The Translational Radiopharmaceutical Sciences (TRS) Lab focuses on the design, synthesis and preclinical characterization of novel radiolabeled molecules ("tracers") for non-invasive imaging of various biological processes in the human body. On the one hand, this encompasses our ongoing efforts to further improve theranostic targeting of cancer cells themselves, using complementary targeted imaging agents (labeled with a diagnostic radionuclide) and their therapeutic counterparts (labeled with a therapeutic radionuclide). The main focus of the TRS team, however, is to adapt and advance these technologies for potential application in the immunooncology setting. This includes the identification and validation of novel biomarkers and the development of suitable targeted imaging agents to selectively and systemically visualize, quantify and understand the role of certain immune cell types in the tumor microenvironment. The overarching goal of these efforts is the development of imaging tools for better patient selection for immune therapies in different types of cancers. ...
Antibody-based tracers for imaging distinct cell types in the tumor microenvironment (TME)
With their outstanding target selectivity and excellent binding affinity, radiolabeled full-sized antibodies are highly valuable tools for investigating and validating novel biomarkers markers as potential targets for imaging approaches. In our group, we use site-specifically radiolabeled und thus fully immune-reactive antibodies to identify suitable cell surface markers on immune cells in the TME that may provide relevant information on immune cell infiltration and activation. However, since full-sized antibodies display unfavorable pharmacokinetics for clinical imaging applications, we strive to translate our findings directly to smaller antibody-based protein formats (e.g. diabodies) with improved clearance kinetics. By combining such innovative protein formats (developed by S. Dunn, Hi-TIDe: LAbCore immunoglobulin discovery and engineering) with straightforward radiolabeling approaches we aim at ultimately providing an adaptable, readily expandable PET imaging platform for different targets in the TME.
Peptide-based tracers for TME mapping
Since small synthetic peptides represent exceptionally versatile molecular targeting vectors, combining high affinities for their molecular target with fast, tunable pharmacokinetics, most of our tracer development efforts are directed towards novel peptide-based tracers. The molecular targets we aim to address with these peptidic radiopharmaceuticals encompass immune checkpoints, different chemokine receptors and other immune-cell population specific cell-surface markers with high relevance in the TME. In those different projects, we are particularly interested in tackling the challenge of visualizing small numbers of specific immune cells with (oftentimes) relatively low target expression in the TME – which requires particularly high binding affinity and specifically adapted tracer pharmacokinetics.
Perspectives on translational molecular imaging and therapy: an overview of key questions to be addressed.
van Leeuwen FWB, Schottelius M, Mottaghy FM, (...), Lubberink M, Kramer-Marek G, Oyen WJG
EJNMMI research – 2022 Jun 2
CXCR4 peptide-based fluorescence endoscopy in a mouse model of Barrett’s esophagus.
Marcazzan S, Braz Carvalho MJ, Konrad M, (...), Wang TC, Schottelius M, Quante M
EJNMMI research – 2022 Jan 10
In Vivo Targeting of CXCR4-New Horizons.
Schottelius M, Herrmann K, Lapa C
Cancers – 2021 Nov 25
The role of fluorescent and hybrid tracers in radioguided surgery in urogenital malignancies.
DE Vries HM, Schottelius M, Brouwer OR, Buckle T
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... – 2021 May 31
Novel Peptide-Based PET Probe for Non-invasive Imaging of C-X-C Chemokine Receptor Type 4 (CXCR4) in Tumors.
Trotta AM, Aurilio M, D'Alterio C, (...), Scala S, Schottelius M, Di Maro S
Journal of medicinal chemistry – 2021 Mar 4
PhD, Group Leader, Associate Professor, Department of Nuclear Medicine and Molecular Imaging and Department of Oncology, CHUV & UNIL, Ludwig Adjunct Scientist at the Lausanne Branch of the Ludwig Institute of Cancer Researchmargret.email@example.com
Head of clinical radiopharmacy, Department of Pharmacy, CHUV
Postdoctoral Fellow, UNIL & CHUV
Postdoctoral Fellow, UNIL & CHUV
PhD Student, UNIL & CHUV
Research Associate, UNIL & CHUV
PhD Student, UNIL & CHUV
A new class of PentixaFor- and PentixaTher-based theranostic agents with enhanced CXCR4-targeting efficiency.
Osl T, Schmidt A, Schwaiger M, Schottelius M, Wester HJ
Theranostics – 2020 Jul 9
[99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center.
Werner P, Neumann C, Eiber M, Wester HJ, Schottelius M
EJNMMI research – 2020 May 7
From Theranostics to Immunotheranostics: the Concept.
Schaefer N, Prior JO, Schottelius M
Nuclear medicine and molecular imaging – 2020 Apr 8
Synthesis and Preclinical Characterization of the PSMA-Targeted Hybrid Tracer PSMA-I&F for Nuclear and Fluorescence Imaging of Prostate Cancer.
Schottelius M, Wurzer A, Wissmiller K, (...), Schwaiger M, van Leeuwen FWB, Wester HJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine – 2018 Sep 20
Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics.
Habringer S, Lapa C, Herhaus P, (...), Wester HJ, Grigoleit GU, Keller U
Theranostics – 2018 Jan 1
[177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent.
Schottelius M, Osl T, Poschenrieder A, (...), Keller U, Lassmann M, Wester HJ
Theranostics – 2017 Jun 11
CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed Multiple Myeloma.
Lapa C, Herrmann K, Schirbel A, (...), Einsele H, Wester HJ, Kortüm KM
Theranostics – 2017 Apr 8
Preclinical Evaluation and First Patient Application of 99mTc-PSMA-I&S for SPECT Imaging and Radioguided Surgery in Prostate Cancer.
Robu S, Schottelius M, Eiber M, (...), Gschwend J, Schwaiger M, Wester HJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine – 2016 Sep 15
[(111)In]PSMA-I&T: expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery.
Schottelius M, Wirtz M, Eiber M, Maurer T, Wester HJ
EJNMMI research – 2015 Nov 25
First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease.
Herrmann K, Schottelius M, Lapa C, (...), Einsele H, Wester HJ, Knop S
Journal of nuclear medicine : official publication, Society of Nuclear Medicine – 2015 Nov 12
Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging.
Wester HJ, Keller U, Schottelius M, (...), Rudelius M, Kessler H, Schwaiger M
Theranostics – 2015 Mar 1
Ligands for mapping alphavbeta3-integrin expression in vivo.
Schottelius M, Laufer B, Kessler H, Wester HJ
Accounts of chemical research – 2009 Jul 21
[123I]Mtr-TOCA, a radioiodinated and carbohydrated analogue of octreotide: scintigraphic comparison with [111In]octreotide.
Stahl A, Meisetschläger G, Schottelius M, (...), Wolf I, Scheidhauer K, Schwaiger M
European journal of nuclear medicine and molecular imaging – 2005 Sep 9