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PSMA-617

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https://www.readbyqxmd.com/read/28624848/-177-lu-psma-617-radioligand-therapy-and-outcome-in-patients-with-metastasized-castration-resistant-prostate-cancer
#1
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...
June 17, 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
#2
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
#3
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
#4
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.
June 1, 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
#5
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
#6
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
#7
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
#8
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...
May 9, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28474140/comparison-of-psma-hbed-and-psma-i-t-as-diagnostic-agents-in-prostate-carcinoma
#9
Michael McCarthy, Tiffany Langton, Divesh Kumar, Andrew Campbell
PURPOSE: Gallium(68)-labelled prostate-specific membrane antigen (PSMA) radiopharmaceuticals can be used to detect prostate cancer (PCa) cells due the their over expression of PSMA. The (68)Ga HBED-PSMA (PSMA-HBED) ligand has been most widely used and can be considered the current gold standard agent. Further PSMA ligands based on the DOTAGA and DOTA conjugates have more recently been developed. These agents (PSMA-I&T and PSMA-617) have potential theranostic capabilities as they can be conjugated with therapeutic radioisotopes...
May 4, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28427152/radioligand-therapy-of-metastatic-prostate-cancer-using-177lu-psma-617-after-radiation-exposure-to-223ra-dichloride
#10
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with 177Lu-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 223Ra-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 177Lu-PSMA-617 after exposure to more cycles of 223Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with 223Ra...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408529/targeted-alpha-therapy-of-mcrpc-with-225-actinium-psma-617-dosimetry-estimate-and-empirical-dose-finding
#11
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Marcus Bronzel, Christos Apostolidis, Wilko Weichert, Uwe Haberkorn, Frederick Lars Giesel, Alfred Morgenstern
To develop a treatment protocol for (225)Ac-PSMA-617 alpha-radiation therapy in advanced stage, metastatic castration-resistant prostate cancer patients with PSMA-positive tumor phenotype. Methods: A dosimetry estimate was calculated based on time-activity-curves derived from serially performed (177)Lu-PSMA-617 scans extrapolated to the physical half-life of (225)Ac, assuming instant decay of instable daughter nuclides. Salvage therapies empirically conducted with 50kBq/kg (n = 4), 100kBq/kg (n = 4), 150kBq/kg (n = 2), 200kBq/kg (n = 4) (225)Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response...
April 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28337529/the-impact-of-repeated-cycles-of-radioligand-therapy-using-177-lu-lu-psma-617-on-renal-function-in-patients-with-hormone-refractory-metastatic-prostate-cancer
#12
Anna Yordanova, Anja Becker, Elisabeth Eppard, Stefan Kürpig, Christian Fisang, Georg Feldmann, Markus Essler, Hojjat Ahmadzadehfar
BACKGROUND: [(177)Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. METHODS: Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA-617 were investigated...
March 23, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28255795/-213-bi-psma-617-targeted-alpha-radionuclide-therapy-in-metastatic-castration-resistant-prostate-cancer
#13
Mike Sathekge, Otto Knoesen, Marian Meckel, Moshe Modiselle, Mariza Vorster, Sebastian Marx
No abstract text is available yet for this article.
June 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28193503/clinical-translation-of-a-psma-inhibitor-for-99m-tc-based-spect
#14
Guillermina Ferro-Flores, Myrna Luna-Gutiérrez, Blanca Ocampo-García, Clara Santos-Cuevas, Erika Azorín-Vega, Nallely Jiménez-Mancilla, Emmanuel Orocio-Rodríguez, Jenny Davanzo, Francisco O García-Pérez
BACKGROUND: Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. (68)Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare (99m)Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu ((99m)Tc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the (99m)Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer...
February 3, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28102507/-44-sc-psma-617-for-radiotheragnostics-in-tandem-with-177-lu-psma-617-preclinical-investigations-in-comparison-with-68-ga-psma-11-and-68-ga-psma-617
#15
Christoph A Umbricht, Martina Benešová, Raffaella M Schmid, Andreas Türler, Roger Schibli, Nicholas P van der Meulen, Cristina Müller
BACKGROUND: The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging ((68)Ga) and radionuclide therapy ((177)Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced (44)Sc (T 1/2 = 4...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/27922871/excellent-response-to-177lu-psma-617-radioligand-therapy-in-a-patient-with-advanced-metastatic-castration-resistant-prostate-cancer-evaluated-by-68ga-psma-pet-ct
#16
Wolfgang Roll, Axel Bode, Matthias Weckesser, Martin Bögemann, Kambiz Rahbar
Recently radiolabeled ligands targeting prostate specific membrane antigen (PSMA) have been introduced for diagnostics and treatment of prostate cancer. Labeled with Lutetium, PSMA radioligand therapy (RLT) is one of the most promising new treatments of metastatic castration refractory prostate cancer. We present images of Ga-PSMA PET/CT and parameters of response of a 75-year-old heavily pretreated metastatic castration refractory prostate cancer patient with extended bone metastases, showing an extraordinary biochemical response in PSA-levels concordant to SUV decline in bone metastases...
February 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#17
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27789722/preclinical-evaluation-of-18-f-psma-1007-a-new-prostate-specific-membrane-antigen-ligand-for-prostate-cancer-imaging
#18
Jens Cardinale, Martin Schäfer, Martina Benešová, Ulrike Bauder-Wüst, Karin Leotta, Matthias Eder, Oliver C Neels, Uwe Haberkorn, Frederik L Giesel, Klaus Kopka
In recent years, several radiotracers targeting the prostate-specific membrane antigen (PSMA) have been introduced. Some of them have had a high clinical impact on the treatment of patients with prostate cancer. However, the number of (18)F-labeled tracers addressing PSMA is still limited. Therefore, we aimed to develop a radiofluorinated molecule resembling the structure of therapeutic PSMA-617. Methods: The nonradioactive reference compound PSMA-1007 and the precursor were produced by solid-phase chemistry...
March 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27782913/post-therapeutic-dosimetry-of-177lu-dkfz-psma-617-in-the-treatment-of-patients-with-metastatic-castration-resistant-prostate-cancer
#19
Madhav P Yadav, Sanjana Ballal, Madhavi Tripathi, Nishikant A Damle, Ranjit K Sahoo, Amlesh Seth, Chandrasekhar Bal
OBJECTIVE: Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients...
January 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/27765862/german-multicenter-study-investigating-177lu-psma-617-radioligand-therapy-in-advanced-prostate-cancer-patients
#20
MULTICENTER STUDY
Kambiz Rahbar, Hojjat Ahmadzadehfar, Clemens Kratochwil, Uwe Haberkorn, Michael Schäfers, Markus Essler, Richard P Baum, Harshad R Kulkarni, Matthias Schmidt, Alexander Drzezga, Peter Bartenstein, Andreas Pfestroff, Markus Luster, Ulf Lützen, Marlies Marx, Vikas Prasad, Winfried Brenner, Alexander Heinzel, Felix M Mottaghy, Juri Ruf, Philipp Tobias Meyer, Martin Heuschkel, Maria Eveslage, Martin Bögemann, Wolfgang Peter Fendler, Bernd Joachim Krause
(177)Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients. METHODS: One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with (177)Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle...
January 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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