scholarly journals Porous Silicon as a Platform for Radiation Theranostics Together with a Novel RIB-Based Radiolanthanoid

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ulrika Jakobsson ◽  
Ermei Mäkilä ◽  
Anu J. Airaksinen ◽  
Osku Alanen ◽  
Asenath Etilé ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Porous Silicon ◽  
Ex Vivo ◽  
Ion Beam ◽  
Ion Beams ◽  
Radioactive Ion Beams ◽  
Mesoporous Silicon ◽  
Main Site ◽  
The Stability

Mesoporous silicon (PSi) is biocompatible and tailorable material with high potential in drug delivery applications. Here, we report of an evaluation of PSi as a carrier platform for theranostics by delivering a radioactive ion beam- (RIB-) based radioactive lanthanoid into tumors in a mouse model of prostate carcinoma. Thermally hydrocarbonized porous silicon (THCPSi) wafers were implanted with 159Dy at the facility for radioactive ion beams ISOLDE located at CERN, and the resulting [159Dy]THCPSi was postprocessed into particles. The particles were intratumorally injected into mice bearing prostate cancer xenografts. The stability of the particles was studied in vivo, followed by ex vivo biodistribution and autoradiographic studies. We showed that the process of producing radionuclide-implanted PSi particles is feasible and that the [159Dy]THCPSi particles stay stable and local inside the tumor over seven days. Upon release of 159Dy from the particles, the main site of accumulation is in the skeleton, which is in agreement with previous studies on the biodistribution of dysprosium. We conclude that THCPSi particles are a suitable platform together with RIB-based radiolanthanoids for theranostic purposes as they are retained after administration inside the tumor and the radiolanthanoid remains embedded in the THCPSi.

scholarly journals Yttrium Oxide Freeze-Casts: Target Materials for Radioactive Ion Beams

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2864
Author(s):  
Eva Kröll ◽  
Miriana Vadalà ◽  
Juliana Schell ◽  
Simon Stegemann ◽  
Jochen Ballof ◽  
...  
Keyword(s):  
Pore Structure ◽  
Yttrium Oxide ◽  
Ion Beam ◽  
Isotope Separation ◽  
Target Material ◽  
Ion Beams ◽  
Radioactive Isotopes ◽  
Solid Loading ◽  
Radioactive Ion Beams ◽  
Freeze Casting

Highly porous yttrium oxide is fabricated as ion beam target material in order to produce radioactive ion beams via the Isotope Separation On Line (ISOL) method. Freeze casting allows the formation of an aligned pore structure in these target materials to improve the isotope release. Aqueous suspensions containing a solid loading of 10, 15, and 20 vol% were solidified with a unidirectional freeze-casting setup. The pore size and pore structure of the yttrium oxide freeze-casts are highly affected by the amount of solid loading. The porosity ranges from 72 to 84% and the crosslinking between the aligned channels increases with increasing solid loading. Thermal aging of the final target materials shows that an operation temperature of 1400 °C for 96 h has no significant effect on the microstructure. Thermo-mechanical calculation results, based on a FLUKA simulation, are compared to measured compressive strength and forecast the mechanical integrity of the target materials during operation. Even though they were developed for the particular purpose of the production of short-lived radioactive isotopes, the yttria freeze-cast scaffolds can serve multiple other purposes, such as catalyst support frameworks or high-temperature fume filters.

scholarly journals Conditionally Reprogrammed Cells from Patient-Derived Xenograft to Model Neuroendocrine Prostate Cancer Development

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1398 ◽  
Author(s):  
Xinpei Ci ◽  
Jun Hao ◽  
Xin Dong ◽  
Hui Xue ◽  
Rebecca Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Ex Vivo ◽  
Cancer Cell Line ◽  
Marker Genes ◽  
Patient Derived Xenograft ◽  
Pdx Model ◽  
Neuroendocrine Prostate Cancer ◽  
Parental Tumor

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. It develops mainly via NE transdifferentiation of prostate adenocarcinoma in response to androgen receptor (AR)-inhibition therapy. The study of NEPC development has been hampered by a lack of clinically relevant models. We previously established a unique and first-in-field patient-derived xenograft (PDX) model of adenocarcinoma (LTL331)-to-NEPC (LTL331R) transdifferentiation. In this study, we applied conditional reprogramming (CR) culture to establish a LTL331 PDX-derived cancer cell line named LTL331_CR_Cell. These cells retain the same genomic mutations as the LTL331 parental tumor. They can be continuously propagated in vitro and can be genetically manipulated. Androgen deprivation treatment on LTL331_CR_Cells had no effect on cell proliferation. Transcriptomic analyses comparing the LTL331_CR_Cell to its parental tumor revealed a profound downregulation of the androgen response pathway and an upregulation of stem and basal cell marker genes. The transcriptome of LTL331_CR_Cells partially resembles that of post-castrated LTL331 xenografts in mice. Notably, when grafted under the renal capsules of male NOD/SCID mice, LTL331_CR_Cells spontaneously gave rise to NEPC tumors. This is evidenced by the histological expression of the NE marker CD56 and the loss of adenocarcinoma markers such as PSA. Transcriptomic analyses of the newly developed NEPC tumors further demonstrate marked enrichment of NEPC signature genes and loss of AR signaling genes. This study provides a novel research tool derived from a unique PDX model. It allows for the investigation of mechanisms underlying NEPC development by enabling gene manipulations ex vivo and subsequent functional evaluations in vivo.

Forming Antifouling Organic Multilayers on Porous Silicon Rugate Filters Towards In Vivo/Ex Vivo Biophotonic Devices

2007 ◽  
Vol 17 (15) ◽  
pp. 2884-2890 ◽  
Author(s):  
K. A. Kilian ◽  
T. Böcking ◽  
S. Ilyas ◽  
K. Gaus ◽  
W. Jessup ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Ex Vivo

Leveraging RB status to define therapy for castrate-resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 96-96
Author(s):  
Renee de Leeuw ◽  
Clay de Comstock ◽  
Daniela de Pollutri ◽  
Matthew Joseph Schiewer ◽  
Stephen J Ciment ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Kinase Inhibitors ◽  
Ex Vivo ◽  
Tissue Samples ◽  
Ki67 Staining ◽  
Cell Architecture ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

96 Background: Loss of retinoblastoma (RB) tumor suppressor is overrepresented in castrate-resistant prostate cancer (CRPC) compared to primary PCa. We previously showed using analyses of human tissue and in vitro and in vivo modeling that RB constrains androgen receptor (AR) function, and that loss of RB is sufficient promote resistance to castration and AR antagonists. Thus, novel strategies are needed to treat RB-deficient tumor. By contrast, in tumors retaining RB, suppressing enhancing RB activity would be of therapeutic advantage, and may be accomplished through next-generation Cdk4/6 inhibitors. Methods: Stable isogenic pairs of prostate cancer cell lines either retaining RB or RB depleted (by shRNA) were assessed in vitro and in xenografts for response to Cdk4/6 kinase inhibitors or the cabazitaxel. In addition, using an ex vivo explant assay, fresh tumor tissue samples from radical prostatectomy were exposed to the Cdk4/6 inhibitor or cabazitaxel for up to 7 days, and evaluated by IHC for Ki67, Caspase-3, and AR. Results: Cdk4/6 inhibition blocks tumor cell proliferation dependent on RB status. This was further confirmed ex vivo, as evidenced by a marked reduction in Ki67 staining in Cdk4/6 inhibitor treated explant tissue from two prostate cancer patients. Conversely, in vitro studies revealed a modest sensitization of RB-depleted tumors to cabazitaxel that was dramatically enhanced in vivo and after castration. Cabazitaxel, like docetaxel, targets the cell architecture and induces cell death, but also induces a distinct gene expression profile that may partially explain efficacy in docetaxel-resistant tumors. Neither taxane showed affects on AR nuclear localization using in vivoor explant studies. Conclusions: These results strongly support our hypothesis that RB status can be used as a metric to define therapeutic response to cabazitaxel, as such that loss of RB function induces sensitization taxanes, whereas RB proficient tumors give an enhanced response to Cdk4/6 kinase inhibitors.

scholarly journals MINDIN secretion by prostate tumors induces premetastatic changes in bone via β-catenin

2020 ◽  
Vol 27 (7) ◽  
pp. 441-456
Author(s):  
Juan A Ardura ◽  
Luis Álvarez-Carrión ◽  
Irene Gutiérrez-Rojas ◽  
Peter A Friedman ◽  
Arancha R Gortázar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Tumor Cell ◽  
Ex Vivo ◽  
Prostate Tumor ◽  
Tumor Cell Adhesion ◽  
Prostate Tumors ◽  
Cell Homing

Bone metastases are common in advanced prostate cancer patients, but mechanisms by which specific pro-metastatic skeletal niches are formed before tumor cell homing are unclear. We aimed to analyze the effects of proteins secreted by primary prostate tumors on the bone microenvironment before the settlement and propagation of metastases. Here, using an in vivo pre-metastatic prostate cancer model based on the implantation of prostate adenocarcinoma TRAMP-C1 cells in immunocompetent C57BL/6 mice, we identify MINDIN as a prostate tumor secreted protein that induces bone microstructural and bone remodeling gene expression changes before tumor cell homing. Associated with these changes, increased tumor cell adhesion to the endosteum ex vivo and to osteoblasts in vitro was observed. Furthermore, MINDIN promoted osteoblast proliferation and mineralization and monocyte expression of osteoclast markers. β-catenin signaling pathway revealed to mediate MINDIN actions on osteoblast gene expression but failed to affect MINDIN-induced adhesion to prostate tumor cells or monocyte differentiation to osteoclasts. Our study evidences that MINDIN secretion by primary prostate tumors creates a favorable bone environment for tumor cell homing before metastatic spread.

scholarly journals Development and Optimization of Proniosomal Gel Containing Etodolac: In-vitro, Ex-vivo and In-vivo Evaluation

2021 ◽  
Vol 62 (3) ◽  
pp. 290-304
Author(s):  
Moreshwar Patil ◽  
Prashant Pandit ◽  
Pavan Udavant ◽  
Sandeep Sonawane ◽  
Deepak Bhambere
Keyword(s):  
Drug Release ◽  
Zeta Potential ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
In Vivo Evaluation ◽  
Vesicle Size ◽  
Skin Delivery ◽  
The Stability

Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation. Method: In this work we used coacervation-phase separation method for the development of etodolac loaded vesicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study. Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel. Conclusion: Proniosomal gel formulation was stable and could enhance skin delivery of etodolac because of excellent permeation capability of vesicular system.

scholarly journals A DROP-IN Beta Probe for Robot-Assisted 68Ga-PSMA Radioguided Surgery: First Ex Vivo Technology Evaluation Using Prostate Cancer Specimens

2020 ◽  
Author(s):  
Francesco Collamati ◽  
Matthias van OOsterom ◽  
Micol De Simoni ◽  
Riccardo Faccini ◽  
Marta Fischetti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Ex Vivo ◽  
Gamma Probe ◽  
Beta Particle ◽  
Radioguided Surgery ◽  
Robot Assisted ◽  
Psma Pet ◽  
Positive Lymph Nodes

Abstract Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET-isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET-tracers during robot-assisted tumor-receptor-targeted. In this study, we’ve engineered and validated the performance of a novel DROP-IN beta-particle (DROP-INb) detector.Methods: Seven prostate cancer patients with PSMA-PET positive tumors received an additional intraoperative injection of ~70 MBq 68Ga-PSMA-11, followed by robot-assisted prostatectomy and extended pelvic lymph node dissection. The surgical specimens from these procedures were used to validate the performance of our DROP-INb probe prototype, with merged a scintillating detector with a housing optimized for a 12 mm trocar and prograsp instruments. Results: After optimization of the detector and probe housing via Monte Carlo simulations, the resulting DROP-INb probe prototype was tested in a robotic setting. In the ex vivo setting, the probe – positioned by the robot- was able to identify 68Ga-PSMA-11 containing hot-spots in the surgical specimens: signal-to-background (S/B) was > 5 when pathology confirmed that the tumor was located <1 mm below the specimen surface. 68Ga-PSMA-11 containing (and PET positive) lymph nodes, as found in two patients, were also confirmed with the DROP-INb probe (S/B>3). The rotational freedom of the DROP-IN design and the ability to manipulate the probe with the prograsp tool allowed the surgeon to perform autonomous beta tracing. Conclusions: This study demonstrates the feasibility of beta-radioguided surgery in a robotic context by means of a DROP-INb detector. When translated to an in vivo setting in the future, this technique could provide a valuable tool in detecting tumor remnants on the prostate surface and in confirmation of PSMA-PET positive lymph nodes.

Sign in / Sign up

Export Citation Format

Share Document