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Theranostic prostate

Hooman Yari, Gregory Nkepang, Vibhudutta Awasthi
Prostate specific membrane antigen (PSMA) is a marker for diagnosis and targeted delivery of therapeutics to advanced/metastasized prostate cancer. We report a liposome-based system for theranostic delivery to PSMA-expressing (PSMA⁺) LNCaP cells. A lipopolymer (P³) comprising of PSMA ligand (PSMAL), polyethylene glycol (PEG2000 ), and palmitate was synthesized and post-inserted into the surface of preformed liposomes. These P³-liposomes were loaded with doxorubicin and radiolabeled with 99m Tc radionuclide to study their theranostic characteristics...
March 5, 2019: Materials
Monira Sarkis, Esther Ghanem, Kamil Rahme
Prostate cancer (PCa) has remarkably emerged as a prominent disease in the face of the male population. Conventional treatments like prostatectomy or radiation can be curative only if PCa is diagnosed at an early stage. In the field of targeted therapy, a bevy of novel therapeutic approaches have left a landmark in PCa treatment and have proven to extend survival via distinct modes of actions. Nanotherapy has started to take root and has become the hype of the century by virtue of its abundant advantages. Scientists have invested a great deal of interest in the development of nanostructures such as gold nanoparticles (AuNPs), which hold particularly great hope for PCa theranostics...
February 23, 2019: International Journal of Molecular Sciences
Rudolf A Werner, Ralph Bundschuh, Lena Bundschuh, Stefano Fanti, Mehrbod S Javadi, Takahiro Higuchi, Alexander Weich, Kenneth J Pienta, Andreas K Buck, Martin G Pomper, Michael A Gorin, Ken Herrmann, Constantin Lapa, Steven P Rowe
Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction...
February 22, 2019: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Alondra Escudero-Castellanos, Blanca Ocampo-García, Guillermina Ferro-Flores, Clara Santos-Cuevas, Enrique Morales-Ávila, Myrna Luna-Gutiérrez, Keila Isaac-Olivé
BACKROUND: Human tumors show intrinsic heterogeneity and changes in phenotype during disease progression, which implies different expression levels of cell surface receptors. The research on new heterodimeric lutetium-177 (Lu)-radiopharmaceuticals interacting with two different targets on tumor cells is a strategy for improvement of radiotheranostic performance. This study aimed to synthesize and characterize the Lu-DOTA-PSMA(inhibitor)-Lys-bombesin (Lu-DOTA-iPSMA-Lys-BN) heterodimer and to evaluate its potential to target prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPr) overexpressed in prostate cancer...
March 2019: Nuclear Medicine Communications
Alexander Heinzel, Dima Boghos, Felix M Mottaghy, Florian Gaertner, Markus Essler, Dirk von Mallek, Hojjat Ahmadzadehfar
PURPOSE: To evaluate the use of 68 Ga-PSMA PET/CT for monitoring response to 177 Lu-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with 177 Lu-PSMA-617 and whose records included 68 Ga-PSMA PET/CT imaging before the first and after the third or fourth treatment cycle...
January 29, 2019: European Journal of Nuclear Medicine and Molecular Imaging
Federica Bessone, Monica Argenziano, Giorgio Grillo, Benedetta Ferrara, Stefania Pizzimenti, Giuseppina Barrera, Giancarlo Cravotto, C Guiot, Ilaria Stura, Roberta Cavalli, Chiara Dianzani
Preventing recurrences and metastasis of Prostate Cancer after prostatectomy by administering adjuvant therapies is a quite controversial issue. In addition to effectiveness, absence of side effects and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 days, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way...
January 17, 2019: Nanotechnology
Catarina Oliveira Silva, Jacinta Oliveira Pinho, Joana Margarida Lopes, António J Almeida, Maria Manuela Gaspar, Catarina Reis
Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related cancer, and hepatocellular carcinoma. With this focus, we appraised the clinical advantages and drawbacks of metallic, polymeric, and lipid-based nanosystems, such as low invasiveness, low toxicity to the surrounding healthy tissues, high precision, deeper tissue penetration, and dosage adjustment in a real-time setting...
January 8, 2019: Pharmaceutics
Declan G Murphy, Arun A Azad, Shahneen Sandhu, John Violet, Michael S Hofman
No abstract text is available yet for this article.
January 4, 2019: European Urology
Silvano Gnesin, Francesco Cicone, Periklis Mitsakis, Axel Van der Gucht, Sébastien Baechler, Raymond Miralbell, Valentina Garibotto, Thomas Zilli, John O Prior
BACKGROUND: Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. This study presents the first human dosimetry of 68 Ga-NODAGA-MJ9 in the first five consecutive patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol. Five male patients with biochemical relapse of prostate adenocarcinoma underwent four whole-body time-of-flight PET/CT scans within 2 h after tracer injection...
December 12, 2018: EJNMMI Research
Mitesh Patel, Manojkumar Sachidanandan, Mohd Adnan
Serine/arginine protein kinase 1 (SRPK1); a versatile functional moonlighting protein involved in varied cellular activities comprised of cell cycle progression, innate immune response, chromatin reorganization, negative and positive regulation of viral genome replication, protein amino acid phosphorylation, regulation of numerous mRNA-processing pathways, germ cell development as well as inflammation due to acquaintances with many transcription factors and signaling pathways. Several diseases including cancer have been associated with dysregulation of SRPK1...
December 8, 2018: Molecular Biology Reports
Clara Santos-Cuevas, Guillermina Ferro-Flores, Francisco O García-Pérez, Nallely Jiménez-Mancilla, Gerardo Ramírez-Nava, Blanca Ocampo-García, Myrna Luna-Gutiérrez, Erika Azorín-Vega, Jenny Davanzo, Irma Soldevilla-Gallardo
SPECT/CT images in patients have demonstrated the ability of [99m Tc]Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ([99m Tc]Tc-iPSMA) to detect tumors and metastases of prostate cancer. Considering that theranostics combines the potential of therapeutic and diagnostic radionuclides in the same molecular probe, the aim of this research was to estimate the biokinetics and dosimetry of 177 Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu (177 Lu-iPSMA) in healthy subjects and analyze the response in patients receiving 177 Lu-iPSMA therapeutic doses...
2018: Contrast Media & Molecular Imaging
Pirabu Sakthivel, Arun Prashanth, Alok Thakar, Rajeev Kumar, Rakesh Kumar
The prostate-specific membrane antigen (PSMA) is highly expressed in prostatic cancer. However, PSMA expression is also noted in various benign and malignant nonprostatic neoplasms in the endothelial cells of tumor-associated neovasculature. We performed Ga-PSMA PET/CT in a 14-year-old boy with juvenile nasal angiofibroma (JNA) to explore its theranostic potential. The scan revealed high uptake in the lesion. Performance of PSMA PET/CT in JNA opens up new frontiers with respect to radiological staging, early recurrence identification, and perhaps even radioligand therapy of residual/recurrent JNAs in the future...
December 3, 2018: Clinical Nuclear Medicine
Stefano Fanti, Silvia Minozzi, Gerald Antoch, Ian Banks, Alberto Briganti, Ignasi Carrio, Arturo Chiti, Noel Clarke, Matthias Eiber, Johann De Bono, Karim Fizazi, Silke Gillessen, Sam Gledhill, Uwe Haberkorn, Ken Herrmann, Rodney J Hicks, Frederic Lecouvet, Rodolfo Montironi, Piet Ost, Joe M O'Sullivan, Anwar R Padhani, Jack A Schalken, Howard I Scher, Bertrand Tombal, R Jeroen A van Moorselaar, Heindrik Van Poppel, Hebert Alberto Vargas, Jochen Walz, Wolfgang A Weber, Hans-Jürgen Wester, Wim J G Oyen
Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process...
December 2018: Lancet Oncology
Florian C Maier, Anna-Maria Wild, Niklas Kirchen, Felix Holm, Kerstin Fuchs, Johannes Schwenck, Andreas Maurer, Stefan Wiehr
Here, we describe immuno-Cerenkov luminescence imaging (immuno-CLI) with a specific monoclonal antibody-based tracer for the detection of prostate tumors, which is used in preclinical positron emission tomography (PET) imaging. As PET isotopes generate a continuous spectrum of light in the ultraviolet/visible (UV/vis) wavelength range (Cerenkov luminescence, CL) in dielectric materials and consequently inside living tissues, these isotopes can also be detected by luminescence imaging performed with optical imaging (OI) systems...
September 8, 2018: Applied Radiation and Isotopes
Ryo Nakajima, Zora Nováková, Werner Tueckmantel, Lucia Motlová, Cyril Bařinka, Alan P Kozikowski
The design and synthesis of prostate specific membrane antigen (PSMA) ligands derived from 2-aminoadipic acid, a building block that has not previously been used to construct PSMA ligands, are reported. The effects of both the linker length and of an N-substituent of our PSMA ligands were probed, and X-ray structures of five of these ligands bound to PSMA were obtained. Among the ligands disclosed herein, 13b showed the highest inhibitory activity for PSMA. As ligand 13b can readily be radiolabeled since its fluorine atom is adjacent to the nitrogen atom of its pyridine ring, the use of this and related compounds as theranostics can be pursued...
November 8, 2018: ACS Medicinal Chemistry Letters
Louise Emmett, Megan Crumbaker, Bao Ho, Kathy Willowson, Peter Eu, Lalith Ratnayake, Richard Epstein, Ashley Blanksby, Lisa Horvath, Alex Guminski, Kate Mahon, Craig Gedye, Charlotte Yin, Phillip Stricker, Anthony M Joshua
BACKGROUND: 177 Lu-PSMA-617 (Lu-PSMA) is an emerging therapy in men with metastatic castration-resistant prostate cancer. Paired theranostic agents have the potential to visually identify phenotypes that will respond to targeted therapy. This study examined the value of 68 Ga-HBEDD PSMA-11; prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in predicting treatment response and disease progression in Lu-PSMA therapy within the context of a phase 2 prospective pilot trial...
September 27, 2018: Clinical Genitourinary Cancer
Joana Fernandes Guerreiro, Vítor Alves, Antero José Abrunhosa, António Paulo, Octávia Monteiro Gil, Filipa Mendes
64 CuCl₂ has recently been proposed as a promising agent for prostate cancer (PCa) theranostics, based on preclinical studies in cellular and animal models, and on the increasing number of human studies documenting its use for PCa diagnosis. Nevertheless, the use of 64 CuCl₂ raises important radiobiological questions that have yet to be addressed. In this work, using a panel of PCa cell lines in comparison with a non-tumoral prostate cell line, we combined cytogenetic approaches with radiocytotoxicity assays to obtain significant insights into the cellular consequences of exposure to 64 CuCl₂...
November 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Stephen D Kozuch, Christopher N Cultrara, Adah E Beck, Claudia J Heller, Sunil Shah, Mayurbhai R Patel, Jenny Zilberberg, David Sabatino
The integration of therapy and diagnostics, termed "theranostics", has recently gained widespread utility in the development of new and improved therapeutics that effectively diagnose and treat diseases, such as cancer. In this study, the covalent attachment of multiple fluorescent labels (i.e., fluorescein isothiocyanate (FITC)) to a wide range of siRNAs, including those adopting linear, V- and Y-shape nanostructures, was successfully accomplished by solid-phase bioconjugation for monitoring cell uptake, co-localization, and biological activity in cell culture...
October 31, 2018: ACS Omega
Sagnik Sengupta, Mena Asha Krishnan, Premansh Dudhe, Ramesh B Reddy, Bishnubasu Giri, Sudeshna Chattopadhyay, Venkatesh Chelvam
In this article, we have successfully designed and demonstrated a novel continuous process for assembling targeting ligands, peptidic spacers, fluorescent tags and a chelating core for the attachment of cytotoxic molecules, radiotracers, nanomaterials in a standard Fmoc solid-phase peptide synthesis in high yield and purity. The differentially protected Fmoc-Lys-(Tfa)-OH plays a vital role in attaching fluorescent tags while growing the peptide chain in an uninterrupted manner. The methodology is versatile for solid-phase resins that are sensitive to mild and strong acidic conditions when acid-sensitive side chain amino protecting groups such as Trt (chlorotrityl), Mtt (4-methyltrityl), Mmt (4-methoxytrityl) are employed to synthesise the ligand targeted fluorescent tagged bioconjugates...
2018: Beilstein Journal of Organic Chemistry
A S Pitek, H Hu, S Shukla, N F Steinmetz
Nanotechnology holds great promise in cancer drug delivery, and of particular interest are theranostic approaches in which drug delivery and imaging are integrated. In this work, we studied and developed the plant virus tobacco mosaic virus (TMV) as a platform nanotechnology for drug delivery and imaging. Specifically, a serum albumin (SA)-coated TMV formulation was produced. The SA coating fulfils two functions: SA provides a stealth coating for enhanced biocompatibility; it also acts as a targeting ligand enabling efficient tumor accumulation of SA-TMV versus TMV in mouse models of breast and prostate cancer...
November 21, 2018: ACS Applied Materials & Interfaces
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