Characterization of an intraperitoneal ovarian cancer xenograft model in nude rats using noninvasive microPET imaging

2007 ◽  
Vol 17 (2) ◽  
pp. 407-417 ◽  
Author(s):  
C. L. Zavaleta ◽  
W. T. Phillips ◽  
Y. C. Bradley ◽  
L. M. McMANUS ◽  
P. A. Jerabek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Nodes ◽  
Peritoneal Cavity ◽  
Imaging Modality ◽  
Xenograft Model ◽  
Tumor Model ◽  
Fdg Uptake ◽  
Tumor Bearing ◽  
Nude Rats ◽  
Biodistribution Data

MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose (18F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 μCi) of 18F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of 18F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of 18F-FDG throughout the peritoneal cavity of tumor rats (mean SUV = 4.64) compared with control rats (mean SUV = 1.03). Ascites gathered from tumor-bearing rats had increased 18F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. 18F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using 18F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model.

Effects of a soluble activin type 2B receptor Fc fusion protein (STM 217) in TOV-21G, a mouse xenograft model of clear cell ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2541-2541
Author(s):  
John Lu ◽  
Christopher M. Haqq ◽  
HQ Han
Keyword(s):  
Ovarian Cancer ◽  
Body Weight ◽  
Tumor Growth ◽  
Clear Cell ◽  
Phase 1 ◽  
Elevated Serum ◽  
Xenograft Model ◽  
Growth Reduction ◽  
Tumor Bearing ◽  
Mouse Xenograft Model

2541 Background: Response rate and survival with the clear cell subtype of ovarian cancer is has not been improved by the introduction of platinum and taxane chemotherapy. Elevated serum activin is associated with inferior ovarian cancer survival, suggesting that activin inhibition may provide a new treatment strategy. STM 217 (recombinant hu-sActR2B-Fc) is a potent (IC50 < 1nM) inhibitor of activin and myostatin signaling that was tested for anti-ovarian tumor activity. Methods: Athymic nude mice received TOV-21g (clear cell ovarian cancer model) xenografts in the abdominal flank region and after 14 days, weekly subcutaneous STM 217 was administered alone or in combination with 5-fluorouracil (5-FU). Mice were monitored for body weight and tumor volume. Results: After 52 days from tumor cell injection, STM 217 treatment resulted in a statistically significant 43% (p<0.0001) tumor growth reduction, versus the vehicle-treated tumor bearing group tested using ANOVA. In the combination efficacy experiment, 5-FU monotherapy resulted in a 47% (p<0.0001) tumor growth reduction, and the combination of STM217 and 5-FU together resulted in a 73% (p<0.0001) tumor growth reduction. During the course of the study, body weight of the mice receiving STM 217 increased by 26%, mice receiving STM 217 and 5-FU increased by 22%, while control tumor bearing mice receiving vehicle exhibited a 10% body weight loss. Conclusions: Our study demonstrates that inhibition of activin signaling by use of a ligand trap results in antitumor activity, both as a monotherapy, and that additive activity was observed in combination with chemotherapy. Increases in body weight were not impaired by concomitant administration of 5-FU chemotherapy. This study suggests that a phase 1 clinical trial of activin inhibition in metastatic ovarian cancer is warranted.

Identification of new lesion with disease progression in Ovarian cancer per RECIST 1.1.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18058-e18058
Author(s):  
Manish Sharma ◽  
Oliver Bohnsack ◽  
Rudresh Jarecha ◽  
Jayant Narang ◽  
Anitha Singareddy ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Nodes ◽  
Peritoneal Cavity ◽  
Survival Rates ◽  
Tumor Burden ◽  
Double Blind ◽  
Metastatic Colonization ◽  
Recist 1.1 ◽  
Peritoneal Spread

e18058 Background: Metastasis is the leading cause of ovarian cancer (OC) related death with more than 70% of OC patients diagnosed with metastasis with five-year survival rates below 45%. OC cells mainly metastasize within the peritoneal cavity at presentation and throughout the course of the disease in 85% of the patients which involves exfoliation from the primary tumor, followed by survival and transport in the peritoneal fluid and finally metastatic colonization of the organs within the peritoneal cavity. There is a tendency of conventional imaging to underestimate the frequency of peritoneal spread. The purpose of the study was to obtain the frequency of organ involvement in OC metastasis and identify the most common route of OC metastasis. Methods: Retrospective study and analysis of two randomized double-blind trials was performed in patients with OC. Data was analyzed from these studies using blinded independent central review using RECIST 1.1 involving a total of 895 subjects, 528 and 367 respectively. A double read with adjudication by independent radiologists was performed for each scan based on the RECIST 1.1 criteria. Baseline tumor burden was assessed for all subjects using RECIST 1.1 criteria. At follow-up visits, data was specifically analyzed for New lesions. The readers had to select New lesion location from a pre-defined location list from a drop-down menu. Data was tabulated with frequency of subjects with New lesion per each location. Results: With both studies combined involving 895 subjects, total subjects with new metastasis observed in decreasing order for various organs were peritoneum/omentum (406), lymph nodes (315), ascites (207), liver (94), pleural effusion (65), pelvis (52) & lung (56). Other less common locations for new metastasis was abdominal wall, pleural deposits, spleen, brain, retroperitoneum and adrenal. We also looked at the possibility of disagreement between 2 readers in identifying such lesions leading to progression as below. Conclusions: It can be concluded that subjects with ovarian cancer tend to develop metastasis leading to progression per RECIST 1.1 in peritoneum / omentum, lymph nodes, liver and lung. Due to significant variability in identification of such discrete, ill-defined and/or small nature of lesions, targeted awareness and training should be incorporated to improve clinical outcome. [Table: see text]

THE STUDY OF CIRCADIAN RHYTHMS IN OVARIAN CANCER RAT MODEL: IS THERE CONNECTION BETWEEN TUMOR DEVELOPMENT AND RHYTHMICITY DISRUPTION IN INTACT TISSUES?

2019 ◽  
Vol 65 (6) ◽  
pp. 889-897
Author(s):  
Galina Kireeva ◽  
Yekaterina Gubareva ◽  
Natalya Mityushkina ◽  
Andrey Panchenko ◽  
Mikhail Maydin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Circadian Rhythms ◽  
Tumor Cells ◽  
Clock Genes ◽  
Tumor Development ◽  
Tumor Model ◽  
Circadian Rhythmicity ◽  
Normal Tissues ◽  
Tumor Bearing

Considering emerging yet contradictory data on circadian rhythms disruption and its effects on tumor initiation and progression, we performed in vivo study to evaluate changes (if any) in clock genes expression in tumor compared to intact tissues as well as to see if tumor development affects normal tissues in tumor-bearing animals. The study was performed in 75 female Wistar rats, intraperitoneally transplanted ovarian cancer was used as a tumor model. Tumor-bearing rats had fragmented circadian rhythmicity of their locomotor activity compared to intact animals. No circadian rhythmicity in proliferation of tumor cells was detected. Precise proliferative rhythmicity was found in normal cells (intestinal epithelium) of intact rats, while significant disruption in such rhythmicity was observed in the same cells of tumor-bearing rats. Average clock genes (BMAL1, CLOCK, CRY1, PER2) expression rate was significantly reduced in tumor cells compared to intact tissues. The data from these experiments let us choosing 2 time points to perform chemotherapy in the following study where effects of chronochemotherapy will be evaluated.

Postlumpectomy loco-regional breast cancer therapy with liposomal therapeutic agents: Retention and distribution in nude rats

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11562-e11562
Author(s):  
S. Li ◽  
B. Goins ◽  
W. T. Phillips ◽  
M. Saenz ◽  
P. Otto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Xenograft Model ◽  
Therapeutic Agents ◽  
Surgical Removal ◽  
Post Mortem ◽  
Surface Charges ◽  
Nude Rats ◽  
Anionic Liposomes

e11562 Background: Post-lumpectomy loco-regional radiation therapy, such as brachytherapy, has been shown to decrease breast cancer recurrence and increase patient survival. Limitations of current brachytherapy are the relatively high radiation absorbed dose delivered to normal breast and the inability to treat potentially involved lymph nodes. Locally administered liposomes are being investigated for delivery of drugs and therapeutic radionuclides. We propose a new post-lumpectomy loco-regional therapy with liposome-carried therapeutic agents. To investigate, radiolabeled liposomes were injected into the surgical cavity of a nude rat model one day following surgical removal of the breast tumor, and in vivo retention and distribution were monitored with nuclear imaging and post- mortem dissection. Methods: Six liposome formulations containing 0.2% molar ratio Rhodamine B-lipid and cationic, neutral, or anionic surface charges were manufactured at diameters of 400 or 100 nm and characterized. Breast cancer xenograft model in female nude rats was set up by inoculating MDA-MB-231 cells into the fat pad of the left breast of each rat. When tumor volumes reached 1.9 cm3 on average, the majority of each tumor was surgically removed, leaving ∼0.05 cm3 tumor tissue in the cavity. Then, each rat (3–4 rats/group) was intracavitarily injected with 0.5 ml of 99mTc-liposomes (4 mCi., 30 mg total lipids/kg body weight). In vivo distribution of 99mTc-activity was measured with planar gamma camera and SPECT imaging at various times. Post-mortem stereo fluorescent images of surgical cavity and the surrounding lymph nodes at 44 h were acquired. Results: All 99mTc-liposome formulations had approximately ≥ 50% retention in the surgical cavity at 44 h after injection. 99mTc-anionic liposomes of 100 nm diameter had an optimal lymph node targeting with ∼6%/g tissue in the surrounding lymph nodes at 44 h. Fluorescence imaging of the liposomes clearly showed their clearance through surrounding lymphatics and retention in lymph nodes. Conclusions: Anionic liposomes of 100 nm diameter are promising carriers for the simultaneous treatment of the surgical cavity and its draining lymph nodes. No significant financial relationships to disclose.

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

2019 ◽  
Vol 19 (11) ◽  
pp. 1382-1387
Author(s):  
Ahmet M. Şenışık ◽  
Çiğdem İçhedef ◽  
Ayfer Y. Kılçar ◽  
Eser Uçar ◽  
Kadir Arı ◽  
...  
Keyword(s):  
High Performance ◽  
The Body ◽  
Biological Behavior ◽  
In Vivo Evaluation ◽  
Radiolabeled Peptides ◽  
Tumor Bearing ◽  
Biodistribution Data ◽  
Good Accordance ◽  
Rapid Clearance

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

scholarly journals Prognostic significance of bone marrow FDG uptake in patients with gynecological cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kotaro Shimura ◽  
Seiji Mabuchi ◽  
Naoko Komura ◽  
Eriko Yokoi ◽  
Katsumi Kozasa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bone Marrow ◽  
Poor Prognosis ◽  
Gynecological Cancer ◽  
Prognostic Significance ◽  
Standardized Uptake Value ◽  
Suppressor Cells ◽  
Underlying Mechanism ◽  
Fdg Uptake

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

scholarly journals Mannan-Based Nanodiagnostic Agents for Targeting Sentinel Lymph Nodes and Tumors

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 146
Author(s):  
Markéta Jirátová ◽  
Andrea Gálisová ◽  
Maria Rabyk ◽  
Eva Sticová ◽  
Martin Hrubý ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Intraoperative Imaging ◽  
Tumor Model ◽  
Intercellular Adhesion Molecule ◽  
Internal Organs ◽  
Polymer Carriers ◽  
Polymer Conjugates ◽  
Imaging Tool ◽  
Imaging Probes

Early detection of metastasis is crucial for successful cancer treatment. Sentinel lymph node (SLN) biopsies are used to detect possible pathways of metastasis spread. We present a unique non-invasive diagnostic alternative to biopsy along with an intraoperative imaging tool for surgery proven on an in vivo animal tumor model. Our approach is based on mannan-based copolymers synergistically targeting: (1) SLNs and macrophage-infiltrated solid tumor areas via the high-affinity DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) receptors and (2) tumors via the enhanced permeability and retention (EPR) effect. The polymer conjugates were modified with the imaging probes for visualization with magnetic resonance (MR) and fluorescence imaging, respectively, and with poly(2-methyl-2-oxazoline) (POX) to lower unwanted accumulation in internal organs and to slow down the biodegradation rate. We demonstrated that these polymer conjugates were successfully accumulated in tumors, SLNs and other lymph nodes. Modification with POX resulted in lower accumulation not only in internal organs, but also in lymph nodes and tumors. Importantly, we have shown that mannan-based polymer carriers are non-toxic and, when applied to an in vivo murine cancer model, and offer promising potential as the versatile imaging agents.

Association between PD-L1 expression and 18F-FDG uptake in ovarian cancer

2021 ◽  
Vol 35 (4) ◽  
pp. 415-420
Author(s):  
Yun Jung Choi ◽  
KwanHyeong Jo ◽  
Sang Hyun Hwang ◽  
YongHyu Jeong ◽  
Jung-Yun Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fdg Uptake ◽  
18F Fdg
Sign in / Sign up

Export Citation Format

Share Document