Immunohistochemical detection of chemokine receptor 4 expression in chronic osteomyelitis confirms specific uptake in 68Ga-Pentixafor-PET/CT

Yvonne Bouter; Birgit Meller; Carsten O. Sahlmann; Bettina J. Wolf; Laura Langer; Jens P. Bankstahl; Hans J. Wester; Saskia Kropf; Johannes Meller; Caroline Bouter

doi:10.3413/Nukmed-0971-18-04

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2018; 57(05): 198-203
DOI: 10.3413/Nukmed-0971-18-04

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Immunohistochemical detection of chemokine receptor 4 expression in chronic osteomyelitis confirms specific uptake in ⁶⁸Ga-Pentixafor-PET/CT

Der immunhistochemische Nachweis CXCR4-exprimierender Lymphozyten bei chronischer Osteomyelitis bestätigt einen spezifischen Uptake in der ⁶⁸Ga-Pentixafor-PET/CT

Yvonne Bouter

²Division of Molecular Psychiatry, Georg-August-University Göttingen, Göttingen, Germany

,

Birgit Meller

¹Department of Nuclear Medicine, Georg-August-University Göttingen, Göttingen, Germany

,

Carsten O. Sahlmann

¹Department of Nuclear Medicine, Georg-August-University Göttingen, Göttingen, Germany

,

Bettina J. Wolf

⁵Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany

,

Laura Langer

⁵Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany

,

Jens P. Bankstahl

⁵Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany

,

Hans J. Wester

³Pharmaceutical Radiochemistry,Technical University of Munich, Garching, Germany

,

Saskia Kropf

⁴SCINTOMICS GmbH, Lindach 4, 82256 Fuerstenfeldbruck, Germany

,

Johannes Meller

¹Department of Nuclear Medicine, Georg-August-University Göttingen, Göttingen, Germany

,

Caroline Bouter

¹Department of Nuclear Medicine, Georg-August-University Göttingen, Göttingen, Germany

› Author Affiliations

Abstract

Summary

Previous findings of our group showed the chemokine receptor CXCR4 as a suitable target in PET/CT-imaging of axial bone infections, early postoperative osteomyelitis and periprosthetic infections. The aim of this study was to verify specific uptake of ⁶⁸Ga-Pentixafor in chronic osteomyelitis. Methods: 29 consecutive patients who underwent ⁶⁸Ga-Pentixafor-PET/CT with clinically suspected osteomyelitis were evaluated retrospectively. Bone tissues of 6 patients were available and evaluated by immunohistochemical staining for CXCR4 and autoradiography with ⁶⁸Ga-Pentixafor. Staining was performed with an anti-CXCR4 antibody. In order to detect lymphocytic infiltration and CXCR4-expressing lymphocytes double immunofluorescence with an anti-CD3 and anti-CXCR4 antibody was performed. Results: ⁶⁸Ga-Pentixafor-PET/ CT was true positive in 16 and true negative in 13 patients. In available bone tissue samples, immunohistochemical staining of CXCR4 expression and autoradiography with ⁶⁸Ga-Pentixafor was highly positive. Double immunofluorescence was able to detect CXCR4-expressing T-lymphocytes within all bone samples while a control sample of noninfected tibial bone was negative for CXCR4. Conclusion: ⁶⁸Ga-Pentixafor-PET/CT specifically shows CXCR4-expressing immune cells in chronic osteomyelitis and is therefore a suitable method for imaging chronic infection of the skeleton.

Zusammenfassung

Der Chemokinrezeptor CXCR4 konnte in einer Pilotstudie unserer Arbeitsgruppe als geeignete Zielstruktur zur PET/CT-Bildgebung von frühen postoperativen und periprothetischen Osteomyelitiden sowie Osteomyelitiden im Stammskelett identifiziert werden. In dieser Studie haben wir untersucht, ob ⁶⁸Ga-Pentixafor spezifisch CXCR4-exprimierende Entzündungszellen in einer chronischen Osteomyelitis darstellen kann. Methoden: Es erfolgte eine retrospektive Auswertung von 29 Patienten mit klinischem Verdacht einer chronischen Osteomyelitis, die mittels ⁶⁸Ga-Pentixafor-PET/CT untersucht wurden. Hiervon lagen uns in 6 Fällen Knochengewebe zur immunhistochemischen und autoradiographischen Evaluation vor. Die Immunhistochemie wurde mit einem anti-CXCR4 Antikörper durchgeführt. Des Weiteren wurden ein anti-CD3 und der anti-CXCR4-Antikörper zur Detektion CXCR4-exprimierender Lymphozyten am Ort der Entzündung mittels Doppel- Immunfluoreszenz verwendet. Ergebnisse: Die ⁶⁸Ga-Pentixafor-PET/CT war bei 16 Patienten richtig positiv und bei 13 Patienten richtig negativ. Die Färbungen der verfügbaren Knochenpräparate waren sowohl in der Immunhistochemie als auch in der Autoradiographie deutlich positiv. In der Immunfluoreszenz konnten zudem CXCR4-exprimierende Lymphozyten am Ort der Entzündung in allen Proben nachgewiesen werden. Die Kontrolle eines Präparats einer nicht infizierten distalen Tibia zeigte dagegen keine CXCR4-oder CD3-Expression. Fazit: Mit der ⁶⁸Ga-Pentixafor-PET/CT können spezifisch CXCR4-exprimierende Lymphozyten am Ort der Entzündung nachgewiesen werden. Die ⁶⁸Ga-Pentixafor-PET/CT stellt eine geeignete Methode in der Diagnostik chronischer Osteomyeltiden dar.

Keywords

Osteomyelitis - PET/CT - pentixafor

Schlüsselwörter

Osteomyelitis - PET/CT - Pentixafor

Full Text

References

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