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https://www.readbyqxmd.com/read/29684274/preclinical-development-of-novel-psma-targeting-radioligands-modulation-of-albumin-binding-properties-to-improve-prostate-cancer-therapy
#1
Christoph A Umbricht, Martina Benesova, Roger Schibli, Cristina Müller
The treatment of metastatic castration-resistant prostate cancer (mCRPC) remains challenging with current treatment options. The development of more effective therapies is, therefore, urgently needed. Targeted radionuclide therapy with prostate-specific membrane antigen (PSMA)-targeting ligands has revealed promising clinical results. In an effort to optimize this concept, it was the aim of this study to design and investigate PSMA ligands comprising different types of albumin binders. PSMA-ALB-53 and PSMA-ALB-56 were designed by combining the glutamate-urea PSMA-binding entity, a DOTA chelator and an albumin binder based on the 4-(p-iodophenyl)-moiety or p-(tolyl)-moiety...
April 23, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29680672/targeting-of-folate-conjugated-liposomes-with-co-entrapped-drugs-to-prostate-cancer-cells-via-prostate-specific-membrane-antigen-psma
#2
Yogita Patil, Hilary Shmeeda, Yasmine Amitay, Patricia Ohana, Saran Kumar, Alberto Gabizon
Folate-targeted liposomes (FTL) were tested as drug delivery vehicles to PSMA-positive cancer cells. We used FL with co-entrapped mitomycin C lipophilic prodrug (MLP) and doxorubicin (DOX), and the LNCaP prostate cancer cell line which expresses PSMA but is negative for folate receptor. A major increase in cell drug levels was observed when LNCaP cells were incubated with FTL as compared to non-targeted liposomes (NTL). MLP was activated to mitomycin C, and intracellular and nuclear fluorescence of DOX was detected, indicating FTL processing and drug bioavailability...
April 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29679111/the-impact-of-a-bayesian-penalized-likelihood-reconstruction-algorithm-on-delayed-time-point-ga-68-psma-pet-for-improved-recurrent-prostate-cancer-detection
#3
Tiago Sampaio Vieira, Diogo Borges Faria, Fernando Azevedo Silva, Sérgio Barroso, Graça Fonseca, José Pereira Oliveira
No abstract text is available yet for this article.
April 20, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29678358/impact-of-68-ga-psma-pet-on-the-management-of-patients-with-prostate-cancer-a-systematic-review-and-meta-analysis
#4
REVIEW
Sangwon Han, Sungmin Woo, Yeon Joo Kim, Chong Hyun Suh
CONTEXT: 68 Gallium prostate-specific membrane antigen positron emission tomography (68 Ga-PSMA PET) is an emerging imaging modality for assessment of prostate cancer. Recent studies show promising results regarding its ability to detect recurrent or metastatic prostate cancer superior to that of conventional imaging modalities. However, the impact of 68 Ga-PSMA PET on management of patients with prostate cancer has not been well established. OBJECTIVE: To perform a systematic review and meta-analysis to evaluate the impact of 68 Ga-PSMA PET on management of patients with prostate cancer...
April 17, 2018: European Urology
https://www.readbyqxmd.com/read/29676909/-18-f-positron-emitting-trimethine-cyanine-fluorescent-contrast-for-image-guided-prostate-cancer-management
#5
Harikrishna Kommidi, Hua Guo, Fuad Nurili, Yogindra Vedvyas, Moonsoo M Jin, Timothy D McClure, Behfar Ehdaie, Haluk B Sayman, Oguz Akin, Omer Aras, Richard Ting
[18/19 F]-4, an anionic GCPII/PSMA inhibitor for image-guided intervention in prostate cancer, is described. [19 F]-4 is radiolabeled with a radiochemical yield that is ≥27% and a molar activity of 190 ± 50 mCi/μmol in a <1 h, one-step, aqueous isotopic exchange reaction. [19 F]-4 allows PSMA expression to be imaged by fluorescence (FL) and [18 F]-PET. PC3-PIP (PSMA-positive, EC50 = 6.74 ± 1.33 nM) cancers are specifically delineated in mice that bear 3 million (18 mg) PC3-PIP and PC3 (control, PSMA-negative) cells...
April 20, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29674422/a-perspective-on-the-evolving-story-of-psma-biology-and-psma-based-imaging-and-endoradiotherapeutic-strategies
#6
Denise S O'Keefe, Dean J Bacich, Steve S Huang, Warren D Heston
We will review the evolution of knowledge of the biology of Prostate-Specific Membrane Antigen (PSMA) and how the translation to therapy has also developed. The usual key to discovery is a realistic model for experimentation and hypothesis testing. This is especially true for the prostate where the human prostate differs significantly from that of other often used species for research models. We will emphasize the genetic characterization of PSMA, The nature of the PSMA protein and its role as a carboxypeptidase, with differing important substrates and products in different tissues...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29671080/-lutetium-177-psma-radioligand-therapy-consensus-within-the-framework-of-gkv-funded-care-between-the-university-hospitals-in-aachen-bonn-d%C3%A3-sseldorf-essen-and-cologne-and-the-mdk-nordrhein
#7
REVIEW
H Ahmadzadehfar, P Albers, A Bockisch, M Boegemann, C Böhme, W Burchert, M Dietlein, A Drzezga, U Fabry, G Feldmann, A Heidenreich, A Heinzel, K Herrmann, A Heyll, C Höhling, C Kreuzer, D Laufer, R Mengel, F M Mottaghy, H-W Müller, S C Müller, E Ost, K Rahbar, W Reifenhäuser, M Schäfers, C Schlenkhoff, M Schmidt, I Schmidt-Wolf, C Wildenhain, B Zimmer, M Essler
In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance...
April 18, 2018: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29670866/psma-diagnostics-and-treatments-of-prostate-cancer-become-mature
#8
EDITORIAL
Finn Edler von Eyben, Glenn Stewart Baumann, Richard Paul Baum
No abstract text is available yet for this article.
2018: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29666835/aptamers-and-apple-pies-a-mini-review-of-psma-aptamers-and-lessons-from-donald-s-coffey
#9
REVIEW
Shawn E Lupold
This mini-review article is part of a special issue dedicated to Donald S. Coffey, a pioneer translational research scientist, exemplary mentor, and leader in urologic and urologic oncology research. This article first briefly reflects on life and scientific lessons from Don Coffey. It then reviews the development of two prostate cancer targeting RNA aptamers, xPSM-A9 and xPSM-A10, through in vitro selection for aptamers that bind to the extracellular domain of the Prostate Specific Membrane Antigen (PSMA)...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29664244/the-role-of-68ga-psma-pet-ct-scan-in-biochemical-recurrence-after-primary-treatment-for-prostate-cancer-a-systematic-review-of-literature
#10
Ahmed Eissa, Ahmed El Sherbiny, Rafael F Coelho, Jens Rassweiler, John W Davis, Francesco Porpiglia, Vipul R Patel, Napoleone Prandini, Salvatore Micali, Maria C Sighinolfi, Stefano Puliatti, Bernardo Rocco, Giampaolo Bianchi
INTRODUCTION: Recurrence after primary treatment of prostate cancer is one of the major challenges facing urologists. Biochemical recurrence is not rare and occurs in up to one third of the patients undergoing radical prostatectomy. Management of biochemical recurrence is tailored according to the site and the burden of recurrence. Therefore, developing an imaging technique to early detect recurrent lesions represents an urgent need. Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality that seems to be a promising tool with capability to localize recurrent prostate cancer...
April 17, 2018: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29664103/microfluidic-68-ga-labeling-a-proof-of-principle-study
#11
Sarah Pfaff, Cecile Philippe, Verena Pichler, Marcus Hacker, Markus Mitterhauser, Wolfgang Wadsak
Positron emission tomography (PET) as a tool for molecular imaging of cancer has gained huge interest in the last few years. Gallium-68 is a popular PET nuclide due to its favorable characteristics, like advantageous half-life (68 min) and independency of a cyclotron on-site for its production. Accordingly, several 68Ga-complexes for cancer imaging via PET have been made available during the last few years. In this work, 68Ga-labeled compounds were synthesized applying a commercially available microfluidic device for the first time...
April 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29663686/-68-ga-psma-pet-ct-staging-prior-to-definitive-radiation-treatment-for-prostate-cancer
#12
George Hruby, Thomas Eade, Louise Emmett, Bao Ho, Ed Hsiao, Geoff Schembri, Linxin Guo, Carolyn Kwong, Julia Hunter, Keelan Byrne, Andrew Kneebone
AIM: To explore the utility of prostate specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer. METHODS: All men undergoing PSMA-PET/CT prior to definitive EBRT for intermediate and high-risk prostate cancer were included in our ethics approved prospective database. For each patient, clinical and pathological results, in addition to scan results including site of PSMA positive disease and number of lesions, were recorded...
April 16, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29659395/loss-of-psma-expression-in-non-neuroendocrine-dedifferentiated-acinar-prostate-cancer
#13
Peter Bronsert, Kathrin Reichel, Juri Ruf
The introduction of tracers targeting the prostate-specific membrane antigen (PSMA) has revolutionized PET imaging of acinar prostate adenocarcinoma. In general, an increasing PSMA expression is assumed with increasing dedifferentiation. Whereas loss of PSMA expression has been reported in case of neuroendocrine dedifferentiation, we present a patient with acinar prostate adenocarcinoma with a loss of PSMA expression after chemotherapy on PET/CT and in histological and immunohistochemical analyses. All tissue samples indicated the retention of acinar features but no expression of neuroendocrine markers (NSE, synaptophysin, chromogranin, and CD56), corresponding to nonelevated serum NSE...
April 13, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29659383/prostate-specific-membrane-antigen-negative-metastases-a-potential-pitfall-in-prostate-specific-membrane-antigen-pet
#14
Benjamin Noto, Katharina Auf der Springe, Sebastian Huss, Thomas Allkemper, Lars Stegger
Ga-PSMA-11 PET/CT was performed in a 74-year-old man because of biochemical recurrence of prostate cancer following radiation therapy of the prostate gland 24 months earlier. Besides focal nuclide accumulation in the prostate gland suggestive of local recurrence, PET scan revealed no further pathologic uptake. However, CT showed multiple pulmonic nodules suggestive of metastases. Thoracotomy and pathologic examination revealed the nodules to be prostate cancer metastasis. Furthermore, immunohistochemical staining with PSMA antibodies demonstrated a virtual lack of PSMA expression...
April 13, 2018: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/29655611/development-of-a-ga-68-labeled-pet-tracer-with-short-linker-for-prostate-specific-membrane-antigen-psma-targeting
#15
Sung-Hyun Moon, Mee Kyung Hong, Young Ju Kim, Yun-Sang Lee, Dong Soo Lee, June-Key Chung, Jae Min Jeong
Glu-Urea-Lys (GUL) derivatives have been reported as prostate-specific membrane antigen (PSMA) agent. We developed derivatives of GUL conjugated with NOTA or DOTA via a thiourea linker and tested their feasibility as PSMA imaging agents after labeling with 68 Ga. NOTA-GUL and DOTA-GUL were synthesized and labeled with 68 Ga using generator-eluted 68 GaCl3 in 0.1 M HCl in the presence of 1 M NaOAc at pH 5.5. The stabilities of 68 Ga-labeled compounds in human serum were tested at 37.5 °C. A competitive binding assay was performed using the PSMA-positive prostate cancer cell line 22Rv1 and [125 I]MIP-1072 (PSMA-specific binding agent) as a tracer...
April 5, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29651569/external-radiation-exposure-excretion-and-effective-half-life-in-177-lu-psma-targeted-therapies
#16
J Kurth, B J Krause, S M Schwarzenböck, L Stegger, M Schäfers, K Rahbar
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177 Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177 Lu-PSMA-617 (mean administered activity 6...
April 12, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29651565/synthesis-and-preclinical-evaluation-of-novel-18-f-labeled-glu-urea-glu-based-psma-inhibitors-for-prostate-cancer-imaging-a-comparison-with-18-f-dcfpyl-and-18-f-psma-1007
#17
Stephanie Robu, Alexander Schmidt, Matthias Eiber, Margret Schottelius, Thomas Günther, Behrooz Hooshyar Yousefi, Markus Schwaiger, Hans-Jürgen Wester
BACKGROUND: Due to its high and consistent expression in prostate cancer (PCa), the prostate-specific membrane antigen (PSMA) represents an ideal target for molecular imaging and targeted therapy using highly specific radiolabeled PSMA ligands. To address the continuously growing clinical demand for 18 F-labeled PSMA-probes, we developed two novel Glu-urea-Glu-(EuE)-based inhibitors, EuE-k-18 F-FBOA (1) and EuE-k-β-a-18 F-FPyl (2), both with optimized linker structure and different 18 F-labeled aromatic moieties...
April 12, 2018: EJNMMI Research
https://www.readbyqxmd.com/read/29650029/the-dose-distribution-in-dominant-intraprostatic-tumour-lesions-defined-by-multiparametric-mri-and-psma-pet-ct-correlates-with-the-outcome-in-patients-treated-with-primary-radiation-therapy-for-prostate-cancer
#18
Constantinos Zamboglou, Christina Marie Klein, Benedikt Thomann, Thomas Franz Fassbender, Hans C Rischke, Simon Kirste, Karl Henne, Natalja Volegova-Neher, Michael Bock, Mathias Langer, Philipp T Meyer, Dimos Baltas, Anca L Grosu
No abstract text is available yet for this article.
April 12, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29643670/role-of-early-dynamic-positron-emission-tomography-computed-tomography-with-68ga-prostate-specific-membrane-antigen-hbed-cc-in-patients-with-adenocarcinoma-prostate-initial-results
#19
Gazala Perveen, Geetanjali Arora, Nishikant Avinash Damle, Meghana Prabhu, Saurabh Arora, Madhavi Tripathi, Chandrasekhar Bal, Praveen Kumar, Rajeev Kumar, Prabhjot Singh
Rationale: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is widely used for imaging of prostate cancer (PC) nowadays. However, appearance of bladder activity many a times hampers lesion detection vis-a-vis primary as well as regional nodes. We aimed to assess if early dynamic PET/CT can be a potential solution to this issue. Methodology: A total of 15 biopsy-proven PC patients who were referred to our department for 68 Ga-PSMA PET/CT for staging/restaging were prospectively studied...
April 2018: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/29629912/technical-pitfall-in-68ga-prostate-specific-membrane-antigen-imaging-altered-biodistribution-caused-by-free-68ga-citrate-due-to-radiolysis-showing-increased-vascular-activity
#20
Nir Hod, Reut Anconina, Daniel Levin, Dina Ezroh Kazap, Sophie Lantsberg
As with any new molecular imaging modality, accurate characterization of abnormalities on Ga-PSMA PET/CT imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants, and potential sources of false imaging findings. Altered biodistribution can have a significant impact on scan interpretation. Presented here is a rare case in which radiopharmaceutical radiolysis occurred causing excessive free Ga-citrate showing as an increased vascular activity. As Ga-PSMA PET/CT imaging is a relatively new imaging technique, it is important to be aware of such a potential technical pitfall in clinical practice in order to prevent scan misinterpretation...
April 6, 2018: Clinical Nuclear Medicine
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