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Theranostic prostate

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...
August 14, 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 6, 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...
July 27, 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...
June 22, 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
Peter Kletting, Anne Thieme, Nina Eberhardt, Andreas Rinscheid, Calogero D'Alessandria, Jakob Allmann, Hans-Jürgen Wester, Robert Tauber, Ambros J Beer, Gerhard Glatting, Matthias Eiber
The aim of this work was to develop a theranostic method that allows predicting PSMA-positive tumor volume after radioligand therapy (RLT) based on a pre-therapeutic PET/CT measurement and physiologically based pharmacokinetic/dynamic (PBPK/PD) modeling at the example of RLT using 177 Lu-labeled PSMA for imaging and therapy (PSMA I&T). Methods: A recently developed PBPK model for 177 Lu PSMA I&T RLT was extended to account for tumor (exponential) growth and reduction due to irradiation (linear quadratic model)...
May 10, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Ksenia Lisova, Maxim Sergeev, Susan Evans-Axelsson, Andreea D Stuparu, Seval Beykan, Jeffrey Collins, Jason Jones, Michael Lassmann, Ken Herrmann, David Perrin, Jason T Lee, Roger Slavik, R Michael van Dam
BACKGROUND: Peptides labeled with positron-emitting isotopes are emerging as a versatile class of compounds for the development of highly specific, targeted imaging agents for diagnostic imaging via positron-emission tomography (PET) and for precision medicine via theranostic applications. Despite the success of peptides labeled with gallium-68 (for imaging) or lutetium-177 (for therapy) in the clinical management of patients with neuroendocrine tumors or prostate cancer, there are significant advantages of using fluorine-18 for imaging...
June 2018: Nuclear Medicine and Biology
Vincenzo Cuccurullo, Giuseppe Danilo Di Stasio, Luigi Mansi
Natural history of prostate cancer (PCa) is extremely variable, as it ranges from indolent and slow growing tumors to highly aggressive histotypes. Genetic background and environmental factors co-operate to the genesis and clinical manifestation of the tumor and include among the others race, family, specific gene variants (i.e., BRCA1 and BRCA2 mutations), acute and chronic inflammation, infections, diet and drugs. In this scenario, remaining actual the clinical interest of bone scan (BS) in detecting skeletal metastases, an important role in diagnostic imaging may be also carried out by, positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MRI), which combine morphological information provided by CT and MRI with functional and metabolic data provided by PET acquisitions...
April 2018: World Journal of Nuclear Medicine
Dharmender Malik, Rajender Kumar, Bhagwant Rai Mittal, Harmandeep Singh, Anish Bhattacharya, Shrawan Kumar Singh
PET/CT with Ga-labeled prostate-specific membrane antigen (PSMA) is increasingly recognized as the best imaging modality for disease staging and detection of recurrent prostate cancer. Despite its name, PSMA expression has been reported in a number of nonprostatic benign and malignant pathologies. Apparently, angioneogenesis is the mechanism attributed to increased Ga-PSMA uptake at these sites. Here we illustrate the utility of Ga-PSMA in 5 nonprostatic malignancies that could open up new possibilities for diagnostics and theranostic concepts with PSMA labeled radioligands in nonprostate tumor entities...
July 2018: Clinical Nuclear Medicine
Xiaodong Qin, Lei Fang, Jian Zhao, Shaohua Gou
It is difficult to diagnose and treat castration-resistant prostate cancer (CRPC) which occurs due to the overexpression of androgen receptor (AR). Because there is a high level of AR in CRPC, we designed and prepared three Pt(IV)-based prodrugs targeting AR. Among them, compound 3, a three-in-one hybrid (an AR binding ligand, a cisplatin unit, and a coumarin moiety), was found to display satisfactory AR binding affinity and antagonist activity against androgen receptor, which could also be effectively internalized and visualized in LNCaP (AR+) cells...
May 7, 2018: Inorganic Chemistry
Emmanouil Lymperis, Aikaterini Kaloudi, Werner Sallegger, Ingrid L Bakker, Eric P Krenning, Marion de Jong, Theodosia Maina, Berthold A Nock
Recent advances in oncology involve the use of diagnostic/therapeutic radionuclide-carrier pairs that target cancer cells, offering exciting opportunities for personalized patient treatment. Theranostic gastrin-releasing peptide receptor (GRPR)-directed radiopeptides have been proposed for the management of GRPR-expressing prostate and breast cancers. We have recently introduced the PET tracer 68 Ga-SB3 (SB3, DOTA- p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), a receptor-radioantagonist that enables the visualization of GRPR-positive lesions in humans...
May 16, 2018: Bioconjugate Chemistry
Katharina Lückerath, Andreea D Stuparu, Liu Wei, Woosuk Kim, Caius G Radu, Christine E Mona, Jeremie Calais, Matthew Rettig, Robert E Reiter, Johannes Czernin, Roger Slavik, Ken Herrmann, Matthias Eiber, Wolfgang Fendler
Aim: To improve prostate specific membrane antigen (PSMA) targeted theranostic approaches, robust murine models of prostate cancer are needed. However, important characteristics of preclinical PSMA imaging, i.e. reproducibility of the imaging signal and the relationship between quantitative cell surface PSMA expression and lesion detectability with microPET/CT, have not been defined yet. Methods: Murine prostate cancer RM1 sublines expressing varying levels of human PSMA were injected into the shoulder of C57Bl/6 mice on day 0...
March 30, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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