.9) and 140 Gy (range 50.9–487.4), respectively. All metrics regarding tumor shrinkage and biochemical response were unrelated to the absorbed dose. A correlation was, however, found between the administered radioactivity and the tumor volume shrinkage (p = 0.01) and between the administered radioactivity and RECIST 1.1 response (p = 0.01).Conclusions: It was not possible to demonstrate a tumor dose-response relationship in SI-NET metastases with the applied dosimetry method, contrary to what was previously shown for pancreatic NETs.
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| 10. |
- Jahn, Ulrika, et al.
(författare)
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Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression
- 2023
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Ingår i: EJNMMI Research. - : Springer Nature. - 2191-219X. ; 13:1, s. 45-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe accumulation of 177Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients’ tumor load.MethodPatients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation. All patients had received 7.4 GBq 177Lu-DOTATATE, and the amount of administered peptide in the preparation varied from 93 to 456 µg. The absorbed dose in tumors and normal tissue at the first PRRT cycle was calculated, based on SPECT-measurements at day 1, 4, and 7 post-infusion. The total tumor somatostatin receptor expression (tTSSTRE) was calculated on SPECT after 24 h by multiplying the functional tumor volume, delineated by 42% cut-off VOIs of the highest activity, with the SUVmean for the respective tumor VOIs. Spearman’s rank correlation analyzed any relationship between the administered amount of peptide and the absorbed dose in tumors and normal organs, in relation to the patients’ tTSSTRE.ResultsThere was no correlation between the amount of peptide and any of the tested parameters in relation to tTSSTRE.ConclusionIn this retrospective analysis, no correlation between the amount of administered peptide in the 177Lu-DOTATATE preparation and the absorbed radiation doses in tumors and normal tissues was demonstrated in relation to the total tumor SSTR expression.
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