@article{MarquardtHartrampfKollmannsbergeretal.2023, author = {Marquardt, Andr{\´e} and Hartrampf, Philipp and Kollmannsberger, Philip and Solimando, Antonio G. and Meierjohann, Svenja and K{\"u}bler, Hubert and Bargou, Ralf and Schilling, Bastian and Serfling, Sebastian E. and Buck, Andreas and Werner, Rudolf A. and Lapa, Constantin and Krebs, Markus}, title = {Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers15020392}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-305036}, year = {2023}, abstract = {(1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database — representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.}, language = {en} } @article{HartrampfWeinzierlBucketal.2022, author = {Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Buck, Andreas K. and Rowe, Steven P. and Higuchi, Takahiro and Seitz, Anna Katharina and K{\"u}bler, Hubert and Schirbel, Andreas and Essler, Markus and Bundschuh, Ralph A. and Werner, Rudolf A.}, title = {Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I\&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {49}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {9}, doi = {10.1007/s00259-022-05744-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324581}, pages = {3269-3276}, year = {2022}, abstract = {Background Labelled with lutetium-177, the urea-based small molecules PSMA I\&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I\&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8\%) for [\(^{177}\)Lu]Lu-PSMA I\&T and five (9.1\%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9\%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I\&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.}, language = {en} } @article{LisowskiHartrampfHasenaueretal.2023, author = {Lisowski, Dominik and Hartrampf, Philipp E. and Hasenauer, Natalie and Nickl, Vera and Monoranu, Camelia-Maria and Tamihardja, J{\"o}rg}, title = {Complete loss of E-cadherin expression in a rare case of metastatic malignant meningioma: a case report}, series = {BMC Neurology}, volume = {23}, journal = {BMC Neurology}, doi = {10.1186/s12883-023-03450-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357996}, year = {2023}, abstract = {Background Hematogenous tumor spread of malignant meningiomas occurs very rarely but is associated with very poor prognosis. Case presentation We report an unusual case of a patient with a malignant meningioma who developed multiple metastases in bones, lungs and liver after initial complete resection of the primary tumor. After partial hepatic resection, specimens were histologically analyzed, and a complete loss of E-cadherin adhesion molecules was found. No oncogenic target mutations were found. The patient received a combination of conventional radiotherapy and peptide receptor radionuclide therapy (PRRT). Due to aggressive tumor behavior and rapid spread of metastases, the patient deceased after initiation of treatment. Conclusions E-cadherin downregulation is associated with a higher probability of tumor invasion and distant metastasis formation in malignant meningioma. Up to now, the efficacy of systemic therapy, including PRRT, is very limited in malignant meningioma patients.}, language = {en} } @article{MichalskiSchloetelburgHartrampfetal.2023, author = {Michalski, Kerstin and Schl{\"o}telburg, Wiebke and Hartrampf, Philipp E. and Kosmala, Aleksander and Buck, Andreas K. and Hahner, Stefanie and Schirbel, Andreas}, title = {Radiopharmaceuticals for treatment of adrenocortical carcinoma}, series = {Pharmaceuticals}, volume = {17}, journal = {Pharmaceuticals}, number = {1}, issn = {1424-8247}, doi = {10.3390/ph17010025}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355901}, year = {2023}, abstract = {Adrenocortical carcinoma (ACC) represents a rare tumor entity with limited treatment options and usually rapid tumor progression in case of metastatic disease. As further treatment options are needed and ACC metastases are sensitive to external beam radiation, novel theranostic approaches could complement established therapeutic concepts. Recent developments focus on targeting adrenal cortex-specific enzymes like the theranostic twin [\(^{123/131}\)I]IMAZA that shows a good image quality and a promising therapeutic effect in selected patients. But other established molecular targets in nuclear medicine such as the C-X-C motif chemokine receptor 4 (CXCR4) could possibly enhance the therapeutic regimen as well in a subgroup of patients. The aims of this review are to give an overview of innovative radiopharmaceuticals for the treatment of ACC and to present the different molecular targets, as well as to show future perspectives for further developments since a radiopharmaceutical with a broad application range is still warranted.}, language = {en} }