@article{ZhouDierksKertelsetal.2020, author = {Zhou, Xiang and Dierks, Alexander and Kertels, Olivia and Samnick, Samuel and Kircher, Malte and Buck, Andreas K. and Haertle, Larissa and Knorz, Sebastian and B{\"o}ckle, David and Scheller, Lukas and Messerschmidt, Janin and Barakat, Mohammad and Truger, Marietta and Haferlach, Claudia and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, K. Martin and Lapa, Constantin}, title = {The link between cytogenetics/genomics and imaging patterns of relapse and progression in patients with relapsed/refractory multiple myeloma: a pilot study utilizing 18F-FDG PET/CT}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {9}, issn = {2072-6694}, doi = {10.3390/cancers12092399}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211157}, year = {2020}, abstract = {Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1-10) lines of therapy. Six (25\%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point.}, language = {en} } @article{HeinzeSchirbelNannenetal.2021, author = {Heinze, Britta and Schirbel, Andreas and Nannen, Lukas and Michelmann, David and Hartrampf, Philipp E. and Bluemel, Christina and Schneider, Magdalena and Herrmann, Ken and Haenscheid, Heribert and Fassnacht, Martin and Buck, Andreas K. and Hahner, Stefanie}, title = {Novel CYP11B-ligand [\(^{123/131}\)I]IMAZA as promising theranostic tool for adrenocortical tumors: comprehensive preclinical characterization and first clinical experience}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {49}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {1}, issn = {1619-7089}, doi = {10.1007/s00259-021-05477-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265606}, pages = {301-310}, year = {2021}, abstract = {Purpose Adrenal tumors represent a diagnostic and therapeutic challenge. Promising results have been obtained through targeting the cytochrome P450 enzymes CYP11B1 and CYP11B2 for molecular imaging, and [\(^{123/131}\)I]iodometomidate ([\(^{123/131}\)I]IMTO) has even been successfully introduced as a theranostic agent. As this radiopharmaceutical shows rapid metabolic inactivation, we aimed at developing new improved tracers. Methods Several IMTO derivatives were newly designed by replacing the unstable methyl ester by different carboxylic esters or amides. The inhibition of aldosterone and cortisol synthesis was tested in different adrenocortical cell lines. The corresponding radiolabeled compounds were assessed regarding their stability, in vitro cell uptake, in vivo biodistribution in mice, and their binding specificity to cryosections of human adrenocortical and non-adrenocortical tissue. Furthermore, a first investigation was performed in patients with known metastatic adrenal cancer using both [\(^{123}\)I]IMTO and the most promising compound (R)-1-[1-(4-[\(^{123/}\)I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide ([\(^{123}\)I]IMAZA) for scintigraphy. Subsequently, a first endoradiotherapy with [\(^{131}\)I]IMAZA in one of these patients was performed. Results We identified three analogues to IMTO with high-affinity binding to the target enzymes and comparable or higher metabolic stability and very high and specific accumulation in adrenocortical cells in vitro and in vivo. Labeled IMAZA exhibited superior pharmacokinetic and imaging properties compared to IMTO in mice and 3 patients, too. An endoradiotherapy with [\(^{131}\)I]IMAZA induced a 21-month progression-free interval in a patient with rapidly progressing ACC prior this therapy. Conclusion We developed the new radiopharmaceutical [\(^{123/131}\)I]IMAZA with superior properties compared to the reference compound IMTO and promising first experiences in humans.}, language = {en} } @article{HaggeMuellerBirkemoeetal.2021, author = {Hagge, Jonas and M{\"u}ller, J{\"o}rg and Birkemoe, Tone and Buse, J{\"o}rn and Christensen, Rune Haubo Bojesen and Gossner, Martin M. and Gruppe, Axel and Heibl, Christoph and Jarzabek-M{\"u}ller, Andrea and Seibold, Sebastian and Siitonen, Juha and Soutinho, Jo{\~a}o Gon{\c{c}}alo and Sverdrup-Thygeson, Anne and Thorn, Simon and Drag, Lukas}, title = {What does a threatened saproxylic beetle look like? Modelling extinction risk using a new morphological trait database}, series = {Journal of Animal Ecology}, volume = {90}, journal = {Journal of Animal Ecology}, number = {8}, doi = {10.1111/1365-2656.13512}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244717}, pages = {1934 -- 1947}, year = {2021}, abstract = {The extinction of species is a non-random process, and understanding why some species are more likely to go extinct than others is critical for conservation efforts. Functional trait-based approaches offer a promising tool to achieve this goal. In forests, deadwood-dependent (saproxylic) beetles comprise a major part of threatened species, but analyses of their extinction risk have been hindered by the availability of suitable morphological traits. To better understand the mechanisms underlying extinction in insects, we investigated the relationships between morphological features and the extinction risk of saproxylic beetles. Specifically, we hypothesised that species darker in colour, with a larger and rounder body, a lower mobility, lower sensory perception and more robust mandibles are at higher risk. We first developed a protocol for morphological trait measurements and present a database of 37 traits for 1,157 European saproxylic beetle species. Based on 13 selected, independent traits characterising aspects of colour, body shape, locomotion, sensory perception and foraging, we used a proportional-odds multiple linear mixed-effects model to model the German Red List categories of 744 species as an ordinal index of extinction risk. Six out of 13 traits correlated significantly with extinction risk. Larger species as well as species with a broad and round body had a higher extinction risk than small, slim and flattened species. Species with short wings had a higher extinction risk than those with long wings. On the contrary, extinction risk increased with decreasing wing load and with higher mandibular aspect ratio (shorter and more robust mandibles). Our study provides new insights into how morphological traits, beyond the widely used body size, determine the extinction risk of saproxylic beetles. Moreover, our approach shows that the morphological characteristics of beetles can be comprehensively represented by a selection of 13 traits. We recommend them as a starting point for functional analyses in the rapidly growing field of ecological and conservation studies of deadwood.}, language = {en} }