@article{BluemelLinkeHerrmannetal.2016, author = {Bluemel, Christina and Linke, Fraenze and Herrmann, Ken and Simunovic, Iva and Eiber, Matthias and Kestler, Christian and Buck, Andreas K. and Schirbel, Andreas and Bley, Thorsten A. and Wester, Hans-Juergen and Vergho, Daniel and Becker, Axel}, title = {Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy}, series = {EJNMMI Research}, volume = {6}, journal = {EJNMMI Research}, number = {78}, doi = {10.1186/s13550-016-0233-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147798}, year = {2016}, abstract = {Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 \%) patients. In 62.5 \% of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 \%) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 \%) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 \%) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 \% of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT.}, language = {en} } @article{HerrmannBuckSchusteretal.2014, author = {Herrmann, Ken and Buck, Andreas K. and Schuster, Tibor and Abbrederis, Kathrin and Bl{\"u}mel, Christina and Santi, Ivan and Rudelius, Martina and Wester, Hans-J{\"u}rgen and Peschel, Christian and Schwaiger, Markus and Dechow, Tobias and Keller, Ulrich}, title = {Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL}, series = {Oncotarget}, volume = {5}, journal = {Oncotarget}, number = {12}, issn = {1949-2553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120659}, pages = {4050-59}, year = {2014}, abstract = {Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.}, language = {en} } @article{GrafLiHerrmannetal.2014, author = {Graf, Nicolas and Li, Zhoulei and Herrmann, Ken and Weh, Daniel and Aichler, Michaela and Slawska, Jolanta and Walch, Axel and Peschel, Christian and Schwaiger, Markus and Buck, Andreas K. and Dechow, Tobias and Keller, Ulrich}, title = {Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma}, series = {Oncotargets and Therapy}, volume = {7}, journal = {Oncotargets and Therapy}, doi = {10.2147/OTT.S59314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117915}, pages = {789-798}, year = {2014}, abstract = {Background: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[F-18] fluorothymidine (FLT). Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy.}, language = {en} } @article{PhilippAbbrederisHerrmannKnopetal.2015, author = {Philipp-Abbrederis, Kathrin and Herrmann, Ken and Knop, Stefan and Schottelius, Margret and Eiber, Matthias and L{\"u}ckerath, Katharina and Pietschmann, Elke and Habringer, Stefan and Gerngroß, Carlos and Franke, Katharina and Rudelius, Martina and Schirbel, Andreas and Lapa, Constantin and Schwamborn, Kristina and Steidle, Sabine and Hartmann, Elena and Rosenwald, Andreas and Kropf, Saskia and Beer, Ambros J and Peschel, Christian and Einsele, Hermann and Buck, Andreas K and Schwaiger, Markus and G{\"o}tze, Katharina and Wester, Hans-J{\"u}rgen and Keller, Ulrich}, title = {In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma}, series = {EMBO Molecular Medicine}, volume = {7}, journal = {EMBO Molecular Medicine}, number = {4}, doi = {10.15252/emmm.201404698}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148738}, pages = {477-487}, year = {2015}, abstract = {CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.}, language = {en} }