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Christian Filss, Alexander Heinzel, Berthold Miiller, Andreas T J Vogg, Karl-Josef Langen, Felix M Mottaghy
AIM: In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in177 Lu-PSMA-617 therapy was evaluated. METHODS: Eleven consecutive prostate cancer patients receiving a first cylcle of177 Lu-PSMA-617 (administered activity of approximately 6GBq) were included. The68 Ga-PSMA-11 PET/CT scan previous to therapy was used to determine TTV and SG uptake (glandulae submandibularis) employing PMOD version 3...
February 2018: Nuklearmedizin. Nuclear Medicine
Francesco Ceci, Paolo Castellucci, Stefano Fanti
As precision medicine evolves, the contribution of molecular imaging to the management of prostate cancer (PCa) patients, especially for Positron Emission Tomography (PET) imaging, is gaining importance. Highly successful approaches to measure the expression of the prostate specific membrane antigen (PSMA) have been introduced recently. PSMA, the glutamate carboxypeptidase II (GCP-II), is a membrane bound metallo-peptidase that is overexpressed in 90-100% of PCa cells. Due to its selective over-expression, PSMA is a reliable tissue marker for prostate cancer and is considered an ideal target for tumor specific imaging and therapy...
March 8, 2018: Quarterly Journal of Nuclear Medicine and Molecular Imaging
Ambreen Khawar, Elisabeth Eppard, Jean Phlippe Sinnes, Frank Roesch, Hojjat Ahmadzadehfar, Stefan Kürpig, Michael Meisenheimer, Florian C Gaertner, Markus Essler, Ralph A Bundschuh
AIM: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients. METHODS: Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection...
February 27, 2018: Clinical Nuclear Medicine
Kamran Aryana, Soroush Zarehparvar Moghadam, Roham Salek, Ghasemali Divband
A 76-year-old man with castration-resistant prostate cancer and widespread skeletal metastases underwent 2 cycles of Lu-prostate-specific membrane antigen (PSMA) 617 therapy in our department. Whole-body Lu-PSMA scan after the first cycle showed diffuse skeletal PSMA-avid lesions, whereas no PSMA uptake was evident in the kidneys with minimal PSMA uptake by salivary glands (super scan). After 6 weeks, he received the second dose of Lu-PSMA and whole-body scan after the treatment showed remarkable resolution of skeletal metastases and normal PSMA uptake by the kidneys and salivary glands...
April 2018: Clinical Nuclear Medicine
Martina Benešová, Christoph A Umbricht, Roger Schibli, Cristina Müller
The prostate-specific membrane antigen (PSMA) has emerged as an attractive prostate cancer associated target for radiotheragnostic application using PSMA-specific radioligands. The aim of this study was to design new PSMA ligands modified with an albumin-binding moiety in order to optimize their tissue distribution profile. The compounds were prepared by conjugation of a urea-based PSMA-binding entity, a DOTA chelator, and 4-(p-iodophenyl)butyric acid using multistep solid phase synthesis. The three ligands (PSMA-ALB-02, PSMA-ALB-05, and PSMA-ALB-07) were designed with varying linker entities...
February 5, 2018: Molecular Pharmaceutics
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Markus Hohenfellner, Frederik L Giesel, Uwe Haberkorn, Alfred Morgenstern
The aim of this evaluation is to identify first indicators regarding the efficacy of 225Ac-PSMA-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with 3 cycles of 100 kBq/kgBW 225Ac-PSMA-617 in 2 months intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Prostate-specific membrane antigen (PSMA)-PET/CT or PSMA-SPECT/CT were used for baseline staging and imaging follow-up at month six...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Finn Edler von Eyben, Giandomenico Roviello, Timo Kiljunen, Christian Uprimny, Irene Virgolini, Kalevi Kairemo, Timo Joensuu
AIMS: There is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines...
December 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
Elisabeth Eppard, Ana de la Fuente, Martina Benešová, Ambreen Khawar, Ralph A Bundschuh, Florian C Gärtner, Barbara Kreppel, Klaus Kopka, Markus Essler, Frank Rösch
BACKGROUND: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications...
2017: Theranostics
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
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
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 as68 Ga3+ , and for targeted therapy, such as177 Lu3+ and225 Ac3+ , are substantially different, they may show a preference for macrocycles of different denticity...
December 2017: Nuclear Medicine and Biology
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
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 with177 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 of177 Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle. Patients were followed-up for overall survival (OS)...
January 2018: European Journal of Nuclear Medicine and Molecular Imaging
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
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
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
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-emitter213 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 of68 Ga-PSMA-617. Source organs were kidneys, liver, spleen, salivary glands, bladder, red marrow and representative tumor lesions. The imaging nuclide68 Ga was extrapolated to the half-life of213 Bi...
January 2018: European Journal of Nuclear Medicine and Molecular Imaging
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
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
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
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