Dosimetric analyses of intra-arterial versus standard intravenous administration of 177Lu-DOTATATE in patients of well differentiated neuroendocrine tumor with liver-dominant metastatic disease

2021 ◽  
pp. 20210403
Author(s):  
Parul Thakral ◽  
Ishita Sen ◽  
Subha Shankar Das ◽  
Divya Manda ◽  
Virupakshappa CB ◽  
...  
Keyword(s):  
Single Dose ◽  
Neuroendocrine Tumor ◽  
Metastatic Disease ◽  
Intravenous Administration ◽  
Radionuclide Therapy ◽  
Organs At Risk ◽  
Hepatic Metastases ◽  
Whole Body ◽  
Intravenous Route ◽  
The Mean

Objective: The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of 177Lu-DOTATATE. Methods: 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of 177Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of 177 Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post 177Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software. Results: The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2–251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12–55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group. Conclusion: IA administration of 177Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT. Advances in knowledge: Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with 177Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.

scholarly journals Kinetic analysis and optimisation of 18F-rhPSMA-7.3 PET imaging of prostate cancer

2021 ◽  
Author(s):  
Simona Malaspina ◽  
Vesa Oikonen ◽  
Anna Kuisma ◽  
Otto Ettala ◽  
Kalle Mattila ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Uptake Kinetics ◽  
Whole Body ◽  
Target Area ◽  
Post Injection ◽  
The Mean ◽  
Pet Radiopharmaceutical ◽  
Time Frames ◽  
Over Time

Abstract Purpose This phase 1 open-label study evaluated the uptake kinetics of a novel theranostic PET radiopharmaceutical, 18F-rhPSMA-7.3, to optimise its use for imaging of prostate cancer. Methods Nine men, three with high-risk localised prostate cancer, three with treatment-naïve hormone-sensitive metastatic disease and three with castration-resistant metastatic disease, underwent dynamic 45-min PET scanning of a target area immediately post-injection of 300 MBq 18F-rhPSMA-7.3, followed by two whole-body PET/CT scans acquired from 60 and 90 min post-injection. Volumes of interest (VoIs) corresponding to prostate cancer lesions and reference tissues were recorded. Standardised uptake values (SUV) and lesion-to-reference ratios were calculated for 3 time frames: 35–45, 60–88 and 90–118 min. Net influx rates (Ki) were calculated using Patlak plots. Results Altogether, 44 lesions from the target area were identified. Optimal visual lesion detection started 60 min post-injection. The 18F-rhPSMA-7.3 signal from prostate cancer lesions increased over time, while reference tissue signals remained stable or decreased. The mean (SD) SUV (g/mL) at the 3 time frames were 8.4 (5.6), 10.1 (7) and 10.6 (7.5), respectively, for prostate lesions, 11.2 (4.3), 13 (4.8) and 14 (5.2) for lymph node metastases, and 4.6 (2.6), 5.7 (3.1) and 6.4 (3.5) for bone metastases. The mean (SD) lesion-to-reference ratio increases from the earliest to the 2 later time frames were 40% (10) and 59% (9), respectively, for the prostate, 65% (27) and 125% (47) for metastatic lymph nodes and 25% (19) and 32% (30) for bone lesions. Patlak plots from lesion VoIs signified almost irreversible uptake kinetics. Ki, SUV and lesion-to-reference ratio estimates showed good agreement. Conclusion 18F-rhPSMA-7.3 uptake in prostate cancer lesions was high. Lesion-to-background ratios increased over time, with optimal visual detection starting from 60 min post-injection. Thus, 18F-rhPSMA-7.3 emerges as a very promising PET radiopharmaceutical for diagnostic imaging of prostate cancer. Trial Registration NCT03995888 (24 June 2019).

scholarly journals Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops

2019 ◽  
pp. 145749691987448 ◽  
Author(s):  
J. Eriksson ◽  
O. Norlén ◽  
M. Ögren ◽  
H. Garmo ◽  
C. Ihre-Lundgren ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Metastatic Disease ◽  
High Rate ◽  
Primary Tumors ◽  
The People ◽  
Swedish Cancer Registry ◽  
The Mean ◽  
Small Intestinal ◽  
Diagnostic Modalities

Background: Small intestinal neuroendocrine tumors are the most common of small bowel malignancies with a clinical incidence of about 1 per 100,000 persons per year. There has been a threefold increase in the incidence of small intestinal neuroendocrine tumor during later decades, but there are no studies that clarify whether this is due to a true higher incidence or if the rise is a mere product of, for instance, improved diagnostic modalities. The aim of this study was to investigate the incidence of clinical as well as subclinical small intestinal neuroendocrine tumors found at autopsy as well as describing the frequency of concomitant malignancies in patients with small intestinal neuroendocrine tumor. Materials and methods: An autopsy registry from the Malmö county population from 1970 to 1982 with an 87% autopsy rate was used. The clinical autopsy reports for patients coded for the existence of “carcinoid tumor” were scrutinized for the presence of small intestinal neuroendocrine tumor, metastatic disease, and concomitant malignancies. Details of patients with clinically diagnosed small intestinal neuroendocrine tumor during this time period were gathered from the Swedish Cancer Registry. Results: The mean annual incidence of small intestinal neuroendocrine tumor during this period was 5.33 per 100,000 individuals, and the mean annual prevalence was 581 per 100,000. The cause of death in the majority of cases was not due to small intestinal neuroendocrine tumor. In total, 48% of the people with small intestinal neuroendocrine tumor had at least one other malignancy, most commonly colorectal cancer. Conclusion: Most small intestinal neuroendocrine tumors are subclinical, and persons living with them will often die due to other causes. There was a high rate of multiple primary tumors (40%), suggesting that multiple tumors seem to arise before the advent of metastatic disease. Moreover, a comparably high rate of associated colorectal carcinoma was found.

scholarly journals Paraganglioma of the thyroid gland: A case report

2014 ◽  
Vol 71 (9) ◽  
pp. 875-878 ◽  
Author(s):  
Aleksandar Filipovic ◽  
Ljiljana Vuckovic ◽  
Ljubica Pejakov
Keyword(s):  
Case Report ◽  
Thyroid Gland ◽  
Ct Scan ◽  
Neuroendocrine Tumor ◽  
Radionuclide Therapy ◽  
Neuron Specific Enolase ◽  
Peptide Receptor Radionuclide Therapy ◽  
Left Lobe ◽  
Whole Body ◽  
Peptide Receptor

Introduction. Thyroid paraganglioma is a very rare malignant neuroendocrine tumor. Immunohistochemical features of thyroid paraganglioma are helpful for the diagnosis. Case report. A 69-year-old female came to hospital with the presence of a growing thyroid nodule of the left lobe. Ultrasonic neck examination showed 5 cm hypoechoic nodule in the left thyroid lobe. Thyroid scintigraphy showed a big cold nodule in the left lobe. Computed tomography (CT) scan showed left lobe thyroid tumor with tracheal deviation on the right site. Extended total thyroidectomy was done. Intraoperative consultation with the pathologist confirmed thyroid cancer. The pathologist diagnosed thyroid paraganglioma on the base of immuohistochemical investigation. This thyroid paraganglioma was positive for neuron-specific enolase, chomogranin A, synaptophysin, and S-100 protein highlighted the sustentacular cells. Tumor cells were nega-tive for thyroglobulin, epithelial membrane antigen, cytokeratin, calcitonin, and carcinoembryonic. After the surgery the patient was treated with chemotherapy, peptide receptor radionuclide therapy, and permanent TSH suppressive therapy. The patient was followed with measurements of thyroid hormone and serum neuron-specific enolase, chromogranin A level, every 6 months. Gastroscopy, colonoscopy, chest and abdomen CT scan as well as further tests (chest x-ray, ultrasound of the neck, and whole body octreotide scintigraphy) were done. No primary neuroendocrine tumor in digestive sistem or in the chest was found. After more than 3 years the patient has no evidence of the recurrent disease. Conclusion. Radical resection of thyroid paraganglioma, followed by chemotherapy and peptide receptor radionuclide therapy, should be considered the treatment of choice in patients with thyroid gland paraganglioma.

scholarly journals Dose Prediction Using a Three-Dimensional Convolutional Neural Network for Nasopharyngeal Carcinoma With Tomotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaoying Liu ◽  
Zhaocai Chen ◽  
Jinyuan Wang ◽  
Xiaoshen Wang ◽  
Baolin Qu ◽  
...  
Keyword(s):  
Neural Network ◽  
Nasopharyngeal Carcinoma ◽  
Prediction Model ◽  
Convolutional Neural Network ◽  
Patch Size ◽  
Organs At Risk ◽  
Whole Body ◽  
Patient Specific ◽  
Dose Prediction ◽  
The Mean

PurposeThis study focused on predicting 3D dose distribution at high precision and generated the prediction methods for nasopharyngeal carcinoma patients (NPC) treated with Tomotherapy based on the patient-specific gap between organs at risk (OARs) and planning target volumes (PTVs).MethodsA convolutional neural network (CNN) is trained using the CT and contour masks as the input and dose distributions as output. The CNN is based on the “3D Dense-U-Net”, which combines the U-Net and the Dense-Net. To evaluate the model, we retrospectively used 124 NPC patients treated with Tomotherapy, in which 96 and 28 patients were randomly split and used for model training and test, respectively. We performed comparison studies using different training matrix shapes and dimensions for the CNN models, i.e., 128 ×128 ×48 (for Model I), 128 ×128 ×16 (for Model II), and 2D Dense U-Net (for Model III). The performance of these models was quantitatively evaluated using clinically relevant metrics and statistical analysis.ResultsWe found a more considerable height of the training patch size yields a better model outcome. The study calculated the corresponding errors by comparing the predicted dose with the ground truth. The mean deviations from the mean and maximum doses of PTVs and OARs were 2.42 and 2.93%. Error for the maximum dose of right optic nerves in Model I was 4.87 ± 6.88%, compared with 7.9 ± 6.8% in Model II (p=0.08) and 13.85 ± 10.97% in Model III (p&lt;0.01); the Model I performed the best. The gamma passing rates of PTV60 for 3%/3 mm criteria was 83.6 ± 5.2% in Model I, compared with 75.9 ± 5.5% in Model II (p&lt;0.001) and 77.2 ± 7.3% in Model III (p&lt;0.01); the Model I also gave the best outcome. The prediction error of D95 for PTV60 was 0.64 ± 0.68% in Model I, compared with 2.04 ± 1.38% in Model II (p&lt;0.01) and 1.05 ± 0.96% in Model III (p=0.01); the Model I was also the best one.ConclusionsIt is significant to train the dose prediction model by exploiting deep-learning techniques with various clinical logic concepts. Increasing the height (Y direction) of training patch size can improve the dose prediction accuracy of tiny OARs and the whole body. Our dose prediction network model provides a clinically acceptable result and a training strategy for a dose prediction model. It should be helpful to build automatic Tomotherapy planning.

A Simple Method for the Evaluation of Internal Doses in Nuclear Medicine

1974 ◽  
Vol 13 (02) ◽  
pp. 193-206
Author(s):  
L. Conte ◽  
L. Mombelli ◽  
A. Vanoli
Keyword(s):  
Nuclear Medicine ◽  
Close Agreement ◽  
Whole Body ◽  
Simple Method ◽  
Rapid Estimation ◽  
Absorbed Doses ◽  
The Mean ◽  
The Individual ◽  
Estimation Of Risk

SummaryWe have put forward a method to be used in the field of nuclear medicine, for calculating internally absorbed doses in patients. The simplicity and flexibility of this method allow one to make a rapid estimation of risk both to the individual and to the population. In order to calculate the absorbed doses we based our procedure on the concept of the mean absorbed fraction, taking into account anatomical and functional variability which is highly important in the calculation of internal doses in children. With this aim in mind we prepared tables which take into consideration anatomical differences and which permit the calculation of the mean absorbed doses in the whole body, in the organs accumulating radioactivity, in the gonads and in the marrow; all this for those radionuclides most widely used in nuclear medicine. By comparing our results with dose obtained from the use of M.I.R.D.'s method it can be seen that when the errors inherent in these types of calculation are taken into account, the results of both methods are in close agreement.

Aktivitätskonzentration der vom Personal einer Radiojodtherapiestation eingeatmeten Luft

1987 ◽  
Vol 26 (03) ◽  
pp. 143-146 ◽  
Author(s):  
H. Fill ◽  
M. Oberladstätter ◽  
J. W. Krzesniak
Keyword(s):  
Nuclear Medicine ◽  
Length Of Stay ◽  
Activity Concentration ◽  
Threshold Value ◽  
Whole Body ◽  
Therapeutic Activity ◽  
External Radiation ◽  
Oral Application ◽  
Exhaled Air ◽  
The Mean

The mean activity concentration of1311 during inhalation by the nuclear medicine personnel was measured at therapeutic activity applications of 22 GBq (600 mCi) per week. The activity concentration reached its maximum in the exhaled air of the patients 2.5 to 4 hours after oral application. The normalized maximum was between 2 • 10−5 and 2 • 10−3 Bq-m−3 per administered Bq. The mean activity concentration of1311 inhaled by the personnel was 28 to 1300 Bq-m−3 (0.8 to 35 nCi-rrf−3). From this the1311 uptake per year was estimated to be 30 to 400 kBq/a (x̄ = 250, SD = 50%). The maximum permitted uptake from air per year is, according to the German and Austrian radiation protection ordinances 22/21 µiCi/a (= 8 • 105 Bq/a). At maximum 50% and, on the average, 30% of this threshold value are reached. The length of stay of the personnel in the patient rooms is already now limited to such an extent that 10% of the maximum permissible whole-body dose for external radiation is not exceeded. Therefore, increased attention should be paid also to radiation exposure by inhalation.

scholarly journals Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aman Chauhan ◽  
Satya Das ◽  
Rachel Miller ◽  
Laura Luque ◽  
Samuel N. Cheuvront ◽  
...  
Keyword(s):  
Amino Acid ◽  
Neuroendocrine Tumor ◽  
Gastrointestinal Symptoms ◽  
Retrospective Chart Review ◽  
Final Analysis ◽  
Acid Mixture ◽  
Tumor Patients ◽  
Short Gut Syndrome ◽  
Oral Rehydration ◽  
The Mean

Abstract Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. Methods A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. Results Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3–20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0–11). Conclusions Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.

scholarly journals Predictive and Prognostic Impact of Blood-Based Inflammatory Biomarkers in Patients with Gastroenteropancreatic Neuroendocrine Tumors Commencing Peptide Receptor Radionuclide Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 504
Author(s):  
Fiona Ohlendorf ◽  
Rudolf Werner ◽  
Christoph Henkenberens ◽  
Tobias Ross ◽  
Hans Christiansen ◽  
...  
Keyword(s):  
Treatment Response ◽  
Neuroendocrine Tumors ◽  
Radionuclide Therapy ◽  
Somatostatin Receptor ◽  
Peptide Receptor Radionuclide Therapy ◽  
Tumor Burden ◽  
Inflammatory Biomarkers ◽  
Whole Body ◽  
Prognostic Impact ◽  
Peptide Receptor

Tumor microenvironment inflammation contributes to the proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, and reduced treatment response. We aimed to evaluate the early predictive and prognostic significance of markers of systemic inflammation in patients receiving somatostatin-receptor targeted peptide receptor radionuclide therapy (PRRT). This retrospective observational cohort study included 33 patients with advanced gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) treated with PRRT. Pretreatment blood-based inflammatory biomarkers, e.g., Creactive protein levels (CRP), white blood cell count (WBC), and absolute neutrophil count (ANC), were documented and inflammation indexes, e.g., neutrophil-lymphocyte ratio (NLR) and Platelet × CRP multiplier (PCM), were calculated. Tumor burden was determined using [68Ga]GaDOTATATE PET/CT before enrollment and every 2 cycles thereafter until progression. Therapy response was assessed using RECIST 1.1, including its volumetric modification. Inflammatory biomarkers and inflammatory indexes demonstrated marked heterogeneity among patients, and were significantly higher in non-responders (e.g., CRP (P < 0.001), ANC (P = 0.002), and PCM (P < 0.001)). Change in whole-body tumor burden after two cycles of PRRT was significantly associated with CRP (P = 0.0157) and NLR (P = 0.0040) in multivariate regression analysis. A cut-off of 2.5 mg/L for CRP (AUC = 0.84, P = 0.001) revealed a significant outcome difference between patients with adversely high vs. low CRP (median PFS 508 days vs. not yet reached (HR = 4.52; 95% CI, 1.27 to 16.18; P = 0.02)). Tumor-driven systemic inflammatory networks may be associated with treatment response, change in tumor burden, and prognosis in patients with GEPNETs receiving PRRT.

scholarly journals Improved PET/MRI attenuation correction in the pelvic region using a statistical decomposition method on T2-weighted images

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Elin Wallstén ◽  
Jan Axelsson ◽  
Joakim Jonsson ◽  
Camilla Thellenberg Karlsson ◽  
Tufve Nyholm ◽  
...  
Keyword(s):  
Attenuation Correction ◽  
Research Study ◽  
Standardized Uptake Value ◽  
Ground Truth ◽  
Whole Body ◽  
Mr Images ◽  
Pelvic Region ◽  
Mri Scans ◽  
The Mean ◽  
Prostate Cancer Research

Abstract Background Attenuation correction of PET/MRI is a remaining problem for whole-body PET/MRI. The statistical decomposition algorithm (SDA) is a probabilistic atlas-based method that calculates synthetic CTs from T2-weighted MRI scans. In this study, we evaluated the application of SDA for attenuation correction of PET images in the pelvic region. Materials and method Twelve patients were retrospectively selected from an ongoing prostate cancer research study. The patients had same-day scans of [11C]acetate PET/MRI and CT. The CT images were non-rigidly registered to the PET/MRI geometry, and PET images were reconstructed with attenuation correction employing CT, SDA-generated CT, and the built-in Dixon sequence-based method of the scanner. The PET images reconstructed using CT-based attenuation correction were used as ground truth. Results The mean whole-image PET uptake error was reduced from − 5.4% for Dixon-PET to − 0.9% for SDA-PET. The prostate standardized uptake value (SUV) quantification error was significantly reduced from − 5.6% for Dixon-PET to − 2.3% for SDA-PET. Conclusion Attenuation correction with SDA improves quantification of PET/MR images in the pelvic region compared to the Dixon-based method.

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