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Theranostic prostate

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
Katharina Lückerath, Liu Wei, Wolfgang P Fendler, Susan Evans-Axelsson, Andreea D Stuparu, Roger Slavik, Christine E Mona, Jeremie Calais, Matthew Rettig, Robert E Reiter, Ken Herrmann, Caius G Radu, Johannes Czernin, Matthias Eiber
BACKGROUND: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a promising yet not curative approach in castration-resistant (CR) prostate cancer (PC). Rational combination therapies may improve treatment efficacy. Here, we explored the effect of androgen receptor blockade (ARB) on PSMA expression visualized by PET and its potential additive effect when combined with 177 Lu-PSMA RLT in a mouse model of prostate cancer. METHODS: Mice bearing human CRPC (C4-2 cells) xenografts were treated with 10 mg/kg enzalutamide (ENZ), with 50 mg/kg bicalutamide (BIC), or vehicle (control) for 21 days...
October 29, 2018: EJNMMI Research
R S Eapen, T C Nzenza, D G Murphy, M S Hofman, M Cooperberg, N Lawrentschuk
The heterogeneity of prostate cancer has made imaging modalities of crucial importance in this disease. Accurate diagnosis and staging of the volume and extent of disease, especially in advanced and metastatic prostate cancer, can help to tailor the timing and modalities of treatment. While MRI has been effective in the detection of significant prostate cancer, its use in the identification and quantification of extraprostatic disease is limited. This gap is now being filled by PSMA PET. PSMA PET scans have now been shown to have a role in all stages in the prostate cancer journey...
October 29, 2018: World Journal of Urology
Tang Gao, Anyao Bi, Shuiqi Yang, Yi Liu, Xiangqi Kong, Wenbin Zeng
Prostate cancer (PCa) is the most common type of cancer in men with high morbidity and mortality. However, the current treatment with drugs often leads to chemotherapy resistance. It is known that the multi-disciplines research on molecular imaging is very helpful for early diagnosing, staging, restaging and precise treatment of PCa. In the past decades, the tumor-specific targeted drugs were developed for the clinic to treat prostate cancer. Among them, the emerging nanotechnology has brought about many exciting novel diagnosis and treatments systems for PCa...
2018: Advances in Experimental Medicine and Biology
Souad Adriouach, Vassily Vorobiev, Gregor Trefalt, Eric Allémann, Norbert Lange, Andrej Babič
Novel nanoscale drug delivery biomaterials are of great importance for the diagnosis and treatment of different cancers. We have developed a new pegylated squalene (SQ-PEG) derivative with self-assembly properties. Supramolecular assembly with a lipophilic photosensitizer pyropheophorbide-a (Ppa) by nanoprecipitation gave nanoconstructs SQ-PEG:Ppa with an average size of 200 nm in diameter and a drug loading of 18% (w/w). The composite material demonstrates nanoscale optical properties by tight packing of Ppa within Sq-PEG:Ppa resulting in 99...
October 7, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Joseph M Keca, Michael S Valic, Miffy H Y Cheng, Wenlei Jiang, Marta Overchuk, Juan Chen, Gang Zheng
The discovery and synthesis of multifunctional organic building blocks for nanoparticles have remained challenging. Texaphyrin macrocycles are multifunctional, all-organic compounds that possess versatile metal-chelation capabilities and unique theranostics properties for biomedical applications. Unfortunately, there are significant difficulties associated with the synthesis of texaphyrin-based subunits capable of forming nanoparticles. Herein, the detailed synthesis of a texaphyrin-phospholipid building block is reported via a key 1,2-dinitrophenyl-phospholipid intermediate, along with stable chelation of two clinically relevant metal ions into texaphyrin-lipid without compromising their self-assembly into texaphyrin nanoparticles or nanotexaphyrin...
September 13, 2018: Advanced Healthcare Materials
Tomáš David, Veronika Hlinová, Vojtěch Kubíček, Ralf Bergmann, Franziska Striese, Nicole Berndt, Dávid Szöllősi, Tibor Kovács, Domokos Máthé, Michael Bachmann, Hans-Jürgen Pietzsch, Petr Hermann
Bifunctional derivatives of bis(phosphinate)-bearing cyclam (BPC) chelators bearing a carboxylate, amine, isothiocyanate, azide, or cyclooctyne in the BP side chain were synthesized. Conjugations required no protection of phosphinate or ring secondary amine groups. The ring amines were not reactive (proton protected) at pH < ∼8. For isothiocyanate coupling, oligopeptide N-terminal α-amines were more suitable than alkyl amines, e.g., Lys ω-amine (p Ka ∼7.5-8.5 and ∼10-11, respectively) due to lower basicity...
September 24, 2018: Journal of Medicinal Chemistry
Rahul Vithalrao Parghane, Sandip Basu
Transformed small cell carcinoma of prostate represents a distinct tumor biology from the adenocarcinoma counterpart and penile metastasis from prostate cancer is a rare entity. Unique features of this transformation include unresponsiveness to hormonal therapy and presence of visceral metastases, which can demonstrate hypermetabolism on 18 F-FDG PET/CT. The importance of dual tracer PET/CT using 68 Ga-PSMA and 18 F-FDG is illustrated in metastatic prostatic adenocarcinoma (Gleason's score 4+3=7) with previous history of bilateral orchidectomy, chemotherapy and radiotherapy, who presented with abdominal pain and backache, dysuria and increasing serum PSA...
August 23, 2018: Journal of Nuclear Medicine Technology
Martina Wirtz, Alexander Schmidt, Margret Schottelius, Stephanie Robu, Thomas Günther, Markus Schwaiger, Hans-Jürgen Wester
BACKGROUND: Several radiolabeled prostate-specific membrane antigen (PSMA) inhibitors based on the lysine-urea-glutamate (KuE) motif as the pharmacophore proved to be suitable tools for PET/SPECT imaging of the PSMA expression in prostate cancer patients. PSMA I&T, a theranostic tracer developed in our group, was optimized through alteration of the peptidic structure in order to increase the affinity to PSMA and internalization in PSMA-expressing tumor cells. However, further structural modifications held promise to improve the pharmacokinetic profile...
August 22, 2018: EJNMMI Research
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