TY - JOUR A1 - Hecht, Markus A1 - Erber, Sonja A1 - Harrer, Thomas A1 - Klinker, Hartwig A1 - Roth, Thomas A1 - Parsch, Hans A1 - Fiebig, Nora A1 - Fietkau, Rainer A1 - Distel, Luitpold V. T1 - Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells JF - PLoS ONE N2 - Background Cancer prevention and therapy in HIV-1-infected patients will play an important role in future. The non-nucleoside reverse transcriptase inhibitors (NNRTI) Efavirenz and Nevirapine are cytotoxic against cancer cells in vitro. As other NNRTIs have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo. Methods Cytotoxicity was studied by Annexin-V-APC/7AAD staining and flow cytometry in the pancreatic cancer cell lines BxPC-3 and Panc-1 and confirmed by colony formation assays. The 50% effective cytotoxic concentrations (EC50) were calculated and compared to the blood levels in our patients and published data. Results The in vitro EC50 of the different drugs in the BxPC-3 pancreatic cancer cells were: Efavirenz 31.5\(\mu\)mol/l (= 9944ng/ml), Nevirapine 239\(\mu\)mol/l (= 63786ng/ml), Etravirine 89.0\(\mu\)mol/l (= 38740ng/ml), Lersivirine 543\(\mu\)mol/l (= 168523ng/ml), Delavirdine 171\(\mu\)mol/l (= 78072ng/ml), Rilpivirine 24.4\(\mu\)mol/l (= 8941ng/ml). As Efavirenz and Rilpivirine had the highest cytotoxic potential and Nevirapine is frequently used in HIV-1 positive patients, the results of these three drugs were further studied in Panc-1 pancreatic cancer cells and confirmed with colony formation assays. 205 patient blood levels of Efavirenz, 127 of Rilpivirine and 31 of Nevirapine were analyzed. The mean blood level of Efavirenz was 3587ng/ml (range 162-15363ng/ml), of Rilpivirine 144ng/ml (range 0-572ng/ml) and of Nevirapine 4955ng/ml (range 1856-8697ng/ml). Blood levels from our patients and from published data had comparable Efavirenz levels to the in vitro toxic EC50 in about 1 to 5% of all patients. Conclusion All studied NNRTIs were toxic against cancer cells. A low percentage of patients taking Efavirenz reached in vitro cytotoxic blood levels. It can be speculated that in HIV-1 positive patients having high Efavirenz blood levels pancreatic cancer incidence might be reduced. Efavirenz might be a new option in the treatment of cancer. KW - human hepatic cells KW - active antiretroviral therapy KW - differentiated thyroid tumor KW - HIV-infected patients KW - pharmacokinetic interaction KW - LINE-1 retrotransposition KW - HIV-1-infected subjects KW - healthy volunteers KW - prostate cancer KW - i-131 uptake Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151694 VL - 10 IS - 6 ER - TY - JOUR A1 - Pinkawa, Michael A1 - Aebersold, Daniel M. A1 - Böhmer, Dirk A1 - Flentje, Michael A1 - Ghadjar, Pirus A1 - Schmidt-Hegemann, Nina-Sophie A1 - Höcht, Stefan A1 - Hölscher, Tobias A1 - Müller, Arndt-Christian A1 - Niehoff, Peter A1 - Sedlmayer, Felix A1 - Wolf, Frank A1 - Zamboglou, Constantinos A1 - Zips, Daniel A1 - Wiegel, Thomas T1 - Radiotherapy in nodal oligorecurrent prostate cancer JF - Strahlentherapie und Onkologie N2 - Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations. KW - prostate cancer KW - oligorecurrence KW - metastasis-directed therapy KW - radiation therapy KW - androgen deprivation therapy KW - stereotactic body radiotherapy KW - oligmometastases KW - lymph node metastases Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307763 SN - 0179-7158 SN - 1439-099X VL - 197 IS - 7 ER - TY - INPR A1 - Werner, Rudolf A. A1 - Bundschuh, Ralph A. A1 - Bundschuh, Lena A1 - Fanti, Stefano A1 - Javadi, Mehrbod S. A1 - Higuchi, Takahiro A1 - Weich, A. A1 - Pienta, Kenneth J. A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Herrmann, Ken A1 - Lapa, Constantin A1 - Rowe, Steven P. T1 - Novel Structured Reporting Systems for Theranostic Radiotracers T2 - Journal of Nuclear Medicine N2 - Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET will be briefly introduced followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed. KW - standardized reporting KW - Positronen-Emissions-Tomografie KW - prostate cancer KW - neuroendocrine neoplasia KW - 68Ga-DOTATATE KW - 68Ga-DOTATOC KW - 68Ga-DOTANOC KW - somatostatin receptor KW - SSTR KW - prostate-specific membrane antigen KW - PSMA KW - RADS KW - PSMA-RADS KW - SSTR-RADS KW - MI-RADS KW - PROMISE Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174629 SN - 0161-5505 N1 - This research was originally published in JNM. Authors: Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Stefano Fanti, Mehrbod S. Javadi, Takahiro Higuchi, A. Weich, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Ken Herrmann, Constantin Lapa, Steven P. Rowe. Novel Structured Reporting Systems for Theranostic Radiotracers. J Nucl Med May 1, 2019 vol. 60 no. 5 577-584 © SNMMI. ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Bundschuh, Ralph A. A1 - Bundschuh, Lena A1 - Javadi, Mehrbod S. A1 - Higuchi, Takahiro A1 - Weich, Alexander A1 - Sheikhbahaei, Sara A1 - Pienta, Kenneth J. A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Lapa, Constantin A1 - Rowe, Steven P. T1 - MI-RADS: Molecular Imaging Reporting and Data Systems – A Generalizable Framework for Targeted Radiotracers with Theranostic Implications JF - Annals of Nuclear Medicine N2 - Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems. KW - PET KW - Positronen-Emissions-Tomografie KW - prostate cancer KW - neuroendocrine tumor KW - prostate-specific membrane antigen (PSMA) KW - somatostatin receptor (SSTR) KW - positron emission tomography KW - theranostics KW - standardization KW - RADS KW - reporting and data systems KW - personalized medicine Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166995 SN - 0914-7187 ER -