1,768 results on '"Czernin, Johannes"'
Search Results
52. Efficacy and toxicity of [177Lu]Lu-PSMA-617 for metastatic castration-resistant prostate cancer in a real-world setting: Results from the U.S. Expanded Access Program and comparisons with phase 3 VISION data.
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Calais, Jeremie, primary, Murthy, Vishnu, additional, Voter, Andrew, additional, Nguyen, Kathleen, additional, Allen-Auerbach, Martin S., additional, Caputo, Sydney, additional, Ledet, Elisa M., additional, Akerele, Opeoluwa, additional, Moradi Tuchayi, Abuzar, additional, Lawhn Heath, Courtney, additional, Carducci, Michael Anthony, additional, Pomper, Martin, additional, Paller, Channing Judith, additional, Czernin, Johannes, additional, Solnes, Lilja, additional, Hope, Thomas A., additional, Sartor, Oliver, additional, and Gafita, Andrei, additional
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- 2024
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53. Prostate-specific membrane antigen PET/CT-guided, metastasis-directed radiotherapy for oligometastatic castration-resistant prostate cancer.
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Nikitas, John, primary, Castellanos, Angela, additional, Farolfi, Andrea, additional, Seyedroudbari, Ameen, additional, Kishan, Amar Upadhyaya, additional, Nickols, Nicholas George, additional, Steinberg, Michael L., additional, Czernin, Johannes, additional, and Calais, Jeremie, additional
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- 2024
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54. Baseline PSMA PET/CT as a predictive biomarker for toxicity and patient-reported outcomes in mCRPC patients undergoing 177Lu-PSMA radioligand therapy.
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Murthy, Vishnu, primary, Lokre, Ojaswita, additional, Perk, Timothy G., additional, Chen, Lucia, additional, Thin, Pan, additional, Nguyen, Kathleen, additional, Lira, Stephanie, additional, Alano, Rejah M., additional, Gafita, Andrei, additional, Czernin, Johannes, additional, and Calais, Jeremie, additional
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- 2024
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55. Exploring the prognostic value of the TRAQinform Profile applied to end-of-treatment PSMA PET/CT in patients with mCRPC and treated with 177Lu-PSMA radioligand therapy: A retrospective, single-center analysis.
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Murthy, Vishnu, primary, Lokre, Ojaswita, additional, Perk, Timothy G., additional, Thin, Pan, additional, Nguyen, Kathleen, additional, Chen, Lucia, additional, Gafita, Andrei, additional, Czernin, Johannes, additional, and Calais, Jeremie, additional
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- 2024
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56. Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study
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Lenis, Andrew T., Pooli, Aydin, Lec, Patrick M., Sadun, Taylor Y., Johnson, David C., Lebacle, Cedric, Fendler, Wolfgang P., Eiber, Matthias, Czernin, Johannes, Reiter, Robert E., and Calais, Jeremie
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- 2022
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57. 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial
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Calais, Jeremie, Ceci, Francesco, Eiber, Matthias, Hope, Thomas A, Hofman, Michael S, Rischpler, Christoph, Bach-Gansmo, Tore, Nanni, Cristina, Savir-Baruch, Bital, Elashoff, David, Grogan, Tristan, Dahlbom, Magnus, Slavik, Roger, Gartmann, Jeannine, Nguyen, Kathleen, Lok, Vincent, Jadvar, Hossein, Kishan, Amar U, Rettig, Matthew B, Reiter, Robert E, Fendler, Wolfgang P, and Czernin, Johannes
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Trials and Supportive Activities ,Prevention ,Clinical Research ,Prostate Cancer ,Urologic Diseases ,Biomedical Imaging ,Cancer ,Aging ,Bioengineering ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Aged ,Carboxylic Acids ,Contrast Media ,Cyclobutanes ,Edetic Acid ,Gallium Isotopes ,Gallium Radioisotopes ,Humans ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Oligopeptides ,Positron Emission Tomography Computed Tomography ,Prospective Studies ,Prostate-Specific Antigen ,Prostatectomy ,Prostatic Neoplasms ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundNational Comprehensive Cancer Network guidelines consider 18F-fluciclovine PET-CT for prostate cancer biochemical recurrence localisation after radical prostatectomy, whereas European Association of Urology guidelines recommend prostate-specific membrane antigen (PSMA) PET-CT. To the best of our knowledge, no prospective head-to-head comparison between these tests has been done so far. The aim of this study was to compare prospectively paired 18F-fluciclovine and PSMA PET-CT scans for localising biochemical recurrence of prostate cancer after radical prostatectomy in patients with low prostate-specific antigen (PSA) concentrations (
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- 2019
58. Preclinical evaluation of PSMA expression in response to androgen receptor blockade for theranostics in prostate cancer
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Lückerath, Katharina, Wei, Liu, Fendler, Wolfgang P, Evans-Axelsson, Susan, Stuparu, Andreea D, Slavik, Roger, Mona, Christine E, Calais, Jeremie, Rettig, Matthew, Reiter, Robert E, Herrmann, Ken, Radu, Caius G, Czernin, Johannes, and Eiber, Matthias
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Aging ,Urologic Diseases ,Clinical Trials and Supportive Activities ,Biomedical Imaging ,Prostate Cancer ,Radiation Oncology ,Cancer ,5.1 Pharmaceuticals ,PSMA ,Prostate cancer ,Ga-68-PSMA PET ,CT ,Androgen receptor blockade ,Radioligand therapy ,68Ga-PSMA PET/CT ,Medical Biochemistry and Metabolomics ,Clinical sciences ,Oncology and carcinogenesis - Abstract
BackgroundProstate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a promising yet not curative approach in castration-resistant (CR) prostate cancer (PC). Rational combination therapies may improve treatment efficacy. Here, we explored the effect of androgen receptor blockade (ARB) on PSMA expression visualized by PET and its potential additive effect when combined with 177Lu-PSMA RLT in a mouse model of prostate cancer.MethodsMice bearing human CRPC (C4-2 cells) xenografts were treated with 10 mg/kg enzalutamide (ENZ), with 50 mg/kg bicalutamide (BIC), or vehicle (control) for 21 days. PSMA expression was evaluated by 68Ga-PSMA11 PET/CT and quantified by flow cytometry of tumor fine needle aspirations before treatment and on days 23, 29, 34, and 39 post-therapy induction. For the RLT combination approach, mice bearing C4-2 tumors were treated with 10 mg/kg ENZ or vehicle for 21 days before receiving either 15 MBq (84 GBq/μmol) 177Lu-PSMA617 or vehicle. DNA damage was assessed as phospho-γH2A.X foci in tumor biopsies. Reduction of tumor volume on CT and survival were used as study endpoints.ResultsTumor growth was delayed by ARB while 68Ga-PSMA11 uptake increased up to 2.3-fold over time when compared to controls. ABR-induced upregulation of PSMA expression was confirmed by flow cytometry. Phospho-γH2A.X levels increased 1.8- and 3.4-fold at 48 h in response to single treatment ENZ or RLT and ENZ+RLT, respectively. Despite significantly greater DNA damage and persistent increase of PSMA expression at the time of RLT, no additional tumor growth retardation was observed in the ENZ+RLT group (vs. RLT only, p = 0.372 at day 81). Median survival did not improve significantly when ENZ was combined with RLT.ConclusionARB-mediated increases in PSMA expression in PC xenografts were evident by 68Ga-PSMA11 PET imaging and flow cytometry. 177Lu-PSMA617 effectively decreased C4-2 tumor size. However, while pre-treatment with ARB increased DNA damage significantly, it did not result in synergistic effects when combined with RLT.
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- 2018
59. Potential Impact of 68Ga-PSMA-11 PET/CT on the Planning of Definitive Radiation Therapy for Prostate Cancer
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Calais, Jeremie, Kishan, Amar U, Cao, Minsong, Fendler, Wolfgang P, Eiber, Matthias, Herrmann, Ken, Ceci, Francesco, Reiter, Robert E, Rettig, Matthew B, Hegde, John V, Shaverdian, Narek, King, Chris R, Steinberg, Michael L, Czernin, Johannes, and Nickols, Nicholas G
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Radiation Oncology ,Clinical Research ,Clinical Trials and Supportive Activities ,Aging ,Cancer ,Prostate Cancer ,Bioengineering ,Biomedical Imaging ,Urologic Diseases ,Aged ,Aged ,80 and over ,Cohort Studies ,Computer Simulation ,Edetic Acid ,Gallium Isotopes ,Gallium Radioisotopes ,Humans ,Lymphatic Metastasis ,Male ,Middle Aged ,Neoplasm Staging ,Oligopeptides ,Positron Emission Tomography Computed Tomography ,Prospective Studies ,Prostate ,Prostatic Neoplasms ,Radiopharmaceuticals ,Radiotherapy Planning ,Computer-Assisted ,Seminal Vesicles ,prostate cancer ,PSMA ,PET/CT ,initial staging ,definitive radiotherapy ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
Standard-of-care imaging for initial staging of prostate cancer (PCa) underestimates disease burden. Prostate-specific membrane antigen (PSMA) PET/CT detects PCa metastasis with superior accuracy, having a potential impact on the planning of definitive radiation therapy (RT) for nonmetastatic PCa. Our objectives were to determine how often definitive RT planning based on standard target volumes covers 68Ga-PSMA-11 PET/CT-defined disease and to assess the potential impact of 68Ga-PSMA-11 PET/CT on definitive RT planning. Methods: This was a post hoc analysis of an intention-to-treat population of 73 patients with localized PCa without prior local therapy who underwent 68Ga-PSMA PET/CT for initial staging as part of an investigational new drug trial. Eleven of the 73 were intermediate-risk (15%), 33 were high-risk (45%), 22 were very-high-risk (30%), and 7 were N1 (9.5%). Clinical target volumes (CTVs), which included the prostate, seminal vesicles, and (in accord with the Radiation Therapy Oncology Group consensus guidelines) pelvic lymph nodes (LNs), were contoured on the CT portion of the PET/CT images by a radiation oncologist masked to the PET findings. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the CTVs were considered to have a major potential impact on treatment planning. Results: All patients had one or more 68Ga-PSMA-11-positive primary prostate lesions. Twenty-five (34%) and 7 (9.5%) of the 73 patients had 68Ga-PSMA-11-positive pelvic LN and distant metastases, respectively. The sites of LN metastases in decreasing order of frequency were external iliac (20.5%), common iliac (13.5%), internal iliac (12.5%) obturator (12.5%), perirectal (4%), abdominal (4%), upper diaphragm (4%), and presacral (1.5%). The median size of the LN lesions was 6 mm (range, 4-24 mm). RT planning based on the CTVs covered 69 (94.5%) of the 73 primary lesions and 20 (80%) of the 25 pelvic LN lesions, on a per-patient analysis. Conclusion:68Ga-PSMA-11 PET/CT had a major impact on intended definitive RT planning for PCa in 12 (16.5%) of the 73 patients whose RT fields covered the prostate, seminal vesicles, and pelvic LNs and in 25 (37%) of the 66 patients whose RT fields covered the prostate and seminal vesicles but not the pelvic LNs.
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- 2018
60. Prostate-Specific Membrane Antigen PET/CT-Guided, Metastasis-Directed Radiotherapy for Oligometastatic Castration-Resistant Prostate Cancer.
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Nikitas, John, Rieger, Angela Castellanos, Farolfi, Andrea, Seyedroudbari, Ameen, Kishan, Amar U., Nickols, Nicholas G., Steinberg, Michael L., Valle, Luca F., Rettig, Matthew, Czernin, Johannes, and Calais, Jeremie
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- 2024
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61. Dosimetry of [177Lu]Lu-PSMA-Targeted Radiopharmaceutical Therapies in Patients with Prostate Cancer: A Comparative Systematic Review and Metaanalysis.
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Ells, Zachary, Grogan, Tristan R., Czernin, Johannes, Dahlbom, Magnus, and Calais, Jeremie
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- 2024
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62. Randomized Trial of Prostate-Specific Membrane Antigen PET/CT Before Definitive Radiotherapy for Unfavorable Intermediate- and High-Risk Prostate Cancer (PSMA-dRT Trial).
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Nikitas, John, Lam, Ethan, Booker, Kiara Adame, Fendler, Wolfgang P., Eiber, Matthias, Hadaschik, Boris, Herrmann, Ken, Hirmas, Nader, Lanzafame, Helena, Stuschke, Martin, Czernin, Johannes, Steinberg, Michael L., Nickols, Nicholas G., Kishan, Amar U., and Calais, Jeremie
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- 2024
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63. Differences and Common Ground in 177Lu-PSMA Radioligand Therapy Practice Patterns: International Survey of 95 Theranostic Centers.
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Farolfi, Andrea, Armstrong, Wesley R., Djaileb, Loic, Gafita, Andrei, Masatoshi Hotta, Allen-Auerbach, Martin, Unterrainer, Lena M., Fendler, Wolfgang P., Rettig, Matthew, Eiber, Matthias, Hofman, Michael S., Hadaschik, Boris, Herrmann, Ken, Czernin, Johannes, Calais, Jeremie, and Benz, Matthias R.
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- 2024
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64. Detection Threshold and Reproducibility of 68Ga-PSMA11 PET/CT in a Mouse Model of Prostate Cancer
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Lückerath, Katharina, Stuparu, Andreea D, Wei, Liu, Kim, Woosuk, Radu, Caius G, Mona, Christine E, Calais, Jeremie, Rettig, Matthew, Reiter, Robert E, Czernin, Johannes, Slavik, Roger, Herrmann, Ken, Eiber, Matthias, and Fendler, Wolfgang P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Urologic Diseases ,Biomedical Imaging ,Bioengineering ,Prostate Cancer ,Good Health and Well Being ,Animals ,Biological Transport ,Cell Line ,Tumor ,Disease Models ,Animal ,Edetic Acid ,Gallium Isotopes ,Gallium Radioisotopes ,Gene Expression Regulation ,Neoplastic ,Image Processing ,Computer-Assisted ,Male ,Mice ,Mice ,Inbred C57BL ,Oligopeptides ,Positron Emission Tomography Computed Tomography ,Prostatic Neoplasms ,Reproducibility of Results ,PSMA ,prostate cancer ,PET ,threshold ,reproducibility ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
To improve prostate-specific membrane antigen (PSMA)-targeted theranostic approaches, robust murine models of prostate cancer are needed. However, important characteristics of preclinical PSMA imaging-that is, the reproducibility of the imaging signal and the relationship between quantitative cell surface PSMA expression and lesion detectability with small-animal PET/CT-have not been defined yet. Methods: Murine prostate cancer RM1 sublines (ras myc transformed cells of C57BL/6 prostate origin) expressing varying levels of human PSMA were injected into the shoulder of C57BL/6 mice on day 0. 68Ga-PSMA11 PET/CT was performed on days 7 and 8 and interpreted by 2 masked readers to determine interday and interreader reproducibility. PSMA expression was quantified on days 7 and 8 by flow cytometry of fine-needle aspiration tumor biopsy samples. Cell surface PSMA expression was correlated with PET signal. The threshold for PET positivity was based on the clinical Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria. Results: The maximum and average percentages of injected 68Ga-PSMA11 activity per gram of tissue (%IA/g) correlated nearly perfectly as determined by 2 independent readers and on 2 separate days (intraclass correlation coefficient, 1.00/0.89 and 0.95/0.88, respectively). The number of PSMA molecules per cell increased from the RM1-yellow fluorescent protein subline (PSMA-; 2,000/cell) to the RM1-low subline (PSMA+; 17,000/cell), the RM1-medium subline (PSMA++; 22,000/cell), and the RM1-PGLS subline (PSMA-positive, green fluorescent protein-positive, and luciferase-positive; PSMA+++; 45,000/cell). Expression levels correlated with the visual positivity rate on 68Ga-PSMA11 PET and with the PSMA PET %IA/g. The PSMA threshold for PET positivity was approximately 20,000 per cell. Signal correlation was close at lower PSMA levels (RM1-low to RM1-medium; 10-23 %IA/g) but was lost at higher PSMA levels (RM1-medium to RM1-PGLS; 23-27 %IA/g). Conclusion: The in vivo relationship between 68Ga-PSMA11 PET/CT and PSMA expression level in a murine model of prostate cancer was robust for lower cell surface PSMA expression levels (≤22,000/cell). Thus, preclinical 68Ga-PSMA11 PET/CT can be used as an imaging biomarker to test PSMA-targeted interventions in murine models.
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- 2018
65. 18F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study
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Patel, Chirag B, Fazzari, Elisa, Chakhoyan, Ararat, Yao, Jingwen, Raymond, Catalina, Nguyen, Huytram, Manoukian, Jasmine, Nguyen, Nhung, Pope, Whitney, Cloughesy, Timothy F, Nghiemphu, Phioanh L, Czernin, Johannes, Lai, Albert, and Ellingson, Benjamin M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Neurosciences ,Brain Cancer ,Biomedical Imaging ,Cancer ,Brain Disorders ,Clinical Research ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Adolescent ,Adult ,Aged ,Biomarkers ,Tumor ,Brain ,Brain Neoplasms ,Contrast Media ,Cross-Sectional Studies ,Dihydroxyphenylalanine ,Female ,Glioma ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Positron-Emission Tomography ,Preoperative Period ,Prognosis ,Radiopharmaceuticals ,Retrospective Studies ,Survival Analysis ,Young Adult ,F-18-FDOPA PET ,Biomarker ,MRI ,18F-FDOPA PET ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
IntroductionTo report the potential value of pre-operative 18F-FDOPA PET and anatomic MRI in diagnosis and prognosis of glioma patients.MethodsForty-five patients with a pathological diagnosis of glioma with pre-operative 18F-FDOPA PET and anatomic MRI were retrospectively examined. The volume of contrast enhancement and T2 hyperintensity on MRI images along with the ratio of maximum 18F-FDOPA SUV in tumor to normal tissue (T/N SUVmax) were measured and used to predict tumor grade, molecular status, and overall survival (OS).ResultsA significant correlation was observed between WHO grade and: the volume of contrast enhancement (r = 0.67), volume of T2 hyperintensity (r = 0.42), and 18F-FDOPA uptake (r = 0.60) (P
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- 2018
66. Impact of 68Ga-PSMA-11 PET/CT on the Management of Prostate Cancer Patients with Biochemical Recurrence
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Calais, Jeremie, Fendler, Wolfgang P, Eiber, Matthias, Gartmann, Jeannine, Chu, Fang-I, Nickols, Nicholas G, Reiter, Robert E, Rettig, Matthew B, Marks, Leonard S, Ahlering, Thomas E, Huynh, Linda M, Slavik, Roger, Gupta, Pawan, Quon, Andrew, Allen-Auerbach, Martin S, Czernin, Johannes, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Urologic Diseases ,Aging ,Prostate Cancer ,Biomedical Imaging ,Aged ,Edetic Acid ,Gallium Isotopes ,Gallium Radioisotopes ,Humans ,Male ,Oligopeptides ,Positron Emission Tomography Computed Tomography ,Prostatic Neoplasms ,Recurrence ,prostate cancer ,biochemical recurrence ,PET/CT ,Ga-68-PSMA ,impact on implemented management ,68Ga-PSMA ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
In this prospective survey of referring physicians, we investigated whether and how 68Ga-labeled prostate-specific membrane antigen 11 (68Ga-PSMA-11) PET/CT affects the implemented management of prostate cancer patients with biochemical recurrence (BCR). Methods: We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median prostate-specific antigen value, 1.7 ng/mL; range, 0.05-202 ng/mL). Referring physicians completed one questionnaire before the scan to indicate the treatment plan without 68Ga-PSMA-11 PET/CT information (Q1; n = 101), one immediately after the scan to denote intended management changes (Q2; n = 101), and one 3-6 mo later to document the final implemented management (Q3; n = 56). The implemented management was also obtained via electronic chart review or patient contact (n = 45). Results: A complete documented management strategy (Q1 + Q2 + implemented management) was available for 101 of 161 patients (63%). Seventy-six of these (75%) had a positive 68Ga-PSMA-11 PET/CT result. The implemented management differed from the prescan intended management (Q1) in 54 of 101 patients (53%). The postscan intended management (Q2) differed from the prescan intended management (Q1) in 62 of 101 patients (61%); however, these intended changes were not implemented in 29 of 62 patients (47%). Pelvic nodal and extrapelvic metastatic disease on 68Ga-PSMA-11 PET/CT (PSMA T0N1M0 and PSMA T0N1M1 patterns) was significantly associated with implemented management changes (P = 0.001 and 0.05). Conclusion: Information from 68Ga-PSMA-11 PET/CT brings about management changes in more than 50% of prostate cancer patients with BCR (54/101; 53%). However, intended management changes early after 68Ga-PSMA-11 PET/CT frequently differ from implemented management changes.
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- 2018
67. 68Ga-PSMA-11 PET/CT Mapping of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy in 270 Patients with a PSA Level of Less Than 1.0 ng/mL: Impact on Salvage Radiotherapy Planning
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Calais, Jeremie, Czernin, Johannes, Cao, Minsong, Kishan, Amar U, Hegde, John V, Shaverdian, Narek, Sandler, Kiri, Chu, Fang-I, King, Chris R, Steinberg, Michael L, Rauscher, Isabel, Schmidt-Hegemann, Nina-Sophie, Poeppel, Thorsten, Hetkamp, Philipp, Ceci, Francesco, Herrmann, Ken, Fendler, Wolfgang P, Eiber, Matthias, and Nickols, Nicholas G
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Prostate Cancer ,Urologic Diseases ,Radiation Oncology ,Cancer ,Clinical Research ,Clinical Trials and Supportive Activities ,Adult ,Aged ,Aged ,80 and over ,Edetic Acid ,Gallium Isotopes ,Gallium Radioisotopes ,Humans ,Image Processing ,Computer-Assisted ,Male ,Middle Aged ,Oligopeptides ,Positron Emission Tomography Computed Tomography ,Prostate-Specific Antigen ,Prostatectomy ,Prostatic Neoplasms ,Radiotherapy Planning ,Computer-Assisted ,Recurrence ,Salvage Therapy ,prostate cancer ,PSMA ,PET/CT ,recurrence ,salvage radiotherapy ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
Target volume delineations for prostate cancer (PCa) salvage radiotherapy (SRT) after radical prostatectomy are usually drawn in the absence of visibly recurrent disease. 68Ga-labeled prostate-specific membrane antigen (PSMA-11) PET/CT detects recurrent PCa with sensitivity superior to standard-of-care imaging at serum prostate-specific antigen (PSA) values low enough to affect target volume delineations for routine SRT. Our objective was to map the recurrence pattern of PCa early biochemical recurrence (BCR) after radical prostatectomy with 68Ga-PSMA-11 PET/CT in patients with serum PSA levels of less than 1 ng/mL, determine how often consensus clinical target volumes (CTVs) based on the Radiation Therapy Oncology Group (RTOG) guidelines cover 68Ga-PSMA-11 PET/CT-defined disease, and assess the potential impact of 68Ga-PSMA-11 PET/CT on SRT. Methods: This was a post hoc analysis of an intention-to-treat population of 270 patients who underwent 68Ga-PSMA-11 PET/CT at 4 institutions for BCR after prostatectomy without prior radiotherapy at a PSA level of less than 1 ng/mL. RTOG consensus CTVs that included both the prostate bed and the pelvic lymph nodes were contoured on the CT dataset of the PET/CT image by a radiation oncologist masked to the PET component. 68Ga-PSMA-11 PET/CT images were analyzed by a nuclear medicine physician. 68Ga-PSMA-11-positive lesions not covered by planning volumes based on the consensus CTVs were considered to have a potential major impact on treatment planning. Results: The median PSA level at the time of 68Ga-PSMA-11 PET/CT was 0.48 ng/mL (range, 0.03-1 ng/mL). One hundred thirty-two of 270 patients (49%) had a positive 68Ga-PSMA-11 PET/CT result. Fifty-two of 270 (19%) had at least one PSMA-11-positive lesion not covered by the consensus CTVs. Thirty-three of 270 (12%) had extrapelvic PSMA-11-positive lesions, and 19 of 270 (7%) had PSMA-11-positive lesions within the pelvis but not covered by the consensus CTVs. The 2 most common 68Ga-PSMA-11-positive lesion locations outside the consensus CTVs were bone (23/52, 44%) and perirectal lymph nodes (16/52, 31%). Conclusion: Post hoc analysis of 68Ga-PSMA-11 PET/CT implied a major impact on SRT planning in 52 of 270 patients (19%) with PCa early BCR (PSA < 1.0 ng/mL). This finding justifies a randomized imaging trial of SRT with or without 68Ga-PSMA-11 PET/CT investigating its potential benefit on clinical outcome.
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- 2018
68. Establishing 177Lu-PSMA-617 Radioligand Therapy in a Syngeneic Model of Murine Prostate Cancer
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Fendler, Wolfgang P, Stuparu, Andreea D, Evans-Axelsson, Susan, Lückerath, Katharina, Wei, Liu, Kim, Woosuk, Poddar, Soumya, Said, Jonathan, Radu, Caius G, Eiber, Matthias, Czernin, Johannes, Slavik, Roger, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Cancer ,Biomedical Imaging ,Urologic Diseases ,Animals ,Cell Line ,Tumor ,DNA Breaks ,Double-Stranded ,Dipeptides ,Fluorodeoxyglucose F18 ,Heterocyclic Compounds ,1-Ring ,Humans ,Immunohistochemistry ,Lutetium ,Male ,Mice ,Mice ,Inbred C57BL ,Neoplasm Transplantation ,Positron-Emission Tomography ,Prostate-Specific Antigen ,Prostatic Neoplasms ,Radiopharmaceuticals ,Tissue Distribution ,Tumor Burden ,syngeneic ,PSMA ,prostate cancer ,Lu-177 ,specific activity ,177Lu ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
Clinical 177Lu-PSMA-617 radioligand therapy (RLT) is applied in advanced-stage prostate cancer. However, to the best of our knowledge murine models to study the biologic effects of various activity levels have not been established. The aim of this study was to optimize specific and total activity for 177Lu-PSMA-617 RLT in a syngeneic model of murine prostate cancer. Methods: Murine-reconstituted, oncogene-driven prostate cancer cells (0.1 × 106) (RM1), transduced to express human prostate-specific membrane antigen (PSMA), were injected into the left flank of C57Bl6 immunocompetent mice. RLT was performed by administering a single tail vein injection of 177Lu-PSMA-617 at different formulations for specific (60 MBq at high, 62 MBq/nmol; intermediate, 31 MBq/nmol; or low 15 MBq/nmol specific activity) or total activity (30, 60, or 120 MBq). Organ distribution was determined by ex vivo γ-counter measurement. DNA double-strand breaks were measured using anti-gamma-H2A.X (phospho S139) immunohistochemistry. Efficacy was assessed by serial CT tumor volumetry and 18F-FDG PET metabolic volume. Toxicity was evaluated 4 wk after the start of RLT. Results: Mean tumor-to-kidney ratios ± SEM were 19 ± 5, 10 ± 5, and 2 ± 0 for high, intermediate, and low (each n = 3) specific activity, respectively. Four of 6 (67%) mice treated with intermediate or high specific activity and none of 6 (0%) mice treated with low specific activity or formulation demonstrated significant DNA double-strand breaks (≥5% γ-H2A.X-positive cells). High when compared with intermediate or low specific activity resulted in a lower mean ± SEM tumor load by histopathology (vital tissue, 4 ± 2 vs. 8 ± 3 mm2; n = 3 vs. 6), day-4 18F-FDG PET (metabolic volume, 87 ± 23 vs. 118 ± 14 mm3; n = 6 vs. 12), and day-7 CT (volume, 323 ± 122 vs. 590 ± 46 mm3; n = 3 vs. 6; P = 0.039). 177Lu-PSMA-617 (120 MBq) with high specific activity induced superior tumor growth inhibition (P = 0.021, n = 5/group) without subacute hematologic toxicity (n = 3/group). Conclusion:177Lu-PSMA-617 (120 MBq) and high specific activity resulted in the highest efficacy in a syngeneic model of murine prostate cancer. The model will be useful for studying the effects of PSMA-directed RLT combined with potentially synergistic pharmacologic approaches.
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- 2017
69. Most of the Intended Management Changes After 68Ga-DOTATATE PET/CT Are Implemented
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Calais, Jeremie, Czernin, Johannes, Eiber, Matthias, Fendler, Wolfgang P, Gartmann, Jeannine, Heaney, Anthony P, Hendifar, Andrew E, Pisegna, Joseph R, Hecht, J Randolph, Wolin, Edward M, Slavik, Roger, Gupta, Pawan, Quon, Andrew, Schiepers, Christiaan, Allen-Auerbach, Martin S, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Cancer ,Biomedical Imaging ,Clinical Trials and Supportive Activities ,Aged ,Case Management ,Drugs ,Investigational ,Female ,Humans ,Image Processing ,Computer-Assisted ,Investigational New Drug Application ,Male ,Middle Aged ,Neuroendocrine Tumors ,Organometallic Compounds ,Positron Emission Tomography Computed Tomography ,Positron-Emission Tomography ,Prospective Studies ,Radiopharmaceuticals ,Receptors ,Somatostatin ,Surveys and Questionnaires ,neuroendocrine tumors ,somatostatin receptor ,PET/CT ,DOTATATE ,impact on implemented management ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
In this prospective referring-physician-based survey, we investigated the definite clinical impact of 68Ga-DOTATATE PET/CT on managing patients with neuroendocrine tumors (NETs). Methods: We prospectively studied 130 patients with 68Ga-DOTATATE PET/CT referred for initial or subsequent management decisions (NCT02174679). Referring physicians completed one questionnaire before the scan (Q1) to indicate the treatment plan without PET/CT information, one immediately after review of the imaging report to denote intended management changes (Q2), and one 6 mo later (Q3) to verify whether intended changes were in fact implemented. To further validate the Q3 responses, a systematic electronic chart review was conducted. Results: All 3 questionnaires were completed by referring physicians for 96 of 130 patients (74%). 68Ga-DOTATATE PET/CT resulted in intended management changes (Q2) in 48 of 96 patients (50%). These changes were finally implemented (Q3) in 36 of 48 patients (75%). Q3 responses were confirmed in all patients with an available electronic chart (36/96; 38%). Conclusion: This prospective study confirmed a significant impact of 68Ga-DOTATATE PET/CT on the intended management of patients with NETs (50% of changes) and notably demonstrated a high implementation rate (75%) of these intended management changes.
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- 2017
70. Systemic and Tumor-directed Therapy for Oligorecurrent Metastatic Prostate Cancer (SATURN): Primary Endpoint Results from a Phase 2 Clinical Trial
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Nikitas, John, primary, Rettig, Matthew, additional, Shen, John, additional, Reiter, Robert, additional, Lee, Alan, additional, Steinberg, Michael L., additional, Valle, Luca F., additional, Sachdeva, Ankush, additional, Romero, Tahmineh, additional, Calais, Jeremie, additional, Czernin, Johannes, additional, Nickols, Nicholas G., additional, and Kishan, Amar U., additional
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- 2024
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71. Development of a LRRC15-Targeted Radio-Immunotheranostic Approach to Deplete Pro-tumorigenic Mechanisms and Immunotherapy Resistance
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Storey, Claire M, primary, Altai, Mohamed, additional, Lückerath, Katharina, additional, Zedan, Wahed, additional, Zhu, Henan, additional, Trajkovic-Arsic, Marija, additional, Park, Julie, additional, Peekhaus, Norbert, additional, Siveke, Jens, additional, Lilljebjörn, Henrik, additional, Abou, Diane, additional, Marks, Haley, additional, Ulmert, Enna, additional, Lilja, Hans, additional, Ridley, Alexander, additional, Safi, Marcella, additional, Yuen, Constance, additional, Geres, Susanne, additional, Mao, Liqun, additional, Cheng, Michael, additional, Czernin, Johannes, additional, Herrmann, Ken, additional, Bentolila, Laurent, additional, Yang, Xia, additional, Fioretos, Thoas, additional, Graeber, Thomas, additional, Sjöström, Kjell, additional, Damoiseaux, Robert, additional, Thorek, Daniel, additional, and Ulmert, David, additional
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- 2024
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72. Differences and Common Ground in177Lu-PSMA Radioligand Therapy Practice Patterns: International Survey of 95 Theranostic Centers
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Farolfi, Andrea, primary, Armstrong, Wesley R., additional, Djaileb, Loic, additional, Gafita, Andrei, additional, Hotta, Masatoshi, additional, Allen-Auerbach, Martin, additional, Unterrainer, Lena M., additional, Fendler, Wolfgang P., additional, Rettig, Matthew, additional, Eiber, Matthias, additional, Hofman, Michael S., additional, Hadaschik, Boris, additional, Herrmann, Ken, additional, Czernin, Johannes, additional, Calais, Jeremie, additional, and Benz, Matthias R., additional
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- 2024
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73. [68Ga]Ga-FAPI-46 PET in a Borderline Ovarian Tumor
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Unterrainer, Lena M., primary, Memarzadeh, Sanaz, additional, Moatamed, Neda A., additional, Benz, Matthias R., additional, Czernin, Johannes, additional, and Calais, Jeremie, additional
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- 2024
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74. Expanding the Mission and Influence of SNMMI
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Pappas, Virginia, primary and Czernin, Johannes, additional
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- 2024
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75. Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study
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Gafita, Andrei, Calais, Jeremie, Grogan, Tristan R, Hadaschik, Boris, Wang, Hui, Weber, Manuel, Sandhu, Shahneen, Kratochwil, Clemens, Esfandiari, Rouzbeh, Tauber, Robert, Zeldin, Anna, Rathke, Hendrik, Armstrong, Wesley R, Robertson, Andrew, Thin, Pan, D'Alessandria, Calogero, Rettig, Matthew B, Delpassand, Ebrahim S, Haberkorn, Uwe, Elashoff, David, Herrmann, Ken, Czernin, Johannes, Hofman, Michael S, Fendler, Wolfgang P, and Eiber, Matthias
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- 2021
- Full Text
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76. Detection of immune responses after immunotherapy in glioblastoma using PET and MRI
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Antonios, Joseph P, Soto, Horacio, Everson, Richard G, Moughon, Diana L, Wang, Anthony C, Orpilla, Joey, Radu, Caius, Ellingson, Benjamin M, Lee, Jason T, Cloughesy, Timothy, Phelps, Michael E, Czernin, Johannes, Liau, Linda M, and Prins, Robert M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Orphan Drug ,Brain Cancer ,Neurosciences ,Cancer ,Immunization ,Brain Disorders ,Bioengineering ,Rare Diseases ,Immunotherapy ,Biomedical Imaging ,Vaccine Related ,Inflammatory and immune system ,Animals ,Cell Line ,Female ,Glioblastoma ,Humans ,Magnetic Resonance Imaging ,Mice ,Mice ,Inbred C57BL ,Positron-Emission Tomography ,glioblastoma ,PET ,MRI ,immunotherapy ,checkpoint blockade - Abstract
Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI. Orthotopic malignant gliomas were established in syngeneic immunocompetent mice and then treated with dendritic cell (DC) vaccination and/or PD-1 mAb blockade. Mice were then imaged with [18F]-FAC PET/CT and MRI with i.v. contrast. The ratio of contrast enhancement on MRI to normalized PET probe uptake, which we term the immunotherapeutic response index, delineated specific regions of immune inflammatory activity. On postmortem examination, FACS-based enumeration of intracranial tumor-infiltrating lymphocytes directly correlated with quantitative [18F]-FAC PET probe uptake. Three patients with GBM undergoing treatment with tumor lysate-pulsed DC vaccination and PD-1 mAb blockade were also imaged before and after therapy using MRI and a clinical PET probe for dCK. Unlike in mice, [18F]-FAC is rapidly catabolized in humans; thus, we used another dCK PET probe, [18F]-clofarabine ([18F]-CFA), that may be more clinically relevant. Enhanced [18F]-CFA PET probe accumulation was identified in tumor and secondary lymphoid organs after immunotherapy. Our findings identify a noninvasive modality capable of imaging the host antitumor immune response against intracranial tumors.
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- 2017
77. Activation of the “Splenocardiac Axis” by electronic and tobacco cigarettes in otherwise healthy young adults
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Boas, Zachary, Gupta, Pawan, Moheimani, Roya S, Bhetraratana, May, Yin, Fen, Peters, Kacey M, Gornbein, Jeffrey, Araujo, Jesus A, Czernin, Johannes, and Middlekauff, Holly R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Cardiovascular ,Clinical Trials and Supportive Activities ,Heart Disease ,Tobacco ,Tobacco Smoke and Health ,Biomedical Imaging ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Adult ,Aorta ,Case-Control Studies ,Electronic Nicotine Delivery Systems ,Female ,Fluorodeoxyglucose F18 ,Heart ,Humans ,Male ,Muscle ,Skeletal ,Positron Emission Tomography Computed Tomography ,Radiopharmaceuticals ,Smoking ,Spleen ,Arterial inflammation ,electronic cigarettes ,FDG-PET ,CT ,hematopoietic activation ,tobacco cigarettes ,Tobacco and electronic cigarettes ,Inflammation ,Positron emission tomography ,Vascular disease ,FDG‐PET/CT ,Physiology ,Medical Physiology ,Medical physiology - Abstract
The "Splenocardiac Axis" describes an inflammatory signaling network underlying acute cardiac ischemia, characterized by sympathetic nerve stimulation of hematopoietic tissues, such as the bone marrow and spleen, which then release proinflammatory monocytes that populate atherosclerotic plaques, thereby promoting ischemic heart disease. Electronic (e) cigarettes, like tobacco cigarettes trigger sympathetic nerve activation, but virtually nothing is known about their influence on hematopoietic and vascular tissues and cardiovascular risks. The objective of this study was to determine if the Splenocardiac Axis is activated in young adults who habitually use either tobacco or e-cigarettes. In otherwise healthy humans who habitually use tobacco cigarettes or e-cigarettes (not both), we used 18F-flurorodeoxyglucose positron emission tomography/computer tomography (FDG-PET/CT) to test the hypothesis that tobacco or e-cigarettes increased metabolic activity of the hematopoietic and vascular tissues. FDG uptake in the spleen increased from nonuser controls (1.62 ± 0.07), to the e-cigarette users (1.73 ± 0.04), and was highest in tobacco cigarette smokers (1.82 ± 0.09; monotone P = 0.05). Similarly, FDG uptake in the aorta increased from the nonuser controls (1.87 ± 0.07) to the e-cigarette users (1.98 ± 0.07), and was highest in tobacco cigarette smokers (2.10 ± 0.07; monotone P = 0.04). FDG uptake in the skeletal muscle, which served as a control tissue, was not different between the groups. In conclusion, these findings are consistent with activation of the Splenocardiac Axis by emissions from tobacco cigarettes and e-cigarettes. This activation suggests a mechanism by which tobacco cigarettes, and potentially e-cigarettes, may lead to increased risk of future cardiovascular events.
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- 2017
78. ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways.
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Le, Thuc M, Poddar, Soumya, Capri, Joseph R, Abt, Evan R, Kim, Woosuk, Wei, Liu, Uong, Nhu T, Cheng, Chloe M, Braas, Daniel, Nikanjam, Mina, Rix, Peter, Merkurjev, Daria, Zaretsky, Jesse, Kornblum, Harley I, Ribas, Antoni, Herschman, Harvey R, Whitelegge, Julian, Faull, Kym F, Donahue, Timothy R, Czernin, Johannes, and Radu, Caius G
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Animals ,Mice ,Inbred C57BL ,Humans ,Mice ,Ribonucleotide Reductases ,Deoxycytidine Kinase ,Nucleotides ,DNA Replication ,Female ,Biosynthetic Pathways ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Ataxia Telangiectasia Mutated Proteins ,Rare Diseases ,Biotechnology ,Childhood Leukemia ,Pediatric ,Pediatric Cancer ,Orphan Drug ,Cancer ,Hematology ,5.1 Pharmaceuticals ,2.1 Biological and endogenous factors - Abstract
Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the activity of their respective rate-limiting enzymes, ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK), via distinct molecular mechanisms. Quantification of nucleotide biosynthesis in ATR-inhibited acute lymphoblastic leukemia (ALL) cells reveals substantial remaining de novo and salvage activities, and could not eliminate the disease in vivo. However, targeting these remaining activities with RNR and dCK inhibitors triggers lethal replication stress in vitro and long-term disease-free survival in mice with B-ALL, without detectable toxicity. Thus the functional interplay between alternative nucleotide biosynthetic routes and ATR provides therapeutic opportunities in leukemia and potentially other cancers.Leukemic cells depend on the nucleotide synthesis pathway to proliferate. Here the authors use metabolomics and proteomics to show that inhibition of ATR reduced the activity of these pathways thus providing a valuable therapeutic target in leukemia.
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- 2017
79. Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway
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Barrio, Martin J, Spick, Claudio, Radu, Caius G, Lassmann, Michael, Eberlein, Uta, Allen-Auerbach, Martin, Schiepers, Christiaan, Slavik, Roger, Czernin, Johannes, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Urologic Diseases ,Digestive Diseases ,Cancer ,Liver Disease ,Clinical Research ,Bioengineering ,5.1 Pharmaceuticals ,4.1 Discovery and preclinical testing of markers and technologies ,Generic health relevance ,Absorption ,Radiation ,Adenine Nucleotides ,Aged ,Arabinonucleosides ,Clofarabine ,Deoxycytidine Kinase ,Deoxyribonucleosides ,Female ,Fluorine Radioisotopes ,Humans ,Male ,Metabolic Clearance Rate ,Middle Aged ,Molecular Imaging ,Organ Specificity ,Positron-Emission Tomography ,Radiation Dosage ,Radiopharmaceuticals ,Signal Transduction ,Tissue Distribution ,Whole-Body Counting ,PET ,dosimetry ,clofarabine ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
18F-clofarabine, a nucleotide purine analog, is a substrate for deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. 18F-clofarabine might be used to measure dCK expression and thus serve as a predictive biomarker for tumor responses to dCK-dependent prodrugs or small-molecule dCK inhibitors, respectively. As a prerequisite for clinical translation, we determined the human whole-body and organ dosimetry of 18F-clofarabine. Methods: Five healthy volunteers were injected intravenously with 232.4 ± 1.5 MBq of 18F-clofarabine. Immediately after tracer injection, a dynamic scan of the entire chest was acquired for 30 min. This was followed by 3 static whole-body scans at 45, 90, and 135 min after tracer injection. Regions of interest were drawn around multiple organs on the CT scan and copied to the PET scans. Organ activity was determined and absorbed dose was estimated with OLINDA/EXM software. Results: The urinary bladder (critical organ), liver, kidney, and spleen exhibited the highest uptake. For an activity of 250 MBq, the absorbed doses in the bladder, liver, kidney, and spleen were 58.5, 6.6, 6.3, and 4.3 mGy, respectively. The average effective dose coefficient was 5.1 mSv. Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine whether 18F-clofarabine may serve as a predictive biomarker for responses to dCK-dependent prodrugs or small-molecule dCK inhibitors.
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- 2017
80. 68Ga-DOTATATE PET/CT Interobserver Agreement for Neuroendocrine Tumor Assessment: Results of a Prospective Study on 50 Patients
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Fendler, Wolfgang Peter, Barrio, Martin, Spick, Claudio, Allen-Auerbach, Martin, Ambrosini, Valentina, Benz, Matthias, Bluemel, Christina, Grewal, Ravinder Kaur, Lapa, Constantin, Miederer, Matthias, Nicolas, Guillaume, Schuster, Tibor, Czernin, Johannes, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Cancer ,Clinical Research ,Clinical Trials and Supportive Activities ,Bioengineering ,Digestive Diseases ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Adult ,Aged ,False Positive Reactions ,Female ,Humans ,Image Enhancement ,Male ,Middle Aged ,Neuroendocrine Tumors ,Observer Variation ,Organometallic Compounds ,Positron Emission Tomography Computed Tomography ,Prospective Studies ,Radiopharmaceuticals ,Reproducibility of Results ,Sensitivity and Specificity ,neuroendocrine tumor ,agreement ,reproducibility ,PET/CT ,DOTATATE ,interobserver ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
We evaluated observer agreement for 68Ga-DOTATATE PET/CT interpretations in patients with neuroendocrine tumor (NET).Methods68Ga-DOTATATE PET/CT was performed on 50 patients with known or suspected NET of the small bowel (n = 19), pancreas (n = 14), lung (n = 4), or other location (n = 13). The images were reviewed by 7 observers, who used a standardized interpretation approach. The observers were classified as having a low level of experience (
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- 2017
81. Reporter gene imaging of targeted T cell immunotherapy in recurrent glioma
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Keu, Khun Visith, Witney, Timothy H, Yaghoubi, Shahriar, Rosenberg, Jarrett, Kurien, Anita, Magnusson, Rachel, Williams, John, Habte, Frezghi, Wagner, Jamie R, Forman, Stephen, Brown, Christine, Allen-Auerbach, Martin, Czernin, Johannes, Tang, Winson, Jensen, Michael C, Badie, Behnam, and Gambhir, Sanjiv S
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Biomedical Imaging ,Gene Therapy ,Brain Cancer ,Cancer ,Immunization ,Vaccine Related ,Genetics ,Biotechnology ,Orphan Drug ,Bioengineering ,Brain Disorders ,Rare Diseases ,Development of treatments and therapeutic interventions ,5.2 Cellular and gene therapies ,Aged ,Brain Neoplasms ,Female ,Gene Expression ,Genes ,Reporter ,Genetic Therapy ,Glioma ,Humans ,Immunotherapy ,Interleukin-13 ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Positron-Emission Tomography ,Prospective Studies ,Receptors ,Antigen ,T-Cell ,T-Lymphocytes ,Cytotoxic ,Thymidine Kinase ,Biological Sciences ,Medical and Health Sciences - Abstract
High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.
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- 2017
82. Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer
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Momcilovic, Milica, Bailey, Sean T, Lee, Jason T, Fishbein, Michael C, Magyar, Clara, Braas, Daniel, Graeber, Thomas, Jackson, Nicholas J, Czernin, Johannes, Emberley, Ethan, Gross, Matthew, Janes, Julie, Mackinnon, Andy, Pan, Alison, Rodriguez, Mirna, Works, Melissa, Zhang, Winter, Parlati, Francesco, Demo, Susan, Garon, Edward, Krysan, Kostyantyn, Walser, Tonya C, Dubinett, Steven M, Sadeghi, Saman, Christofk, Heather R, and Shackelford, David B
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Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Lung ,Biomedical Imaging ,Lung Cancer ,AMP-Activated Protein Kinases ,Animals ,Apoptosis ,Autophagy ,Benzeneacetamides ,Carbon Radioisotopes ,Carcinoma ,Non-Small-Cell Lung ,Cell Line ,Tumor ,ErbB Receptors ,Erlotinib Hydrochloride ,Fluorodeoxyglucose F18 ,Glutaminase ,Glutamine ,Humans ,Lung Neoplasms ,Mice ,Mice ,SCID ,Mutation ,RNA Interference ,Radiopharmaceuticals ,Thiadiazoles ,Transplantation ,Heterologous ,AMPK ,CB-839 ,EGFR ,PET imaging ,erlotinib ,glutamine ,lung cancer ,metabolic crisis ,Medical Physiology ,Biological sciences - Abstract
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors. Tumor cells undergo metabolic crisis and cell death, resulting in rapid tumor regression in vivo in mouse NSCLC xenografts. Consistently, positron emission tomography (PET) imaging with 18F-fluoro-2-deoxyglucose (18F-FDG) and 11C-glutamine (11C-Gln) of xenografts indicated reduced glucose and glutamine uptake in tumors following treatment with CB-839 + erlotinib. Therefore, PET imaging with 18F-FDG and 11C-Gln tracers can be used to non-invasively measure metabolic response to CB-839 and erlotinib combination therapy.
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- 2017
83. The incidence of thyroid cancer in focal hypermetabolic thyroid lesions
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Barrio, Martin, Czernin, Johannes, Yeh, Michael W, Diaz, Miguel F Palma, Gupta, Pawan, Allen-Auerbach, Martin, Schiepers, Christiaan, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Biomedical Imaging ,Clinical Research ,Rare Diseases ,Adult ,Aged ,Aged ,80 and over ,Female ,Fluorine Radioisotopes ,Fluorodeoxyglucose F18 ,Humans ,Incidence ,Incidental Findings ,Male ,Middle Aged ,Positron Emission Tomography Computed Tomography ,Radiopharmaceuticals ,Retrospective Studies ,Thyroid Gland ,Thyroid Neoplasms ,Young Adult ,fluorine-18 fluorodeoxyglucose ,incidental findings ,PET ,thyroid ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
BackgroundThe clinical significance of incidental thyroid abnormalities discovered in fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) (FDG PET/CT) studies remains controversial. The aim of this large retrospective study was to (a) determine the prevalence of focal F-FDG thyroid uptake on whole-body F-FDG PET/CT studies carried out for nonthyroid cancers and (b) to test whether intense focal F-FDG thyroid uptake is associated with malignancy.Materials and methodsA total of 11 921 F-FDG PET/CT studies in 6216 patients carried out at our institution between January 2012 and December 2014 were analyzed. We retrospectively reviewed the medical records of these patients. Eight hundred and forty-five/6216 (13.6%) patients had a thyroid incidentaloma on the basis of the clinical F-FDG PET/CT report. One hundred and sixty/845 (18.9%) of these underwent ultrasound and 98 (61.3%) of these underwent a fine-needle aspiration (FNA). Twenty-six of these 98 (26.5%) patients underwent thyroidectomy. Thyroid lesion and background standardized uptake value (SUVs) for each patient were measured upon review of the F-FDG PET/CT study. We measured maximum standardized uptake value (SUVmax), thyroid to background TL/TBG, thyroid to bloodpool TL/BP and thyroid to liver TL/L ratios in benign and malignant lesions. Receiver operating curves were calculated to determine optimal cut-off values between malignant and benign lesions.ResultsTwenty-one of the 98 patients who underwent FNA biopsy or thyroidectomy had malignant disease (21.4%). Malignant lesions had significantly higher thyroid lesion SUVmax, TL/TBG, TL/BP, and TL/L than benign nodules. The receiver operating curves derived cut-off ratio TL/TBG of more than 2.0 differentiated benign from malignant lesions best with a specificity and sensitivity of 0.76 and 0.88, respectively.ConclusionThe incidence of malignancy in biopsied focal hypermetabolic thyroid lesions is 21.4%. Lesions on F-FDG PET/CT studies, with a ratio TL/TBG more than 2.0, warrant further work-up with ultrasound and FNA to exclude malignancy.
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- 2016
84. Variations in PET/MRI Operations: Results from an International Survey Among 39 Active Sites
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Fendler, Wolfgang Peter, Czernin, Johannes, Herrmann, Ken, and Beyer, Thomas
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Biomedical and Clinical Sciences ,Clinical Sciences ,Biomedical Imaging ,Good Health and Well Being ,Humans ,Internationality ,Internet ,Magnetic Resonance Imaging ,Multimodal Imaging ,Positron-Emission Tomography ,Surveys and Questionnaires ,PET/MRI ,survey ,imaging protocols ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
Information has been collected from PET/MRI operational sites to identify its present and future applications. This may help to focus discussions on common interests of the PET/MRI community.MethodsA web-based survey of PET/MRI users was conducted from June to October 2015. The survey was composed of 26 questions related to the PET/MRI center, present use and imaging protocols, and perspectives on key applications.ResultsResponses were collected from 39 international sites that operated PET/MRI for a median of 30 mo (range, 2-62 mo). Most installations were located in public institutions with an academic focus (n = 26, 67%). Systems were primarily operated by nuclear medicine departments (n = 13, 33%), jointly by nuclear medicine and radiology (n = 11, 28%), and radiology only (n = 10, 26%). PET/MRI operation was equally focused on clinic routine and research (47% vs. 45% of sites, respectively). Sites reported a strong focus on oncology (76% of research and 88% of clinical applications). Other applications included neurology (9% clinical, 12% research) and cardiology (3% clinical, 6% research). Perceived superiority over PET/CT was identified as the strongest driver for clinical adoption. Over half the operators expect PET/MRI to excel in clinical routine within 3-5 y. Emerging key applications for future PET/MRI use were cardiovascular disease and imaging of inflammation.ConclusionAn international survey of early PET/MR adopters reveals a mixed use of this combined imaging modality, with a focus on oncology. The future of PET/MRI is seen in expanded application for oncology and neurology, but also cardiovascular disease and inflammation.
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- 2016
85. Synthesis and preclinical evaluation of an Al18F radiofluorinated GLU-UREA-LYS(AHX)-HBED-CC PSMA ligand
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Boschi, Stefano, Lee, Jason T, Beykan, Seval, Slavik, Roger, Wei, Liu, Spick, Claudio, Eberlein, Uta, Buck, Andreas K, Lodi, Filippo, Cicoria, Gianfranco, Czernin, Johannes, Lassmann, Michael, Fanti, Stefano, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Cancer ,Bioengineering ,Animals ,Antigens ,Surface ,Biomarkers ,Tumor ,Cell Line ,Tumor ,Drug Evaluation ,Preclinical ,Edetic Acid ,Fluorine Radioisotopes ,Gallium Isotopes ,Gallium Radioisotopes ,Glutamate Carboxypeptidase II ,Isotope Labeling ,Male ,Metabolic Clearance Rate ,Mice ,Mice ,Inbred C57BL ,Oligopeptides ,Organ Specificity ,Organometallic Compounds ,Positron-Emission Tomography ,Prostatic Neoplasms ,Radiation Dosage ,Radiation Exposure ,Radiopharmaceuticals ,Reproducibility of Results ,Sensitivity and Specificity ,Tissue Distribution ,Whole-Body Counting ,PET ,PSMA ,F-18 ,Dosimetry ,Preclinical ,Prostate cancer ,18F ,Other Physical Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
PurposeThe aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.MethodsSeveral conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed.ResultsQuantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p
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- 2016
86. 68Ga-PSMA-PET/CT in Patients With Biochemical Prostate Cancer Recurrence and Negative 18F-Choline-PET/CT
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Bluemel, Christina, Krebs, Markus, Polat, Bülent, Linke, Fränze, Eiber, Matthias, Samnick, Samuel, Lapa, Constantin, Lassmann, Michael, Riedmiller, Hubertus, Czernin, Johannes, Rubello, Domenico, Bley, Thorsten, Kropf, Saskia, Wester, Hans-Juergen, Buck, Andreas K, and Herrmann, Ken
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Bioengineering ,Prostate Cancer ,Clinical Research ,Urologic Diseases ,Biomedical Imaging ,Cancer ,Aged ,Aged ,80 and over ,Antigens ,Surface ,Choline ,Gallium Radioisotopes ,Glutamate Carboxypeptidase II ,Humans ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Positron Emission Tomography Computed Tomography ,Prostatic Neoplasms ,choline-PET/CT ,PSMA-PET/CT ,prostate cancer ,recurrence ,restaging ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
PurposeInvestigating the value of Ga-PSMA-PET/CT in biochemically recurring prostate cancer patients with negative F-choline-PET/CT.Patients and methodsOne hundred thirty-nine consecutive patients with biochemical recurrence after curative (surgery and/or radiotherapy) therapy were offered participation in this sequential clinical imaging approach. Patients first underwent an F-choline-PET/CT. If negative, an additional Ga-PSMA-PET/CT was offered. One hundred twenty-five of 139 eligible patients were included in the study; 32 patients underwent additional Ga-PSMA-PET/CT. Patients with equivocal findings (n = 5) on F-choline-PET/CT and those who declined the additional Ga-PSMA-PET/CT (n = 9) were excluded. Images were analyzed visually for the presence of suspicious lesions. Findings on PET/CT were correlated with PSA level, PSA doubling time (dt), and PSA velocity (vel).ResultsThe overall detection rates were 85.6% (107/125) for the sequential imaging approach and 74.4% (93/125) for F-choline-PET/CT alone. Ga-PSMA-PET/CT detected sites of recurrence in 43.8% (14/32) of the choline-negative patients. Detection rates of the sequential imaging approach and F-choline-PET/CT alone increased with higher serum PSA levels and PSA vel. Subgroup analysis of Ga-PSMA-PET/CT in F-choline negative patients revealed detection rates of 28.6%, 45.5%, and 71.4% for PSA levels of 0.2 or greater to less than 1 ng/mL, 1 to 2 ng/mL, and greater than 2 ng/mL, respectively.ConclusionsThe sequential imaging approach designed to limit Ga-PSMA imaging to patients with negative choline scans resulted in high detection rates. Ga-PSMA-PET/CT identified sites of recurrent disease in 43.8% of the patients with negative F-choline PET/CT scans.
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- 2016
87. [18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity
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Kim, Woosuk, Le, Thuc M, Wei, Liu, Poddar, Soumya, Bazzy, Jimmy, Wang, Xuemeng, Uong, Nhu T, Abt, Evan R, Capri, Joseph R, Austin, Wayne R, Van Valkenburgh, Juno S, Steele, Dalton, Gipson, Raymond M, Slavik, Roger, Cabebe, Anthony E, Taechariyakul, Thotsophon, Yaghoubi, Shahriar S, Lee, Jason T, Sadeghi, Saman, Lavie, Arnon, Faull, Kym F, Witte, Owen N, Donahue, Timothy R, Phelps, Michael E, Herschman, Harvey R, Herrmann, Ken, Czernin, Johannes, and Radu, Caius G
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Orphan Drug ,Cancer ,Rare Diseases ,Hematology ,Adenine Nucleotides ,Animals ,Antineoplastic Agents ,Arabinonucleosides ,Biomarkers ,Tumor ,Cell Line ,Tumor ,Clofarabine ,Contrast Media ,Deoxycytidine Kinase ,Humans ,Leukemia ,Mice ,Neoplasms ,Positron-Emission Tomography ,Prodrugs ,Rats ,nucleotide metabolism ,deoxycytidine kinase ,PET imaging ,cancer - Abstract
Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.
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- 2016
88. A Study on the Basic Criteria for Selecting Heterogeneity Parameters of F18-FDG PET Images
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Forgacs, Attila, Jonsson, Hermann Pall, Dahlbom, Magnus, Daver, Freddie, DiFranco, Matthew D, Opposits, Gabor, Krizsan, Aron K, Garai, Ildiko, Czernin, Johannes, Varga, Jozsef, Tron, Lajos, and Balkay, Laszlo
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Cancer ,Fluorodeoxyglucose F18 ,Humans ,Lung ,Lung Neoplasms ,Phantoms ,Imaging ,Positron Emission Tomography Computed Tomography ,Radiopharmaceuticals ,Reproducibility of Results ,Retrospective Studies ,Tumor Burden ,General Science & Technology - Abstract
Textural analysis might give new insights into the quantitative characterization of metabolically active tumors. More than thirty textural parameters have been investigated in former F18-FDG studies already. The purpose of the paper is to declare basic requirements as a selection strategy to identify the most appropriate heterogeneity parameters to measure textural features. Our predefined requirements were: a reliable heterogeneity parameter has to be volume independent, reproducible, and suitable for expressing quantitatively the degree of heterogeneity. Based on this criteria, we compared various suggested measures of homogeneity. A homogeneous cylindrical phantom was measured on three different PET/CT scanners using the commonly used protocol. In addition, a custom-made inhomogeneous tumor insert placed into the NEMA image quality phantom was imaged with a set of acquisition times and several different reconstruction protocols. PET data of 65 patients with proven lung lesions were retrospectively analyzed as well. Four heterogeneity parameters out of 27 were found as the most attractive ones to characterize the textural properties of metabolically active tumors in FDG PET images. These four parameters included Entropy, Contrast, Correlation, and Coefficient of Variation. These parameters were independent of delineated tumor volume (bigger than 25-30 ml), provided reproducible values (relative standard deviation< 10%), and showed high sensitivity to changes in heterogeneity. Phantom measurements are a viable way to test the reliability of heterogeneity parameters that would be of interest to nuclear imaging clinicians.
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- 2016
89. Characterizing Normal Variant [68Ga]Ga-FAPI-46 Uptake in the Epididymis
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Maliha, Peter George, primary, Hotta, Masatoshi, additional, Czernin, Johannes, additional, and Calais, Jeremie, additional
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- 2023
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90. Advancing Nuclear Medicine at the Multiomics Intersection
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Kairemo, Kalevi, primary and Czernin, Johannes, additional
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- 2023
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91. Tandem Isotope Therapy with225Ac- and177Lu-PSMA-617 in a Murine Model of Prostate Cancer
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Meyer, Catherine, primary, Stuparu, Andreea, additional, Lueckerath, Katharina, additional, Calais, Jeremie, additional, Czernin, Johannes, additional, Slavik, Roger, additional, and Dahlbom, Magnus, additional
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- 2023
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92. Pioneering Research on Cancer Quality of Life and Outcomes
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Ganz, Patricia A., primary and Czernin, Johannes, additional
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- 2023
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93. A Tribute to OurJNMAssociate Editors
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Czernin, Johannes, primary
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- 2023
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94. Illuminating Cardiac Function: Heinz Schelbert Talks with Heiko Schöder and Johannes Czernin About a Pioneering Career in Nuclear Cardiology.
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Schelbert, Heinrich, Schöder, Heiko, and Czernin, Johannes
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- 2024
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95. Inventing His Own Career Path: Freek Beekman Talks with Johannes Czernin and Christine Mona About Success in Academia and Industry.
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Beekman, Freek, Czernin, Johannes, and Mona, Christine
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- 2024
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96. Dosimetry, biodistribution, and safety of flurpiridaz F 18 in healthy subjects undergoing rest and exercise or pharmacological stress PET myocardial perfusion imaging
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Maddahi, Jamshid, Bengel, Frank, Czernin, Johannes, Crane, Paul, Dahlbom, Magnus, Schelbert, Heinrich, Sparks, Richard, Phelps, Michael, and Lazewatsky, Joel
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- 2019
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97. Transforming an Academic Radiochemistry Facility for Positron Emission Tomography Drug cGMP Compliance
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Zhu, Shaojun, Mosessian, Sherly, Kroeger, Kurt, Sadeghi, Saman, Slavik, Roger, Kinloch, Simon, Moore, Melissa, Allen-Auerbach, Martin, Czernin, Johannes, and Phelps, Michael
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- 2020
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98. Relationship Between [18F]FDOPA PET Uptake, Apparent Diffusion Coefficient (ADC), and Proliferation Rate in Recurrent Malignant Gliomas.
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Karavaeva, Elena, Harris, Robert J, Leu, Kevin, Shabihkhani, Maryam, Yong, William H, Pope, Whitney B, Lai, Albert, Nghiemphu, Phioanh L, Liau, Linda M, Chen, Wei, Czernin, Johannes, Cloughesy, Timothy F, and Ellingson, Benjamin M
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Humans ,Glioma ,Brain Neoplasms ,Neoplasm Recurrence ,Local ,Inflammation ,Dihydroxyphenylalanine ,Ki-67 Antigen ,Contrast Media ,Positron-Emission Tomography ,Magnetic Resonance Imaging ,Mitotic Index ,Immunohistochemistry ,Retrospective Studies ,Mitosis ,Cell Proliferation ,Diffusion ,Image Processing ,Computer-Assisted ,Adult ,Aged ,Middle Aged ,Female ,Male ,Young Adult ,Brain Cancer ,Cancer ,Clinical Research ,Rare Diseases ,Biomedical Imaging ,Brain Disorders ,Diffusion MRI ,[F-18]FDOPA PET ,Malignant glioma ,Proliferation ,ADC ,Physiology ,Clinical Sciences ,Nuclear Medicine & Medical Imaging - Abstract
PurposeDiffusion magnetic resonance imaging (MRI) and 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) positron emission tomography (PET) are used to interrogate malignant tumor microenvironment. It remains unclear whether there is a relationship between [(18)F]FDOPA uptake, diffusion MRI estimates of apparent diffusion coefficient (ADC), and mitotic activity in the context of recurrent malignant gliomas, where the tumor may be confounded by the effects of therapy. The purpose of the current study is to determine whether there is a correlation between these imaging techniques and mitotic activity in malignant gliomas.ProceduresWe retrospectively examined 29 patients with recurrent malignant gliomas who underwent structural MRI, diffusion MRI, and [(18)F]FDOPA PET prior to surgical resection. Qualitative associations were noted, and quantitative voxel-wise and median measurement correlations between [(18)F]FDOPA PET, ADC, and mitotic index were performed.ResultsAreas of high [(18)F]FDOPA uptake exhibited low ADC and areas of hyperintensity T2/fluid-attenuated inversion recovery (FLAIR) with low [(18)F]FDOPA uptake exhibited high ADC. There was a significant inverse voxel-wise correlation between [(18)F]FDOPA and ADC for all patients. Median [(18)F]FDOPA uptake and median ADC also showed a significant inverse correlation. Median [(18)F]FDOPA uptake was positively correlated, and median ADC was inversely correlated with mitotic index from resected tumor tissue.ConclusionsA significant association may exist between [(18)F]FDOPA uptake, diffusion MRI, and mitotic activity in recurrent malignant gliomas.
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- 2015
99. Biodistribution and Radiation Dosimetry for a Probe Targeting Prostate-Specific Membrane Antigen for Imaging and Therapy
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Herrmann, Ken, Bluemel, Christina, Weineisen, Martina, Schottelius, Margret, Wester, Hans-Jürgen, Czernin, Johannes, Eberlein, Uta, Beykan, Seval, Lapa, Constantin, Riedmiller, Hubertus, Krebs, Markus, Kropf, Saskia, Schirbel, Andreas, Buck, Andreas K, and Lassmann, Michael
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Prostate Cancer ,Urologic Diseases ,Biomedical Imaging ,Bioengineering ,Cancer ,Aged ,Antigens ,Surface ,Bone Marrow ,Edetic Acid ,Gallium Isotopes ,Gallium Radioisotopes ,Glutamate Carboxypeptidase II ,Humans ,Kidney ,Male ,Middle Aged ,Oligopeptides ,Positron-Emission Tomography ,Prostatic Neoplasms ,Radiometry ,Radiopharmaceuticals ,Salivary Glands ,Spleen ,Tissue Distribution ,Whole Body Imaging ,PET ,PSMA ,Ga-68 ,dosimetry ,prostate cancer ,68Ga ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
UnlabelledProstate-specific membrane antigen (PSMA) is a promising target for diagnosis and treatment of prostate cancer. EuK-Subkff-(68)Ga-DOTAGA ((68)Ga-PSMA Imaging & Therapy [PSMA I&T]) is a recently introduced PET tracer for imaging PSMA expression in vivo. Whole-body distribution and radiation dosimetry of this new probe were evaluated.MethodsFive patients with a history of prostate cancer were injected intravenously with 91-148 MBq of (68)Ga-PSMA I&T (mean ± SD, 128 ± 23 MBq). After an initial series of rapid whole-body scans, 3 static whole-body scans were acquired at 1, 2, and 4 h after tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM.ResultsInjection of 150 MBq of (68)Ga-PSMA I&T resulted in an effective dose of 3.0 mSv. The kidneys were the critical organ (33 mGy), followed by the urinary bladder wall and spleen (10 mGy each), salivary glands (9 mGy each), and liver (7 mGy).Conclusion(68)Ga-PSMA I&T exhibits a favorable dosimetry, delivering organ doses that are comparable to (kidneys) or lower than those delivered by (18)F-FDG.
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- 2015
100. Impact of 68Ga-DOTATATE PET/CT on the Management of Neuroendocrine Tumors: The Referring Physician's Perspective
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Herrmann, Ken, Czernin, Johannes, Wolin, Edward M, Gupta, Pawan, Barrio, Martin, Gutierrez, Antonio, Schiepers, Christiaan, Mosessian, Sherly, Phelps, Michael E, and Allen-Auerbach, Martin S
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Biomedical Imaging ,Cancer ,Neurosciences ,Adult ,Aged ,Aged ,80 and over ,Female ,Humans ,Image Interpretation ,Computer-Assisted ,Male ,Middle Aged ,Multimodal Imaging ,Neoplasm Metastasis ,Neuroendocrine Tumors ,Organometallic Compounds ,Physicians ,Positron-Emission Tomography ,Referral and Consultation ,Research Report ,Surveys and Questionnaires ,Tomography ,X-Ray Computed ,NET ,neuroendocrine tumors ,somatostatin receptor ,PET ,DOTATATE ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
UnlabelledSomatostatin receptor imaging with (68)Ga-DOTATATE PET/CT (DOTATATE) is increasingly used for managing patients with neuroendocrine tumors. The objective of this study was to determine referring physicians' perspectives on the impact of DOTATATE on the management of neuroendocrine tumors.MethodsA set of 2 questionnaires (pre-PET and post-PET) was sent to the referring physicians of 100 consecutive patients with known or suspected neuroendocrine tumors, who were evaluated with DOTATATE. Questionnaires on 88 patients were returned (response rate, 88%). Referring physicians categorized the DOTATATE findings on the basis of the written PET reports as negative, positive, or equivocal for disease. The likelihood for metastatic disease was scored as low, moderate, or high. The intended management before and changes as a consequence of the PET study were indicated.ResultsThe indications for PET/CT were initial and subsequent treatment strategy assessments in 14% and 86% of patients, respectively. Referring physicians reported that DOTATATE led to a change in suspicion for metastatic disease in 21 patients (24%; increased and decreased suspicion in 9 [10%] and 12 [14%] patients, respectively). Intended management changes were reported in 53 of 88 (60%) patients. Twenty patients (23%) scheduled to undergo chemotherapy were switched to treatments without chemotherapy, and 6 (7%) were switched from watch-and-wait to other treatment strategies. Conversely, 5 patients (6%) were switched from their initial treatment strategy to watch-and-wait.ConclusionThis survey of referring physicians demonstrates a substantial impact of DOTATATE on the intended management of patients with neuroendocrine tumors.
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- 2015
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