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Bone Metastases Prostate cancer

Francisco Osvaldo García-Pérez, Jenny Davanzo, Sergio López-Buenrostro, Clara Santos-Cuevas, Guillermina Ferro-Flores, Miguel A Jímenez-Ríos, Anna Scavuzzo, Zael Santana-Ríos, Sevastián Medina-Ornelas
Positron emission tomography (PET) with prostate-specific membrane antigen (PSMA) has found widespread use for the diagnosis of biochemical recurrence of prostate cancer (PCa). Unfortunately, PET/CT is not as widely available; thus a PSMA-targeting compound for scintigraphy is of special interest. The aim of this study was to compare 99m Tc-EDDA/HYNIC-iPSMA and 68 Ga-PSMA-11 PET/CT qualitatively and semi-quantitatively. Twenty-three patients with metastatic PCa were underwent 99m Tc-EDDA/HYNIC-iPSMA SPECT/CT followed by 68 Ga-PSMA-11 PET/CT...
2018: American Journal of Nuclear Medicine and Molecular Imaging
Tobias Lange, Su Jung Oh-Hohenhorst, Simon A Joosse, Klaus Pantel, Oliver Hahn, Tobias Gosau, Sergey A Dyshlovoy, Jasmin Wellbrock, Susanne Feldhaus, Hanna Maar, Renate Gehrcke, Martina Kluth, Ronald Simon, Thorsten Schlomm, Hartwig Huland, Udo Schumacher
Here we describe the establishment and characterization of an AR+, PSMA+, ERG+, PTEN-/- , CHD1+/- patient-derived xenograft (PDX) model termed 'C5', which has been developed from a 60 years old patient suffering from castration-resistant prostate cancer (CRPC). The patient underwent radical prostatectomy, showed early tumor marker PSA recurrence and, one year after surgery, abiraterone resistance. Subcutaneous C5 tumors can be serially transplanted between mice and grow within ~90 days to 1.5-2 cm³ tumors in SCID Balb/c mice (take rate 100%), NOD-scid IL2Rgnull (NSG) mice (100%) and C57BL/6 pfp-/- /rag2-/- mice (66%)...
December 3, 2018: Scientific Reports
Sofiullah Olayinka Abubakar, Yaw Ampem Amoako, Naima Tag, Tessa Kotze
Imaging in prostate cancer is important in defining the local extent of disease, nodal involvement, and identifying metastases. Bone scan is the most commonly used modality for identification of bone metastasis in prostate cancer despite its reported low sensitivity and specificity compared to magnetic resonance imaging (MRI) which is the imaging gold standard for bone metastasis. Gallium-68 prostate-specific membrane antigen positron emission tomography-computed tomography (68 Ga PSMA PET-CT) imaging is a relatively new addition to the imaging modalities in prostate cancer...
October 2018: World Journal of Nuclear Medicine
Manoj Gupta, Partha Sarathi Choudhury, Sudhir Rawal, Harish Chandra Goel, Vineet Talwar, Amitabh Singh, Saroj Kumar Sahoo
Current imaging for prostate cancer (PCa) had limitations for risk stratification and staging. Magnetic resonance imaging frequently underestimated lymph node metastasis while bone scintigraphy often had diagnostic dilemmas. Prostatic-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT) has been remarkable in PCa recurrence. Ninety-seven PSMA PET-CT scans were reanalyzed for tumor node metastases staging and risk stratification of lymph node and distant metastasis proportion...
October 2018: World Journal of Nuclear Medicine
Ajit S Shinto, Madhava B Mallia, Mythili Kameswaran, K K Kamaleshwaran, Jephy Joseph, E R Radhakrishnan, Indira V Upadhyay, R Subramaniam, Madhu Sairam, Sharmila Banerjee, Ashutosh Dash
188 Rhenium-hydroxyethylidene-1,1-diphosphonate (188 Re-HEDP) is a clinically established radiopharmaceutical for bone pain palliation of patients with metastatic bone cancer. Herein, the effectiveness of 188 Re-HEDP for the palliation of painful bone metastases was investigated in an uncontrolled initial trial in 48 patients with different types of advanced cancers. A group of 48 patients with painful bone metastases of lung, prostate, breast, renal, and bladder cancer was treated with 2.96-4.44 GBq of 188 Re-HEDP...
October 2018: World Journal of Nuclear Medicine
Junpei Iizuka
Radium-223 is a first-in-class targeted alpha therapy indicated for treating bone metastases from metastatic castration-resistant prostate cancer (mCRPC) without visceral metastases. Imaging plays an important role in the selection of patients eligible for radium-223 therapy. In the ALSYMPCA trial protocol, bone scintigraphy was used to detect lesions, essentially osteoblastic bone metastases, whereas computed tomography (CT) was used to exclude visceral metastases, with no interim imaging until treatment completion unless clinically indicated...
November 2018: Asia-Pacific Journal of Clinical Oncology
Foon-Yiu Cheung
Bone metastases are a hallmark of advanced prostate cancer and may drive the morbidity and mortality of the disease in patients with a poor prognosis. The pathogenesis of bone metastasis involves the interaction between cancer cells, normal bone cells and the bone microenvironment. Targeting the bone microenvironment has become a promising therapy for patients with advanced prostate cancer and bone metastasis. This article reviews the use of the antiresorptive bone-targeted agents zoledronic acid and denosumab in the management of skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastasis...
November 2018: Asia-Pacific Journal of Clinical Oncology
Emma E van der Toom, Haley D Axelrod, Jean J de la Rosette, Theo M de Reijke, Kenneth J Pienta, Kenneth C Valkenburg
Despite improvements in early detection and advances in treatment, patients with prostate cancer continue to die from their disease. Minimal residual disease after primary definitive treatment can lead to relapse and distant metastases, and increasing evidence suggests that circulating tumour cells (CTCs) and bone marrow-derived disseminated tumour cells (BM-DTCs) can offer clinically relevant biological insights into prostate cancer dissemination and metastasis. Using epithelial markers to accurately detect CTCs and BM-DTCs is associated with difficulties, and prostate-specific markers are needed for the detection of these cells using rare cell assays...
November 27, 2018: Nature Reviews. Urology
Donghui Zhou, Khuchtumur Bum-Erdene, David Xu, Degang Liu, Doug Tompkins, Rania S Sulaiman, Timothy W Corson, John M Chirgwin, Samy O Meroueh
Bone is a common site of metastasis for breast, prostate, lung, kidney and other cancers. Bone metastases are incurable, and substantially reduce patient quality of life. To date, there exists no small-molecule therapeutic agent that can reduce tumor burden in bone. This is partly attributed to the lack of suitable in vitro assays that are good models of tumor growth in bone. Here, we take advantage of a novel ex vivo model of bone colonization to report a series of pyrrolopyrazolone small molecules that inhibit cancer cell invasion and ex vivo tumor growth in bone at single-digit micromolar concentration...
November 16, 2018: Bioorganic & Medicinal Chemistry
Spencer C Behr, Rahul Aggarwal, Henry F Van Brocklin, Robert R Flavell, Kenneth Geo, Eric J Small, Joseph Blecha, Salma Jivan, Thomas A Hope, Jeffrey P Simko, John Kurhanewicz, Susan M Noworolski, Natalie J Korn, Romelyn De Los Santos, Matthew R Cooperberg, Peter R Carroll, Hao G Nguyen, Kirsten L Greene, Beatrice Langton-Webster, Clifford E Berkman, Youngho Seo
Prostate-specific membrane antigen (PSMA) targeting agents comprise a rapidly emerging class of radiopharmaceuticals for prostate cancer diagnostic imaging. Unlike most other PSMA agents with a urea-backbone, CTT1057 is based on a phosphoramidate scaffold that irreversibly binds to PSMA. We conducted a first-in-human Phase I study of CTT1057 in patients with localized and metastatic prostate cancer. Methods: Two patient cohorts were recruited. Cohort A were patients with biopsy-proven localized prostate cancer preceding radical prostatectomy, and cohort B were patients with metastatic castrate resistant prostate cancer...
November 21, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Timothy Perk, Tyler Bradshaw, Song Chen, Hyung-Jun Im, Steve Cho, Scott Perlman, Glenn Liu, Robert Jeraj
PURPOSE: 18 F-NaF PET/CT imaging of bone metastases is confounded by tracer uptake in benign diseases, such as osteoarthritis. The goal of this work was to develop an automated bone lesion classification algorithm to classify lesions in NaF PET/CT images. METHODS: A nuclear medicine physician manually identified and classified 1751 bone lesions in NaF PET/CT images from 37 subjects with metastatic castrate-resistant prostate cancer, 14 of which (598 lesions) were analyzed by three additional physicians...
November 20, 2018: Physics in Medicine and Biology
Jacqui A McGovern, Abbas Shafiee, Ferdinand Wagner, Christoph A Lahr, Marietta Landgraf, Christoph Meinert, Elizabeth D Williams, Pamela J Russell, Judith A Clements, Daniela Loessner, Boris M Holzapfel, Gail P Risbridger, Dietmar W Hutmacher
The primary tumor microenvironment is inherently important in prostate cancer (PCa) initiation, growth and metastasis. However, most current PCa animal models are based on the injection of cancer cells into the blood circulation and bypass the first steps of the metastatic cascade, hence failing to investigate the influence of the primary tumor microenvironment on PCa metastasis. Here, we investigated the spontaneous metastasis of PC3 human PCa cells from humanized prostate tissue, containing cancer-associated fibroblasts (CAFs) and prostate lymphatic and blood vessel endothelial cells (BVEC), to humanized tissue-engineered bone constructs (hTEBC) in NOD-SCID IL2Rγnull (NSG) mice...
November 13, 2018: Cancers
Hala T Borno, Eric J Small
High-risk nonmetastatic castration-resistant prostate cancer is a lethal disease that previously lacked clear treatment options. Progression to bone metastases is associated with significant morbidity and high cost. Apalutamide, an androgen receptor inhibitor, has substantial clinical response in nonmetastatic castration-resistant prostate cancer. Apalutamide + androgen deprivation therapy is well tolerated and improves metastasis-free survival, progression-free survival and time to symptomatic progression, and is associated with a favorable trend of improved overall survival...
November 14, 2018: Future Oncology
Felix Preisser, Elio Mazzone, Sebastiano Nazzani, Michele Marchioni, Marco Bandini, Zhe Tian, Fred Saad, Denis Soulières, Shahrokh F Shariat, Francesco Montorsi, Hartwig Huland, Markus Graefen, Derya Tilki, Pierre I Karakiewicz
BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines provide recommendations for staging of prostate cancer patients in the objective regarding presence of locoregional lymph node metastases (LNM) and bone metastases. We tested the performance characteristics of these recommendations in a community setting. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified patients with available Gleason, clinical stage and prostatic specific antigen...
November 14, 2018: British Journal of Cancer
Akira Joraku, Kentaro Hatano, Koji Kawai, Shuya Kandori, Takahiro Kojima, Nobuyoshi Fukumitsu, Tomonori Isobe, Yutaro Mori, Muneyuki Sakata, Tadashi Hara, Katsuhiro Nasu, Manabu Minami, Yuichi Iizumi, Hiroyuki Nishiyama
OBJECTIVE: We conducted the present phase I/IIa positron emission tomography (PET) imaging study with 89 Zr conjugated with desferroxamine-IAB2M (89 Zr-Df-IAB2M), an anti-prostate-specific membrane-antigen minibody, to assess its safety and feasibility in patients with urological cancer. METHODS: 89 Zr-Df-IAB2M was synthetized by IBA Molecular (Somerset, NJ, USA) and transported by air to Tsukuba Molecular Imaging Center (Tsukuba, Ibaraki, Japan).17 patients received 74 MBq (2 mCi) of 89 Zr-Df-IAB2M at total mass doses of 10 mg...
November 7, 2018: Annals of Nuclear Medicine
Minji Koh, Young Seok Kim, Hanjong Ahn, Choung-Soo Kim
BACKGROUND/AIM: The efficacy of adjuvant or salvage radiation to the regional lymph node area has not been fully investigated in high-risk prostate cancer patients; instead, radiotherapy is limited to the prostate fossa. The present study aimed to assess patterns of recurrence in prostate cancer patients with biochemical failure (BCF) who were treated with whole-pelvic salvage radiotherapy (SRT) following radical prostatectomy. PATIENTS AND METHODS: The clinical data from 196 high-risk prostate cancer patients who received SRT for BCF after radical prostatectomy were reviewed...
November 2018: Anticancer Research
Hendrik Rathke, Paul Flechsig, Walter Mier, Marcus Bronzel, Eleni Mavriopoulou, Manuel Roehrich, Markus Hohenfellner, Frederik L Giesel, Uwe L Haberkorn, Clemens Kratochwil
Due to different physical properties, the beta-emitters 177 Lu and 90 Y offer specific radiation-biological advantages in dedicated clinical situations, respectively. Our objective was to introduce 90 Y-PSMA-617 to clinical application, providing additional avenues for personalized medicine. Here we present our dosimetry-estimate for 90 Y-PSMA-617, report initial clinical experiences and discuss the advantages and drawbacks of varying the beta-emitter in prostate-specific membrane antigen (PSMA) targeting radioligand therapy (RLT)...
November 2, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Atish D Choudhury, Lillian Werner, Edoardo Francini, Xiao X Wei, Gavin Ha, Samuel S Freeman, Justin Rhoades, Sarah C Reed, Gregory Gydush, Denisse Rotem, Christopher Lo, Mary-Ellen Taplin, Lauren C Harshman, Zhenwei Zhang, Edward P O'Connor, Daniel G Stover, Heather A Parsons, Gad Getz, Matthew Meyerson, J Christopher Love, William C Hahn, Viktor A Adalsteinsson
BACKGROUND: Tumor content in circulating cell-free DNA (cfDNA) is a promising biomarker, but longitudinal dynamics of tumor-derived and non-tumor-derived cfDNA through multiple courses of therapy have not been well described. METHODS: CfDNA from 663 plasma samples from 140 patients with castration-resistant prostate cancer (CRPC) was subject to sparse whole genome sequencing. Tumor fraction (TFx) estimated using the computational tool ichorCNA was correlated with clinical features and responses to therapy...
November 2, 2018: JCI Insight
Zohar Keidar, Ronit Gill, Elinor Goshen, Ora Israel, Tima Davidson, Maryna Morgulis, Natalia Pirmisashvili, Simona Ben-Haim
BACKGROUND: 68Ga-PSMA PET/CT has an important role in assessment of prostate cancer patients with biochemical recurrence and is evolving in staging high- and intermediate risk disease. The aim of present study was to describe the metastatic patterns and frequency of involved sites of prostate cancer and to assess the incidence of benign Ga68-PSMA avid PET/CT findings in a large patient population. METHODS: 68Ga-PSMA PET/CT studies performed in two tertiary medical centers over a period of 24 months were retrospectively reviewed...
November 1, 2018: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
Jessica Y Matuoka, James G Kahn, Silvia R Secoli
BACKGROUND: Bone metastases are highly prevalent in breast, prostate, lung and colon cancers. Their symptoms negatively affect quality of life and functionality and optimal management can mitigate these problems. There are two different targeted agents to treat them: bisphosphonates (pamidronate and zoledronic acid) and the monoclonal antibody denosumab. Estimates of cost-effectiveness are still mixed. OBJECTIVE: To conduct a systematic review of economic studies that compares these two options...
October 31, 2018: European Journal of Health Economics: HEPAC: Health Economics in Prevention and Care
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