Dynamic PET-MRI for integrated quantification of molecular immune responses and their vascular consequences

Principal investigators: Philipp Backhaus, Florian Büther
Project number: CRC 1450 B06
Project term: 01/2021–12/2024

Graphical abstract
© CRC inSight

The aim of the project is to elaborate synergistic links between PET and MRI in a hybrid PET-MRI system by dual dynamic recordings of arterial input functions and pharmacokinetic modelling (1). A framework to deduce the PET arterial input function from MRI will be established by performing simultaneous recordings in animals, and finally tested in patient scans (2, 3).

Building on this, approaches will be evaluated to integrate MRI-derived information on perfusion and permeability into PET modelling in mouse models of ischemia driven inflammation in the heart and kidney (4) to uncover and better understand unspecific radiotracer uptake phenomena (5, 6).

Novel DCE-MRI setup (A) for extracorporeal measurements of PET/MRI arterial input function (AIF) in mice, including two reservoirs for determination of DCE-MRI AIFs and a radiation detector for radiotracer AIFs. Corresponding maximum-intensity-projections (MIPs) of an exemplary DCE-MRI scan at different timepoints after injection [s] (B). This method allows us to quantitatively detect changes in the perfusion of glioblastoma in mice using DCE-MRI images (C) and thus improving clinical decision making in terms of diagnosis and treatment. The accuracy of our method is finally cross-validated with autoradiography (left) and LA-ICP-MS (right) in cooperation with project B02 (D).
© Florian Gierse M.D. candidate / research group Michael Schäfers; project head Florian Büther and Philipp Backhaus; LA-ICP-MS analysis provided by Katharina Kronenberg / research group Uwe Karst

Team

Principal investigators

Project members

Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.

2023

Cufe J, Gierse F, Schafers KP, Hermann S, Schafers MA, Backhaus P, Buther F. Dispersion-corrected extracorporeal arterial input functions in PET studies of mice: a comparison to intracorporeal microprobe measurements. EJNMMI Res 2023;13: 86. Abstract
Galbiati A, Dorten P, Gilardoni E, Gierse F, Bocci M, Zana A, Mock J, Claesener M, Cufe J, Buther F, Schafers K, Hermann S, Schafers M, Neri D, Cazzamalli S, Backhaus P. Tumor-Targeted Interleukin 2 Boosts the Anticancer Activity of FAP-Directed Radioligand Therapeutics. J Nucl Med 2023Abstract

2022

Backhaus P, Burg MC, Asmus I, Pixberg M, Buther F, Breyholz H-J, Yeh R, Weigel SB, Stichling P, Heindel W, Bobe S, Barth P, Tio J, Schafers M. Initial Results of FAPI-PET/MRI to Assess Response to Neoadjuvant Chemotherapy in Breast Cancer. J Nucl Med 2022Abstract
Backhaus P, Burg MC, Roll W, Buther F, Breyholz H-J, Weigel S, Heindel W, Pixberg M, Barth P, Tio J, Schafers M. Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer. Radiology 2022;302: 39-47. Abstract
Backhaus P, Gierse F, Burg MC, Buther F, Asmus I, Dorten P, Cufe J, Roll W, Neri D, Cazzamalli S, Millul J, Mock J, Galbiati A, Zana A, Schafers KP, Hermann S, Weckesser M, Tio J, Wagner S, Breyholz H-J, Schafers M. Translational imaging of the fibroblast activation protein (FAP) using the new ligand [(68)Ga]Ga-OncoFAP-DOTAGA. Eur J Nucl Med Mol Imaging 2022;49: 1822-1832. Abstract
Zana A, Galbiati A, Gilardoni E, Bocci M, Millul J, Sturm T, Stucchi R, Elsayed A, Nadal L, Cirillo M, Roll W, Stegger L, Asmus I, Backhaus P, Schaefers M, Neri D, Cazzamalli S. Fibroblast Activation Protein triggers release of drug payload from non-internalizing small molecule-drug conjugates in solid tumors. Clin Cancer Res 2022Abstract

2020

Backhaus P, Buther F, Wachsmuth L, Frohwein L, Buchholz R, Karst U, Schafers K, Hermann S, Schafers M, Faber C. Toward precise arterial input functions derived from DCE-MRI through a novel extracorporeal circulation approach in mice. Magn Reson Med 2020;84: 1404-1415. Abstract
Backhaus P, Roll W, Beuker C, Zinnhardt B, Seifert R, Wenning C, Eisenblatter M, Thomas C, Schmidt-Pogoda A, Strunk D, Wagner S, Faust A, Tuttelmann F, Ropke A, Jacobs AH, Stummer W, Wiendl H, Meuth SG, Schafers M, Grauer O, Minnerup J. Initial experience with [(18)F]DPA-714 TSPO-PET to image inflammation in primary angiitis of the central nervous system. Eur J Nucl Med Mol Imaging 2020Abstract
Buther F, Jones J, Seifert R, Stegger L, Schleyer P, Schafers M. Clinical Evaluation of a Data-Driven Respiratory Gating Algorithm for Whole-Body PET with Continuous Bed Motion. J Nucl Med 2020;61: 1520-1527. Abstract
Foray C, Barca C, Backhaus P, Schelhaas S, Winkeler A, Viel T, Schafers M, Grauer O, Jacobs AH, Zinnhardt B. Multimodal Molecular Imaging of the Tumour Microenvironment. Adv Exp Med Biol 2020;1225: 71-87. Abstract
Zinnhardt B, Muther M, Roll W, Backhaus P, Jeibmann A, Foray C, Barca C, Doring C, Tavitian B, Dolle F, Weckesser M, Winkeler A, Hermann S, Wagner S, Wiendl H, Stummer W, Jacobs AH, Schafers M, Grauer OM. TSPO imaging-guided characterization of the immunosuppressive myeloid tumor microenvironment in patients with malignant glioma. Neuro Oncol 2020;22: 1030-1043. Abstract

2018

Backhaus P, Noto B, Avramovic N, Grubert LS, Huss S, Bogemann M, Stegger L, Weckesser M, Schafers M, Rahbar K. Targeting PSMA by radioligands in non-prostate disease-current status and future perspectives. Eur J Nucl Med Mol Imaging 2018;45: 860-877. Abstract
Büther F, Ernst I, Frohwein LJ, Pouw J, Schafers KP, Stegger L. Data-driven gating in PET: Influence of respiratory signal noise on motion resolution. Med Phys 2018;45: 3205-3213. Abstract

2017

Noto B, Buther F, Auf der Springe K, Avramovic N, Heindel W, Schafers M, Allkemper T, Stegger L. Impact of PET acquisition durations on image quality and lesion detectability in whole-body 68Ga-PSMA PET-MRI. EJNMMI Res 2017;7: 12. Abstract