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Theranostic prostate

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 200nm 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
Simona Malaspina, Ugo De Giorgi, Jukka Kemppainen, Angelo Del Sole, Giovanni Paganelli
Positron emission tomography (PET) has been commonly and successfully used, in combination with computed tomography (CT) and more recently magnetic resonance (MRI), in the workup of intermediate or high-risk prostate cancer (PCa). Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging have been introduced; one of the most used is 68 Ga-PSMA, that evaluates the expression of prostate-specific membrane antigen (PSMA). This tracer has been rapidly taken into account for its better sensitivity and specificity compared to lipid metabolism tracers, such as 11 C/18 F labelled fluorocholine...
August 16, 2018: La Radiologia Medica
Rudolf A Werner, Ralph A Bundschuh, Lena Bundschuh, Mehrbod S Javadi, Takahiro Higuchi, Alexander Weich, Sara Sheikhbahaei, Kenneth J Pienta, Andreas K Buck, Martin G Pomper, Michael A Gorin, Constantin Lapa, Steven P Rowe
Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET)-based imaging agents for prostate carcinoma and neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers...
October 2018: Annals of Nuclear Medicine
Alexander Schmidt, Martina Wirtz, Stefanie Felicitas Färber, Theresa Osl, Roswitha Beck, Margret Schottelius, Markus Schwaiger, Hans-Jürgen Wester
To investigate the effect of carbohydrate moieties on the pharmacokinetic profile of prostate-specific membrane antigen (PSMA) inhibitors, carbohydrated derivatives of the established PSMA-targeted radiopharmaceutical PSMA I&T were developed and evaluated. As observed for the reference PSMA I&T, the nat Ga/nat Lu complexes of the respective galactose-, mannose-, and cellobiose-conjugated analogs showed high PSMA affinity. Carbohydration had almost no effect on the lipophilicity, whereas PSMA-mediated internalization was reduced...
July 31, 2018: ACS Omega
Yuanyuan Qiu, Yuqing Zhang, Mingwang Li, Gaoxian Chen, Chenchen Fan, Kai Cui, Jian-Bo Wan, Anpan Han, Jian Ye, Zeyu Xiao
The inability to intraoperatively diagnose and eliminate microscopic residual tumors represents a significant challenge in cancer surgery. These residual microtumors cause lethal recurrence and metastasis. Herein, we show a crucial example of Raman imaging with gap-enhanced Raman tags (GERTs) to serve as a robust platform for intraoperative detection and eradication of residual microscopic foci, which exist in surgical margins, tumor invasion, and multifocal tumor spread. The GERTs feature gap-enhanced gold core-shell nanostructures, with Raman reporters embedding inside the interior gap junction...
August 28, 2018: ACS Nano
Lutske Lodewijk, Stefan M Willems, Koen M A Dreijerink, Bart de Keizer, Paul J van Diest, Abbey Schepers, Hans Morreau, Han J Bonenkamp, Ilse A C H Van Engen-van Grunsven, Schelto Kruijff, Bettien M van Hemel, Thera P Links, Els Nieveen van Dijkum, Susanne van Eeden, Gerlof D Valk, Inne H M Borel Rinkes, Menno R Vriens
No abstract text is available yet for this article.
July 25, 2018: Human Pathology
Alexander Wurzer, Julia Pollmann, Alexander Schmidt, Dominik Reich, Hans-Jürgen Wester, Johannes Notni
Radiopharmaceuticals targeting the enzyme prostate-specific membrane antigen (PSMA; synonyms: glutamate carboxypeptidase II, NAALADase; EC have recently emerged as powerful agents for diagnosis and therapy (theranostics) of prostate carcinoma (PCa). The radiation doses for therapeutic application of such compounds are limited by substantial uptakes in kidneys and salivary glands, with excess doses reportedly leading to radiotoxicity-related adverse effects, such as kidney insufficiency or xenostomia...
September 4, 2018: Molecular Pharmaceutics
Saurabh Arora, Meghana Prabhu, Nishikant Avinash Damle, Chandrasekhar Bal, Praveen Kumar, Harish Nalla, Sreedharan Thankarajan Arun Raj
Prostate-specific membrane antigen (PSMA) expression has been shown in neovasculature of various malignancies. Recurrent medullary thyroid cancer (MTC) is difficult to treat. We present the findings on PSMA-positron emission tomography/computed tomography (PET/CT) of a 68-year-old man with MTC, who presented with a recurrent left paratracheal mass and rising calcitonin. The scan revealed significant uptake on PSMA imaging but not on 68 Ga-DOTANOC PET/CT. 177 Lu-PRRT is one of the therapeutic options in patients with recurrent MTC, but in this case was not possible due to lack of somatostatin receptor expression...
July 2018: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
Frédéric Arsenault, Jean-Mathieu Beauregard, Frédéric Pouliot
PURPOSE OF REVIEW: In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i...
September 2018: Current Opinion in Supportive and Palliative Care
Carolina Garri, Shannon Howell, Katrin Tiemann, Aleczandria Tiffany, Farzad Jalali-Yazdi, Mario M Alba, Jonathan E Katz, Terry T Takahashi, Ralf Landgraf, Mitchell E Gross, Richard W Roberts, Kian Kani
The cancer-associated protein Anterior Gradient 2 (AGR2) has been described, predominantly in adenocarcinomas. Increased levels of extracellular AGR2 (eAGR2) have been correlated with poor prognosis in cancer patients, making it a potential biomarker. Additionally, neutralizing AGR2 antibodies showed preclinical effectiveness in murine cancer models suggesting eAGR2 may be a therapeutic target. We set out to identify a peptide by mRNA display that would serve as a theranostic tool targeting AGR2. This method enables the selection of peptides from a complex (>1011 ) library and incorporates a protease incubation step that filters the selection for serum stable peptides...
June 8, 2018: Oncotarget
Nilantha Bandara, Tamila J Stott Reynolds, Rebecca Schehr, Rajendra P Bandari, Philipp J Diebolder, Stephanie Krieger, Jingli Xu, Yubin Miao, Buck E Rogers, Charles J Smith
INTRODUCTION: In this study, we describe development of a true matched-pair theranostic agent that is able to target the αV β3 integrin and the gastrin releasing peptide receptor (GRPR). We herein describe methods to metallate and characterize the new conjugate and to validate its biological efficacy by in vitro and in vivo methods. METHODS: We have previously described the development of [RGD-Glu-6Ahx-RM2] (where RGD: Arg-Gly-Asp; Glu: glutamic acid; 6-Ahx: 6-amino hexanoic acid; RM2: (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2)) that has been conjugated to a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) bifunctional chelating agent (BFCA) to afford [RGD-Glu-[DO3A]-6-Ahx-RM2] peptide...
July 2018: Nuclear Medicine and Biology
Kambiz Rahbar, Ali Afshar-Oromieh, Hossein Jadvar, Hojjat Ahmadzadehfar
Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177 Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT...
January 2018: Molecular Imaging
Andreas G Wibmer, Hedvig Hricak, Gary A Ulaner, Wolfgang Weber
Hybrid imaging plays a central role in the diagnosis and management of a wide range of malignancies at all stages. In this article, we review the most pertinent historical developments, emerging clinical applications of novel radiotracers and imaging technologies, and potential implications for training and practice. This includes an overview of novel tracers for prostate, breast, and neuroendocrine tumors, assessment of tumor heterogeneity, the concept of image-guided 'biologically relevant dosing', and theranostic applications...
2018: European journal of hybrid imaging
Till Wüstemann, Uwe Haberkorn, John Babich, Walter Mier
The high incidence rates of prostate cancer (PCa) raise demand for improved therapeutic strategies. Prostate tumors specifically express the prostate-specific membrane antigen (PSMA), a membrane-bound protease. As PSMA is highly overexpressed on malignant prostate tumor cells and as its expression rate correlates with the aggressiveness of the disease, this tumor-associated biomarker provides the possibility to develop new strategies for diagnostics and therapy of PCa. Major advances have been made in PSMA targeting, ranging from immunotherapeutic approaches to therapeutic small molecules...
May 17, 2018: Medicinal Research Reviews
Harshad R Kulkarni, Aviral Singh, Thomas Langbein, Christiane Schuchardt, Dirk Mueller, Jingjing Zhang, Coline Lehmann, Richard P Baum
Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate-specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabeled PSMA ligands. These small molecules binding the PSMA can be radiolabeled with γ-emitters like 99m Tc and 111 In or positron emitters like 68 Ga and 18 F for diagnosis as well as with their theranostic pairs such as 177 Lu (β-emitter) or 225 Ac (α-emitter) for therapy...
June 1, 2018: British Journal of Radiology
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