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Pancreatic Neoplasms: HELP
Articles by Marion de Jong
Based on 7 articles published since 2010
(Why 7 articles?)

Between 2010 and 2020, Marion de Jong wrote the following 7 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review Translational molecular imaging in exocrine pancreatic cancer. 2018

Cornelissen, Bart / Knight, James C / Mukherjee, Somnath / Evangelista, Laura / Xavier, Catarina / Caobelli, Federico / Del Vecchio, Silvana / Rbah-Vidal, Latifa / Barbet, Jacques / de Jong, Marion / van Leeuwen, Fijs W B. ·CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, UK. bart.cornelissen@oncology.ox.ac.uk. · CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, Oxford University, Oxford, UK. · Istituto Oncologico Veneto I.R.C.C.S., Padova, Italy. · Vrije Universiteit Brussel, Brussels, Belgium. · Department of Radiology, Universitätsspital Basel, Basel, Switzerland. · Universita' degli Studi di Napoli "Federico II", Naples, Italy. · CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France. · Department of Radiology & Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands. · Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. ·Eur J Nucl Med Mol Imaging · Pubmed #30225616.

ABSTRACT: Effective treatment for pancreatic cancer remains challenging, particularly the treatment of pancreatic ductal adenocarcinoma (PDAC), which makes up more than 95% of all pancreatic cancers. Late diagnosis and failure of chemotherapy and radiotherapy are all too common, and many patients die soon after diagnosis. Here, we make the case for the increased use of molecular imaging in PDAC preclinical research and in patient management.

2 Review Treatment of gastroenteropancreatic neuroendocrine tumors with peptide receptor radionuclide therapy. 2013

van Vliet, Esther I / Teunissen, Jaap J M / Kam, Boen L R / de Jong, Marion / Krenning, Eric P / Kwekkeboom, Dik J. ·Department of Nuclear Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. e.i.vanvliet@erasmusmc.nl ·Neuroendocrinology · Pubmed #22237390.

ABSTRACT: The primary treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs) is surgery with curative intent or debulking of the tumor mass. In case of metastatic disease, cytoreductive options are limited. A relatively new therapeutic modality, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs, is currently available in a number of mostly European centers. Complete and partial responses obtained after treatment with [90Y-DOTA0,Tyr3]octreotide are in the same range as after treatment with [177Lu-DOTA0,Tyr3]octreotate (i.e. 10-30%). However, significant nephrotoxicity has been observed after treatment with [90Y-DOTA0,Tyr3]octreotide. Options to improve PRRT may include combinations of radioactive labeled somatostatin analogs, intra-arterial administration, and the use of radiosensitizing drugs combined with PRRT. Other therapeutic applications of PRRT may include additional therapy cycles in patients with progressive disease after benefit from initial therapy, PRRT in adjuvant or neoadjuvant setting, or PRRT combined with new targeted therapies, such as sunitinib or everolimus. Randomized clinical trials comparing PRRT with other treatment modalities, or comparing various radioactive labeled somatostatin analogs should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs.

3 Article [(111)In-DTPA]octreotide tumor uptake in GEPNET liver metastases after intra-arterial administration: an overview of preclinical and clinical observations and implications for tumor radiation dose after peptide radionuclide therapy. 2014

Pool, Stefan E / Kam, Boen L R / Koning, Gerben A / Konijnenberg, Mark / Ten Hagen, Timo L M / Breeman, Woulter A P / Krenning, Eric P / de Jong, Marion / van Eijck, Casper H J. ·1 Department of Nuclear Medicine, Erasmus MC , Rotterdam, The Netherlands . ·Cancer Biother Radiopharm · Pubmed #24820805.

ABSTRACT: AIMS: With the aim to improve peptide receptor radionuclide therapy effects in patients with gastroenteropancreatic neuroendocrine tumor (GEPNET) liver metastases we explored the effect of intra-arterial (IA) administration of [(111)In-DTPA]octreotide ((111)In-DTPAOC) on tumor uptake in an animal model and in a patient study. METHODS: Preclinical study: After administering (111)In-DTPAOC intra-venously (IV) or IA, biodistribution studies were performed in rats with a hepatic somatostatin receptor subtype 2 (sst2)-positive tumor. Clinical study: 3 patients with neuroendocrine liver metastases were injected twice with (111)In-DTPAOC. The first injection was given IV, and 2 weeks later, the second was injected IA (hepatic artery). Planar images of the abdomen were made up to 72 hours after injection. Blood samples were taken and urine was collected. Pharmacokinetic modeling was performed on the IV and IA data of the same patient. Based on this model, additional (177)Lu dosimetry calculations for IV and IA administrations were performed. RESULTS: The preclinical study showed a two-fold higher (111)In-DTPAOC tumor uptake after IA administration than after IV injection. Patient data showed a large variability in radioactivity increment in liver metastases after IA administration compared with IV administration. Renal radioactivity was not significantly lower after IA administration; (177)Lu dosimetry simulations in 1 patient using a maximum kidney radiation dose of 23 Gy showed IA administration resulted in a mean increase in tumor radiation dose of 2.9-fold. CONCLUSION: Preclinical and clinical data both indicate that IA administration of radiolabeled somatostatin analogs via the hepatic artery can significantly increase radionuclide uptake in GEPNET, sst2-positive, liver metastases up to 72 hours postinjection, although the effect of IA administration can differ between patients.

4 Article Can DCE-MRI explain the heterogeneity in radiopeptide uptake imaged by SPECT in a pancreatic neuroendocrine tumor model? 2013

Bol, Karin / Haeck, Joost C / Groen, Harald C / Niessen, Wiro J / Bernsen, Monique R / de Jong, Marion / Veenland, Jifke F. ·Biomedical Imaging Group Rotterdam, Departments of Radiology and Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands ; Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands ; Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. ·PLoS One · Pubmed #24116203.

ABSTRACT: Although efficient delivery and distribution of treatment agents over the whole tumor is essential for successful tumor treatment, the distribution of most of these agents cannot be visualized. However, with single-photon emission computed tomography (SPECT), both delivery and uptake of radiolabeled peptides can be visualized in a neuroendocrine tumor model overexpressing somatostatin receptors. A heterogeneous peptide uptake is often observed in these tumors. We hypothesized that peptide distribution in the tumor is spatially related to tumor perfusion, vessel density and permeability, as imaged and quantified by DCE-MRI in a neuroendocrine tumor model. Four subcutaneous CA20948 tumor-bearing Lewis rats were injected with the somatostatin-analog (111)In-DTPA-Octreotide (50 MBq). SPECT-CT and MRI scans were acquired and MRI was spatially registered to SPECT-CT. DCE-MRI was analyzed using semi-quantitative and quantitative methods. Correlation between SPECT and DCE-MRI was investigated with 1) Spearman's rank correlation coefficient; 2) SPECT uptake values grouped into deciles with corresponding median DCE-MRI parametric values and vice versa; and 3) linear regression analysis for median parameter values in combined datasets. In all tumors, areas with low peptide uptake correlated with low perfusion/density/ /permeability for all DCE-MRI-derived parameters. Combining all datasets, highest linear regression was found between peptide uptake and semi-quantitative parameters (R(2)>0.7). The average correlation coefficient between SPECT and DCE-MRI-derived parameters ranged from 0.52-0.56 (p<0.05) for parameters primarily associated with exchange between blood and extracellular extravascular space. For these parameters a linear relation with peptide uptake was observed. In conclusion, the 'exchange-related' DCE-MRI-derived parameters seemed to predict peptide uptake better than the 'contrast amount- related' parameters. Consequently, fast and efficient diffusion through the vessel wall into tissue is an important factor for peptide delivery. DCE-MRI helps to elucidate the relation between vascular characteristics, peptide delivery and treatment efficacy, and may form a basis to predict targeting efficiency.

5 Article mTOR inhibitor RAD001 promotes metastasis in a rat model of pancreatic neuroendocrine cancer. 2013

Pool, Stefan E / Bison, Sander / Koelewijn, Stuart J / van der Graaf, Linda M / Melis, Marleen / Krenning, Eric P / de Jong, Marion. ·Department of Nuclear Medicine and Radiology, Erasmus MC, Rotterdam, The Netherlands. s.pool@erasmusmc.nl ·Cancer Res · Pubmed #23149918.

ABSTRACT: Inhibition of mTOR is commonly considered a valid target in cancer treatment, but this assertion does not address effects on the immune microenvironment that may be detrimental to cancer treatment. Here we show how administration of the mTOR inhibitor RAD001 (everolimus) results in the occurrence of distant metastasis in a rat model of pancreatic cancer. RAD001 was administered twice weekly for 4.5 weeks as a single treatment or combined with [(177)Lu-DOTA,Tyr3]octreotate ((177)Lu-DOTATATE), where the latter targets the somatostatin receptor-2. The hypothesized synergistic therapeutic effect of RAD001 combined with (177)Lu-DOTATATE was, however, not observed in our experiments. The combination was shown to be less effective than (177)Lu-DOTATATE alone. Unexpectedly, tumor metastasis was observed in 77% of the subjects treated with RAD001, either alone or as part of the combination treatment. This was a striking effect, because metastasis did not occur in control or (177)Lu-DOTATATE-treated animals, including those where the primary tumor was surgically removed. These findings may be important clinically among noncompliant patients or patients that discontinue RAD001 therapy because of adverse effects.

6 Article Multimodality imaging of somatostatin receptor-positive tumors with nuclear and bioluminescence imaging. 2012

Pool, Stefan E / ten Hagen, Timo L M / Koelewijn, Stuart / de Jong, Marion / Koning, Gerben A. ·Department of Surgery, Erasmus MC, Rotterdam, the Netherlands. s.pool@erasmusmc.nl ·Mol Imaging · Pubmed #22418025.

ABSTRACT: Multimodal bioluminescence (BLI) and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were investigated as means to monitor somatostatin receptor subtype 2 (SST2)-positive neuroendocrine tumors as both a subcutaneously implanted and a liver metastasis animal model in mice and rats. Ultimately, such a model will be of use for studying SST2-targeted peptide receptor radionuclide therapy (PRRT). CA20948 cells were transfected with a green fluorescent protein/luciferase plasmid construct. Cells were inoculated subcutaneously in the shoulder of nude mice: nontransfected cells in the left shoulder and transfected cells in the right shoulder. BLI, SPECT/CT imaging, biodistribution analysis, and ex vivo autoradiography of the tumors were performed. BLI and SPECT/CT imaging were also performed on an intrahepatic tumor model in the rat. Caliper volume measurement of transfected tumors could be correlated with BLI measurements (R2 = .76). SPECT/CT imaging showed high levels of accumulation of 111In-DTPA-octreotide in control and transfected tumors, which was confirmed by biodistribution analysis and autoradiography. Subcapsular inoculation of transfected cells in rat liver resulted in an intrahepatic tumor, which could be visualized by both SPECT/CT and BLI. Transfection of CA20948 tumor cells did not alter the growth properties of the cell line or the expression of SST2. Transfected tumors could be clearly visualized by BLI and SPECT/CT imaging. The transfected SST2-positive tumor cell line could represent a novel preclinical model for tumor monitoring in studies that aim at further optimizing PRRT for neuroendocrine tumors.

7 Article Facilitating tumor functional assessment by spatially relating 3D tumor histology and in vivo MRI: image registration approach. 2011

Alic, Lejla / Haeck, Joost C / Bol, Karin / Klein, Stefan / van Tiel, Sandra T / Wielepolski, Piotr A / de Jong, Marion / Niessen, Wiro J / Bernsen, Monique / Veenland, Jifke F. ·Biomedical Imaging Group Rotterdam, Department of Radiology and Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands. LejlaResearch@gmail.com ·PLoS One · Pubmed #21897840.

ABSTRACT: BACKGROUND: Magnetic resonance imaging (MRI), together with histology, is widely used to diagnose and to monitor treatment in oncology. Spatial correspondence between these modalities provides information about the ability of MRI to characterize cancerous tissue. However, registration is complicated by deformations during pathological processing, and differences in scale and information content. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a methodology for establishing an accurate 3D relation between histological sections and high resolution in vivo MRI tumor data. The key features of the methodology are: 1) standardized acquisition and processing, 2) use of an intermediate ex vivo MRI, 3) use of a reference cutting plane, 4) dense histological sampling, 5) elastic registration, and 6) use of complete 3D data sets. Five rat pancreatic tumors imaged by T2*-w MRI were used to evaluate the proposed methodology. The registration accuracy was assessed by root mean squared (RMS) distances between manually annotated landmark points in both modalities. After elastic registration the average RMS distance decreased from 1.4 to 0.7 mm. The intermediate ex vivo MRI and the reference cutting plane shared by all three 3D images (in vivo MRI, ex vivo MRI, and 3D histology data) were found to be crucial for the accurate co-registration between the 3D histological data set and in vivo MRI. The MR intensity in necrotic regions, as manually annotated in 3D histology, was significantly different from other histologically confirmed regions (i.e., viable and hemorrhagic). However, the viable and the hemorrhagic regions showed a large overlap in T2(*)-w MRI signal intensity. CONCLUSIONS: The established 3D correspondence between tumor histology and in vivo MRI enables extraction of MRI characteristics for histologically confirmed regions. The proposed methodology allows the creation of a tumor database of spatially registered multi-spectral MR images and multi-stained 3D histology.