| 1. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy
- 2014
-
Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:48
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Selective arterial radioembolisation of liver tumours has increased, because of encouraging efficacy reports; however, therapeutic parameters used in external beam therapy are not applicable for understanding and predicting potential toxicity and efficacy, necessitating further studies of the physical and biological characteristics of radioembolisation. The aim was to characterise heterogeneity in the distribution of microspheres on a therapeutically relevant geometric scale considering the range of yttrium-90 (90Y) β-particles. METHODS Two patients with intrahepatic cholangiocarcinoma, marginally resectable, were treated by selective arterial embolisation with 90Y resin microspheres (SIRTEX®), followed 9 days post-infusion by resection, including macroscopic tumour tissue and surrounding normal liver parenchyma. Formalin-fixed, sectioned resected tissues were exposed to autoradiographic films, or tissue biopsies of various dimensions were punched out for activity measurements and microscopy. RESULTS Autoradiography and activity measurements revealed a higher activity in tumour tissue compared to normal liver parenchyma. Heterogeneity in activity distribution was evident in both normal liver and tumour tissue. Activity measurements were analysed in relation to the sample mass (5 to 422 mg), and heterogeneities were detected by statistical means; the larger the tissue biopsies, the smaller was the coefficient of variation. The skewness of the activity distributions increased with decreasing biopsy mass. CONCLUSIONS The tissue activity distributions in normal tissue were heterogeneous on a relevant geometric scale considering the range of the ionising electrons. Given the similar and repetitive structure of the liver parenchyma, this finding could partly explain the tolerance of a relatively high mean absorbed dose to the liver parenchyma from β-particles. Keywords: Radioembolisation; Y-90; SIR; Surgery; Activity heterogeneity
|
|
| 2. |
- Högberg, Jonas, 1976, et al.
(författare)
-
Increased absorbed liver dose in Selective Internal Radiation Therapy (SIRT) correlates with increased sphere-cluster frequency and absorbed dose inhomogeneity
- 2015
-
Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 2:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The higher tolerated mean absorbed dose for selective internal radiation therapy (SIRT) with intra-arterially infused 90Y microspheres compared to external beam therapy is speculated to be caused by absorbed dose inhomogeneity, which allows for liver regeneration. However, the complex liver microanatomy and rheology makes modelling less valuable if the tolerance doses are not based on the actual microsphere distribution. The present study demonstrates the sphere distribution and small-scale absorbed dose inhomogeneity and its correlation with the mean absorbed dose in liver tissue resected after SIRT. Methods A patient with marginally resectable cholangiocarcinoma underwent SIRT 9 days prior to resection including adjacent normal liver tissue. The resected specimen was formalin-fixed and sliced into 1 to 2-mm sections. Forty-one normal liver biopsies 6-8 mm in diameter were punched from these sections and the radioactivity measured. Sixteen biopsies were further processed for detailed analyses by consecutive serial sectioning of 15 30-μm sections per biopsy, mounted and stained with haematoxylin-eosin. All sections were scrutinised for isolated or conglomerate spheres. Small-scale dose distributions were obtained by applying a 90Y-dose point kernel to the microsphere distributions. Results A total of 3888 spheres were found in the 240 sections. Clusters were frequently found as strings in the arterioles and as conglomerates in small arteries, with the largest cluster comprising 453 spheres. An increased mean absorbed dose in the punch biopsies correlated with large clusters and a greater coefficient of variation. In simulations the absorbed dose was 5–1240 Gy; 90% were 10-97 Gy and 45% were <30 Gy, the assumed tolerance in external beam therapy. Conclusions Sphere clusters were located in both arterioles and small arteries and increased in size with increasing sphere concentration, resulting in increased absorbed dose inhomogeneity, which contradicts earlier modelling studies.
|
|
| 3. |
- Sundlöv, Anna, et al.
(författare)
-
Individualised Lu-177-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry
- 2017
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 44:9, s. 1480-1489
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose To present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED). Method Treatment was given with repeated cycles of 7.4 GBq 177Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 +/- 2 Gy (alpha/beta = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 +/- 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR). Results Fifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function. Conclusions Individualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned.
|
|
| 4. |
- Sundlöv, Anna, et al.
(författare)
-
Pituitary function after high-dose 177Lu-DOTATATE therapy and long-term follow-up.
- 2021
-
Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:4, s. 344-353
-
Tidskriftsartikel (refereegranskat)abstract
- The pituitary gland has a high expression of somatostatin receptors (SSTRs) and is therefore a potential organ at risk for radiation-induced toxicity after 177Lu-DOTATATE treatment.To study changes in pituitary function in patients with neuroendocrine tumors (NETs) treated with dosimetry-based 177Lu-DOTATATE to detect possible late toxicity.68 patients from a phase II clinical trial of dosimetry-based, individualized 177Lu-DOTATATE-therapy were included in this analysis. Patients had received a median of 5 (range 3-9) treatment cycles of 7.4 GBq/cycle. Median follow-up was 30 months (range 11-89). The GH/IGF1-axis, gonadotropins, adrenal and thyroid axes were analyzed from baseline and on a yearly basis thereafter. Percent changes in hormonal levels over time were analyzed statistically using a linear mixed model and described graphically using boxplots. The absorbed radiation dose to the pituitary was estimated based on post-therapeutic imaging, and the results analyzed vs % change in IGF1-levels over time.A statistically significant decrease in the levels of IGF1 was found (p<0.005), which was correlated to the number of treatment cycles (p=0.008) and absorbed radiation dose (p=0.03). A similar decrease, although non-significant, was seen in the gonadotropins in post-menopausal women, while in men there was an increase during the first years post-therapy, after which the levels returned to baseline. No change was observed in the adrenal nor thyroid axes.No signs of severe endocrine disorder were detected, although a significant decrease in the GH/IGF1-axis was found, where dosimetric analyses indicate radiation-induced damage to the pituitary gland as a probable cause.
|
|
| 5. |
- Benjegård, S A, et al.
(författare)
-
Evaluation of three gamma detectors for intraoperative detection of tumors using 111In-labeled radiopharmaceuticals.
- 1999
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 40:12, s. 2094-101
-
Tidskriftsartikel (refereegranskat)abstract
- Attempts to detect tumors with intraoperative scintillation using tumor-binding radiopharmaceuticals have intensified recently. In some cases previously unknown lesions were found, but in most cases no additional lesions were detected. In this study the physical characteristics of three detector systems and their ability to detect tumors through accumulation of an 111In-labeled radiopharmaceutical were investigated. The first was a sodium iodide (NaI[TI]) detector; the second, a cesium iodide (CsI[TI]) detector; and the third, a cadmium telluride (CdTe) detector.
|
|
| 6. |
- Hagmarker, Linn, et al.
(författare)
-
Bone Marrow Absorbed Doses and Correlations with Hematologic Response During Lu-177-DOTATATE Treatments Are Influenced by Image-Based Dosimetry Method and Presence of Skeletal Metastases
- 2019
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 60:10, s. 1406-1413
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to compare different image-based methods for bone marrow dosimetry and study the dose-response relationship during treatment with Lu-177-DOTATATE in patients with and without skeletal metastases. Methods: This study included 46 patients with advanced neuroendocrine tumors treated with at least 2 fractions of Lu-177-DOTATATE at Sahlgrenska University Hospital. High- and low-uptake compartments were automatically outlined in planar images collected at 2, 24, 48, and 168 h after injection. The bone marrow absorbed doses were calculated from the cross doses of the high- and low-uptake compartments and the self-dose, using the time-activity concentration curve for the low-uptake compartment. This time-activity concentration curve was adjusted using a fixed constant of 1.8 for the planar dosimetry method and using the activity concentrations in vertebral bodies in SPECT images at 24 h after injection of Lu-177-DOTATATE in 4 hybrid methods: L4-SPECT used the activity concentration in the L4 vertebra, whereas V-SPECT, L-SPECT, and T-SPECT used the median activity concentration in all visible vertebrae, lumbar vertebrae, and thoracic vertebrae, respectively. Results: Using the planar method, L4-SPECT, V-SPECT, L-SPECT, and T-SPECT, the estimated median bone marrow absorbed doses were 0.19, 0.36, 0.40, 0.39, and 0.46 Gy/7.4 GBq, respectively, with respective ranges of 0.12-0.33, 0.15-1.44, 0.19-1.71, 0.21-1.60, and 0.18-2.12 Gy/7.4 GBq. For all methods, the bone marrow absorbed dose significantly correlated with decreased platelet counts. This correlation increased after treatment fraction 2: the Spearman correlation (r(s)) were -0.49 for the planar method, -0.61 for L4-SPECT, -0.63 for V-SPECT, -0.63 for L-SPECT, and -0.57 for T-SPECT. A separate analysis revealed an increased correlation for patients without skeletal metastases using the planar method (r(s) = -0.67). In contrast, hybrid methods had poor correlations for patients without metastases and stronger correlations for patients with skeletal metastases (r(s) = -0.61 to -0.74). The mean bone marrow absorbed doses were 3%-69% higher for patients with skeletal metastases than for patients without. Conclusion: The estimated bone marrow absorbed doses by image-based techniques and the correlation with platelets are influenced by the choice of measured vertebrae and the presence of skeletal metastases.
|
|
| 7. |
|
|
| 8. |
- Magnander, Tobias, et al.
(författare)
-
A novel statistical analysis method to improve the detection of hepatic foci of (111)In-octreotide in SPECT/CT imaging.
- 2016
-
Ingår i: EJNMMI physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Low uptake ratios, high noise, poor resolution, and low contrast all combine to make the detection of neuroendocrine liver tumours by (111)In-octreotide single photon emission tomography (SPECT) imaging a challenge. The aim of this study was to develop a segmentation analysis method that could improve the accuracy of hepatic neuroendocrine tumour detection.
|
|
| 9. |
- Svensson, Johanna, et al.
(författare)
-
A novel planar image-based method for bone marrow dosimetry in (177)Lu-DOTATATE treatment correlates with haematological toxicity.
- 2016
-
Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- (177)Lu-DOTATATE is a valuable treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. Though well tolerated in general, bone marrow toxicity can, besides renal exposure, become dose limiting and affect the ability to sustain future therapies. The aim of this study was to develop a novel planar image-based method for bone marrow dosimetry and evaluate its correlation with haematological toxicity during (177)Lu-DOTATATE treatment. In this study, 46 patients with advanced neuroendocrine tumours were treated with 7.2GBq (3.5-8.3GBq) of (177)Lu-DOTATATE on two to five occasions. Planar gamma camera images were acquired at 2, 24, 48 and 168h post-injection. Whole-body regions of interest were created in the images, and a threshold-based segmentation algorithm was applied to separate the uptake of (177)Lu-DOTATATE into high and low uptake compartments. The conjugate view method was used to quantify the activity, the accumulated activity was calculated and the absorbed dose to the bone marrow was estimated according to the MIRD scheme. Patients were monitored for haematological toxicity based on haemoglobin (Hb), white blood cell (WBC) and platelet (PLT) counts every other week during the treatment period.The mean absorbed dose to the bone marrow was estimated to 0.20Gy (0.11-0.37Gy) per 7.4GBq of (177)Lu-DOTATATE, and the mean dose per fraction correlated with a decrease in Hb (p=0.01), WBC (p<0.01) and PLT (p<0.01) counts. The total mean absorbed dose to the bone marrow was 0.64Gy (0.30-1.5Gy) per 24GBq (8.2-37GBq) of (177)Lu-DOTATATE and also correlated with a decrease in Hb (p<0.01), WBC (p=0.01) and PLT (p<0.01) counts.The planar image-based method developed in this study resulted in similar absorbed doses to the bone marrow as reported in earlier studies with blood-based bone marrow dosimetry. The results correlated with haematological toxicity, making it a promising method for estimating bone marrow doses in (177)Lu-DOTATATE treatment without the need for blood and urine sampling.
|
|
| 10. |
- Hagmarker, Linn, et al.
(författare)
-
Segmentation of Whole-Body Images into Two Compartments in Model for Bone Marrow Dosimetry Increases the Correlation with Hematological Response in Lu-177-DOTATATE Treatments
- 2017
-
Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 32:9, s. 335-343
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In Lu-177-DOTATATE treatments, bone marrow (BM) is one of the most important organs at risk. The authors previously developed an image-based two-compartment method for BM dosimetry, showing a significant correlation between absorbed dose to BM and hematological toxicity in Lu-177-DOTATATE treatments. In the present study, they aimed to further evaluate this BM dosimetry method by finding optimal settings for dividing the whole body into two compartments; in terms of minimizing the coefficient of variation (CV) for the individual absorbed doses and studying its correlation to the BM response. The authors have also added specific absorbed fractions for male and female. Finally, they compare this two-compartment method with whole-body dosimetry. Methods: This study included 46 patients with advanced neuroendocrine tumors treated with Lu-177-DOTATATE on two to five occasions at Sahlgrenska University Hospital. Planar gamma camera images were collected at four time points postinjection, and a segmentation tool using a normalized number of uptake foci (nNUF) to divide the whole body into high- and low-uptake compartments was used. The authors characterized the two-compartment model and compared it with whole-body dosimetry. Results and Conclusion: The dosimetry method was robust, with an optimal nNUF value of 0.1-0.2. Using an nNUF value of 0.15, the absorbed BM dose was estimated as 0.20Gy/7.4GBq, and the CV as 8.4%. Compared to whole-body dosimetry, stronger correlation was found between absorbed dose to BM and hematological response using the two-compartment method. The two-compartment method has potential as a valuable image-based alternative to blood-based BM dosimetry.
|
|
