Nuklearmedizin 2019; 58(02): 111
DOI: 10.1055/s-0039-1683488
Wissenschaftliches Programm: Leuchtturm-Sitzungen
Leuchtturm-Sitzung 6: Translationale Bildgebung
Georg Thieme Verlag KG Stuttgart · New York

Translational immunoPET/MR imaging of invasive pulmonary aspergillosis

J Schwenck
1   Eberhard Karls Universität Tübingen, Department of Nuclear Medicine and Clinical Molecular Imaging/Werner Siemens Imaging Center, Tübingen
,
N Beziere
2   Eberhard Karls Universität Tübingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tübingen
,
A Maurer
2   Eberhard Karls Universität Tübingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tübingen
,
AM Wild
2   Eberhard Karls Universität Tübingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tübingen
,
H Henneberg
3   University of Duisburg-Essen, Institute for Experimental Immunology and Imaging, Essen
,
G Davies
4   University of Exeter, School of Biosciences, College of Life & Environmental Sciences, Exeter
,
G Reischl
2   Eberhard Karls Universität Tübingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tübingen
,
PR Spycher
5   Paul Scherrer Institute, Center for Radiopharmaceutical Sciences, Villigen
,
JE Wehrmüller
5   Paul Scherrer Institute, Center for Radiopharmaceutical Sciences, Villigen
,
F Boschetti
6   CheMatech, Dijon
,
S Wiehr
2   Eberhard Karls Universität Tübingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tübingen
,
R Schibli
5   Paul Scherrer Institute, Center for Radiopharmaceutical Sciences, Villigen
,
M Gunzer
3   University of Duisburg-Essen, Institute for Experimental Immunology and Imaging, Essen
,
C Thornton
4   University of Exeter, School of Biosciences, College of Life & Environmental Sciences, Exeter
,
BJ Pichler
2   Eberhard Karls Universität Tübingen, Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Tübingen
› Author Affiliations
Further Information

Publication History

Publication Date:
27 March 2019 (online)

 
 

    Ziel/Aim:

    The ubiquitous fungus Aspergillus fumigatus (AF) can cause life-threatening invasive pulmonary aspergillosis (IPA) in immunocompromised patients. Current non-invasive diagnostics lack specificity and sensitivity, while invasive biopsy or bronchoalveolar lavage and subsequent culture of the fungus is slow and carries risks for the patient. Through radiolabeling of an AF specific humanized antibody (JF5), we propose a specific non-invasive method to diagnose IPA in vivo.

    Methodik/Methods:

    JF5 was generated from the variable regions of murine JF5 [1] and human IgG1 framework, conjugated to NODAGA and radiolabeled using [64Cu]CuCl2. Neutropenic C57BL/6 mice were infected intra-tracheally using 4 × 106 AF spores and subsequently injected with 13 MBq of the radiotracer. Simultaneous in vivo PET/MR was performed 3, 24 and 48h after infection using a small animal PET/MRI. In vivo results were validated using ex vivo biodistribution by gamma counting, autoradiography and fluorescence microscopy. For human application the chelator conjugation and radiolabeling were upscaled within a GMP setting and toxicity testing was performed in rodents.

    Ergebnisse/Results:

    Radiolabeled hJF5 revealed high uptake in vivo to AF infection sites and negligible accumulation in control animals. Specific uptake was not observed with [64Cu]CuCl2 nor radiolabeled isotype antibody. [64Cu]NODAGA-hJF5 was found to provide the best uptake ratio 48h after injection in the diseased lungs (17.1 ± 2.5%ID/cc) compared to PBS treated lungs (9.4 ± 1.1%ID/cc) [2]. Toxicity testing showed no adverse effects of repeated dosing. Conjugation procedure and radiolabeling were successfully validated and we expect to obtain first human data within the next weeks.

    Schlussfolgerungen/Conclusions:

    [64Cu]NODAGA-hJF5 proved to be a highly specific and sensitive tracer for IPA, showing very promising results in preclinical models. After recently establishing the GMP compliant synthesis of this tracer and successful systemic toxicity evaluations, first-in-human trials are currently starting.

    Literatur/References:

    [1] Rolle et al. PNAS 2016; 113(8); 1026 – 1033.

    [2] Davies et al., Theranostics. 2017; 7(14): 3398 – 3414.


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