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PSMA-617

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https://www.readbyqxmd.com/read/29134280/delayed-response-after-repeated-177-lu-psma-617-radioligand-therapy-in-patients-with-metastatic-castration-resistant-prostate-cancer
#1
Kambiz Rahbar, Martin Bögeman, Anna Yordanova, Maria Eveslage, Michael Schäfers, Markus Essler, Hojjat Ahmadzadehfar
PURPOSE: Radioligand therapy (RLT) using Lutetium-177 labeled PSMA-617 (Lu-PSMA) ligand is a new therapeutic option for salvage therapy in heavily pretreated patients with metastatic castration resistant prostate cancer. The aim of this retrospective study was to analyze response in patients receiving 3 cycles of Lu-PSMA. METHODS: Seventy-one patients (median age: 72 years; range 44-87) received 3 cycles of RLT with Lu-PSMA (mean administered activity: 6.016 ± 0...
November 13, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29097938/labelling-of-90-y-and-177-lu-dota-bioconjugates-for-targeted-radionuclide-therapy-a-comparison-among-manual-semiautomated-and-fully-automated-synthesis
#2
Michele Iori, Pier C Capponi, Sara Rubagotti, Luca Rosario Esposizione, Johanna Seemann, Riccardo Pitzschler, Thorsten Dreger, Debora Formisano, Elisa Grassi, Federica Fioroni, Annibale Versari, Mattia Asti
In spite of the hazard due to the radiation exposure, preparation of (90)Y- and (177)Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of (177)Lu- and (90)Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617) was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both (90)Y- and (177)Lu-labelled radiopharmaceuticals have been performed using the three different methods...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29055836/assessment-of-psma-targeting-ligands-bearing-novel-chelates-with-application-to-theranostics-stability-and-complexation-kinetics-of-68-ga-3-111-in-3-177-lu-3-and-225-ac-3
#3
James M Kelly, Alejandro Amor-Coarasa, Anastasia Nikolopoulou, Dohyun Kim, Clarence Williams, Shankar Vallabhajosula, John W Babich
INTRODUCTION: Recent successes in the treatment of metastatic castration-resistant prostate cancer (mCRPCa) by systemic endoradiotherapy has sparked renewed interest in developing small molecule ligands targeting prostate-specific membrane antigen (PSMA) and chelators capable of stable complexation of metal radionuclides for imaging and therapy. As the size and coordination number of metals for imaging, such as (68)Ga(3+), and for targeted therapy, such as (177)Lu(3+) and (225)Ac(3+), are substantially different, they may show a preference for macrocycles of different denticity...
October 3, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29029496/-177-lu-psma-617-radioligand-therapy-for-a-patient-with-lymph-node-metastatic-prostate-cancer
#4
Finn E von Eyben, Timo Kiljunen, Timo Joensuu, Kalevi Kairemo, Christian Uprimny, Irene Virgolini
Prostate specific membrane antigen (PSMA) is expressed in unfavorable prostate cancer. PSMA is basis for new diagnostics and theranostics. PET/CT using PSMA is more sensitive than choline PET/CT. (177)Lu-PSMA radioligand therapy is mainly used for patients with end-stage prostate cancer. This report describes a patient with a third recurrence in lymph nodes. The recurrence was treated with (177)Lu-PSMA radioligand therapy instead of chemotherapy with docetaxel. The effect was in part evaluated relative to that of two established salvage treatments...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29026946/psma-targeted-radioligandtherapy-in-metastatic-castration-resistant-prostate-cancer-after-chemotherapy-abiraterone-and-or-enzalutamide-a-retrospective-analysis-of-overall-survival
#5
K Rahbar, M Boegemann, A Yordanova, M Eveslage, M Schäfers, M Essler, H Ahmadzadehfar
AIM: Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with (177)Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. METHODS: A total of 104 patients were treated with 351 cycles of (177)Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle...
October 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28974599/molecular-radiotheragnostics-in-prostate-cancer
#6
Yong Du, Sabina Dizdarevic
Two different molecular radio-theragnostic principles are applied in prostate cancer, providing a personalised management for those patients. Firstly, radiopharmaceuticals with the same or similar mechanism of action but different energy (gamma-γ, eg (99m)Tc-diphosphonates or positron-β+, eg 18F-NaF emitting isotopes) can be used to identify patients with osteoblastic metastases for a treatment with bone seeking beta (β-) or alpha (α-) emitting radionuclides to deliver targeted molecular radiotherapy. A number of such β- emitting molecules have been used for bone palliation...
October 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/28924629/a-psma-ligand-labeled-with-cobalt-55-for-pet-imaging-of-prostate-cancer
#7
Johan Hygum Dam, Birgitte Brinkmann Olsen, Christina Baun, Poul Flemming Høilund-Carlsen, Helge Thisgaard
PURPOSE: Prostate-specific membrane antigen (PSMA) comprises a recognized target for molecular imaging of prostate cancer. As such, radiolabeled PSMA inhibitors are of great value for diagnosis and staging of this disease. Herein, we disclose the preclinical characterization of [(55)Co]PSMA-617 for positron emission tomography (PET)/x-ray computed tomography (CT) imaging of prostate cancer lesions. PROCEDURES: By the application of microwave heating, PSMA-617 in acetate buffer (0...
December 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28903443/radioligand-therapy-of-metastatic-prostate-cancer-using-177-lu-psma-617-after-radiation-exposure-to-223-ra-dichloride
#8
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with (177)Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with (223)Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of (177)Lu-PSMA-617 after exposure to more cycles of (223)Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with (223)Ra...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28891033/targeted-alpha-therapy-of-mcrpc-dosimetry-estimate-of-213-bismuth-psma-617
#9
Clemens Kratochwil, Karl Schmidt, Ali Afshar-Oromieh, Frank Bruchertseifer, Hendrik Rathke, Alfred Morgenstern, Uwe Haberkorn, Frederik L Giesel
PURPOSE: PSMA-617 is a small molecule targeting the prostate-specific membrane antigen (PSMA). In this work, we estimate the radiation dosimetry for this ligand labeled with the alpha-emitter (213)Bi. METHODS: Three patients with metastatic prostate cancer underwent PET scans 0.1 h, 1 h, 2 h, 3 h, 4 h and 5 h after injection of (68)Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions...
September 11, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28864607/glu-ureido-based-inhibitors-of-prostate-specific-membrane-antigen-lessons-learned-during-the-development-of-a-novel-class-of-low-molecular-weight-theranostic-radiotracers
#10
REVIEW
Klaus Kopka, Martina Benešová, Cyril Bařinka, Uwe Haberkorn, John Babich
In recent years, several radioligands targeting prostate-specific membrane antigen (PSMA) have been clinically introduced as a new class of theranostic radiopharmaceuticals for the treatment of prostate cancer (PC). In the second decade of the 21(st) century, a new era in nuclear medicine was initiated by the clinical introduction of small-molecule PSMA inhibitor radioligands, 40 y after the clinical introduction of (18)F-FDG. Because of the high incidence and mortality of PC, the new PSMA radioligands have already had a remarkable impact on the clinical management of PC...
September 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28798031/repeated-lu-177-psma-617-radioligand-therapy-using-treatment-activities-up-to-9-3-gbq
#11
Hendrik Rathke, Frederik L Giesel, Paul Flechsig, Klaus Kopka, Walter Mier, Markus Hohenfellner, Uwe Haberkorn, Clemens Kratochwil
Current treatment protocols for (177)Lu-PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness have not yet been proven clinically. We retrospectively report our clinical observations using four different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in PSMA-imaging were treated in fractions of 4 GBq / 80 nmol, 6 GBq / 120 nmol, 7.4 GBq / 150 nmol or 9.3 GBq / 150 nmol (177)Lu-activity / precursor-amount (n = 10, respectively) every 2 months...
August 10, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28719450/combination-of-177lu-psma-617-and-external-radiotherapy-for-the-treatment-of-cerebral-metastases-in-patients-with-castration-resistant-metastatic-prostate-cancer
#12
Xiao Wei, Carl Schlenkhoff, Bettina Schwarz, Markus Essler, Hojjat Ahmadzadehfar
Two castration-resistant prostate cancer patients, both with cerebral and visceral and lymphatic metastases, received multiple cycles of Lu-PSMA-617 treatments. The prognosis of both cases is dependent on brain metastases. Between Lu-PSMA-617 treatment cycles, local radiotherapy was also applied to the brain metastases. Prior to the combined therapy, all systemic metastases, including cerebral lesions, showed PSMA expression using Ga-PSMA PET/CT. Under the combined therapy, all the metastases, particularly the cerebral lesions, showed significant regression in size and PSMA expression over time...
September 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28624848/-177-lu-psma-617-radioligand-therapy-and-outcome-in-patients-with-metastasized-castration-resistant-prostate-cancer
#13
Axel Bräuer, Lena Sophie Grubert, Wolfgang Roll, Andres Jan Schrader, Michael Schäfers, Martin Bögemann, Kambiz Rahbar
PURPOSE: Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with (177)Lu-PSMA-617. METHODS: Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study...
September 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28618401/64cu-psma-617-a-novel-psma-targeted-radio-tracer-for-pet-imaging-in-gastric-adenocarcinoma-xenografted-mice-model
#14
Xue-di Han, Chen Liu, Fei Liu, Qing-Hua Xie, Te-Li Liu, Xiao-Yi Guo, Xiao-Xia Xu, Xing Yang, Hua Zhu, Zhi Yang
Here, we report that it's feasible for imaging gastric adenocarcinoma mice model with prostate-specific membrane antigen (PSMA) targeting imaging agents, which could potentially provide an alternate and readily translational tool for managing gastric adenocarcinoma. DKFZ-PSMA-617, a PSMA targeting ligand reported recently, was chosen to be radio-labeled with nuclide 64Cu. 64Cu-PSMA-617 was radio-synthesized in high radio-chemical yield and specific activity up to 19.3 GBq/μmol. It showed good stability in vitro...
May 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613198/lu-177-psma-617-prostate-specific-membrane-antigen-inhibitor-therapy-in-patients-with-castration-resistant-prostate-cancer-stability-bio-distribution-and-dosimetry
#15
Levent Kabasakal, Türkay Toklu, Nami Yeyin, Emre Demirci, Mohammad Abuqbeitah, Meltem Ocak, Aslan Aygün, Emre Karayel, Hüseyin Pehlivanoğlu, Nalan Alan Selçuk
OBJECTIVE: The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA)-617. METHODS: For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h...
June 1, 2017: Molecular Imaging and Radionuclide Therapy
https://www.readbyqxmd.com/read/28574879/possible-treatment-approach-to-an-extravasation-of-177lu-psma-617
#16
Carl Diedrich Schlenkhoff, Markus Essler, Hojjat Ahmadzadehfar
A rare accident of a subcutaneous extravasation in the elbow with 4280 MBq Lu-PSMA-617 occurred in our clinic. We tried to reduce the damage by warming the elbow for 12 hours, then cooling it, and recommended the patient avoid exercises with the elbow for the next 3 days. We recognized a good resorption of the radionuclide in the scintigraphic imaging in the first 2 days. No pain, burning, or necrosis occurred. The administered therapy afterward showed an adequate decrease in the tumor marker level.
August 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28546332/establishing-177-lu-psma-617-radioligand-therapy-in-a-syngeneic-model-of-murine-prostate-cancer
#17
Wolfgang P Fendler, Andreea D Stuparu, Susan Evans-Axelsson, Katharina Lückerath, Liu Wei, Woosuk Kim, Soumya Poddar, Jonathan Said, Caius G Radu, Matthias Eiber, Johannes Czernin, Roger Slavik, Ken Herrmann
Clinical (177)Lu-PSMA-617 radioligand therapy (RLT) is applied in advanced stage prostate cancer. However, to the best of our knowledge murine models to study the biological effects of various activity levels have not been established. AIM: To optimize specific and total activity for (177)Lu-PSMA-617 RLT in a syngeneic model of murine prostate cancer. Methods: 0.1x106 murine reconstituted, oncogene-driven prostate cancer cells (RM1), transduced to express human prostate-specific membrane antigen (PSMA), were injected into the left flank of C57Bl6 immunocompetent mice...
May 25, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28533936/synthesis-and-evaluation-of-64-cu-psma-617-targeted-for-prostate-specific-membrane-antigen-in-prostate-cancer
#18
Can Cui, Masayuki Hanyu, Akiko Hatori, Yiding Zhang, Lin Xie, Tomoya Ohya, Masami Fukada, Hisashi Suzuki, Kotaro Nagatsu, Cuiping Jiang, Rui Luo, Guoqiang Shao, Mingrong Zhang, Feng Wang
We radiolabeled a ligand, PSMA-617, of prostate-specific membrane antigen (PSMA) with copper-64 ((64)Cu), to evaluate the metabolism, biodistribution, and potential of [(64)Cu]PSMA-617 for PET imaging of prostate cancer. [(64)Cu]PSMA-617 was synthesized by heating PSMA-617 with [(64)Cu]CuCl2 in buffer solution at 90°C for 5 min. In vitro uptake was determined in two cell lines of prostate cancer. In vivo regional distributions were determined in normal and tumor-bearing mice. High radiolabeling efficiency of (64)Cu for PSMA-617 yielded [(64)Cu]PSMA-617 with >99% radiochemical purity...
2017: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28533634/estimation-of-whole-body-radiation-exposure-to-nuclear-medicine-personnel-during-synthesis-of-177-lutetium-labeled-radiopharmaceuticals
#19
Geetanjali Arora, Rajesh Mishra, Praveen Kumar, Madhav Yadav, Sanjana Ballal, Chandrasekhar Bal, Nishikant Avinash Damle
PURPOSE OF THE STUDY: With rapid development in the field of nuclear medicine therapy, radiation safety of the personnel involved in synthesis of radiopharmaceuticals has become imperative. Few studies have been done on estimating the radiation exposure of personnel involved in the radio labeling of (177)Lu-compounds in western countries. However, data from the Indian subcontinent are limited. We have estimated whole body radiation exposure to the radiopharmacist involved in the labeling of: (177)Lu-DOTATATE, (177)Lu-PSMA-617, and (177)Lu-EDTMP...
April 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/28488028/overall-survival-and-response-pattern-of-castration-resistant-metastatic-prostate-cancer-to-multiple-cycles-of-radioligand-therapy-using-177-lu-lu-psma-617
#20
Hojjat Ahmadzadehfar, Simone Wegen, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Xiao Wei, Carl Schlenkhoff, Stefan Hauser, Markus Essler
PURPOSE: Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [(177)Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. METHODS: CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle...
August 2017: European Journal of Nuclear Medicine and Molecular Imaging
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