A Prospective Evaluation of Chemokine Receptor-4 (CXCR4) Overexpression in High-grade Glioma Using 68Ga-Pentixafor (Pars-Cixafor™) PET/CT Imaging

Habibollah Dadgar; Nasim Norouzbeigi; Majid Assadi; Esmail Jafari; Batool Al-Balooshi; Akram Al-Ibraheem; Abdulredha A Esmail; Fahad Marafi; Mohamad Haidar; Haider Muhsin Al-Alawi; Yehia Omar; Sharjeel Usmani; Andrea Cimini; Maria Ricci; Hossein Arabi; Habib Zaidi

doi:10.1016/j.acra.2024.11.064

A Prospective Evaluation of Chemokine Receptor-4 (CXCR4) Overexpression in High-grade Glioma Using ⁶⁸Ga-Pentixafor (Pars-Cixafor™) PET/CT Imaging

Acad Radiol. 2024 Dec 16:S1076-6332(24)00939-5. doi: 10.1016/j.acra.2024.11.064. Online ahead of print.

Authors

Habibollah Dadgar¹, Nasim Norouzbeigi¹, Majid Assadi², Esmail Jafari², Batool Al-Balooshi³, Akram Al-Ibraheem⁴, Abdulredha A Esmail⁵, Fahad Marafi⁶, Mohamad Haidar⁷, Haider Muhsin Al-Alawi⁸, Yehia Omar⁹, Sharjeel Usmani¹⁰, Andrea Cimini¹¹, Maria Ricci¹², Hossein Arabi¹³, Habib Zaidi¹⁴

Affiliations

¹ Cancer Research Center, RAZAVI Hospital, Imam Reza International University, Mashhad, Iran (H.D., N.N.).
² The Persian Gulf Nuclear Medicine Research Center, Department of Molecular Imaging and Radionuclide Therapy (MIRT), Bushehr Medical University Hospital, Bushehr University of Medical Sciences, Bushehr, Iran (M.A., E.J.).
³ Dubai Nuclear medicine & Molecular imaging Center, Dubai Academic Health corporation, DAHC, United Arab Emirates (B.A.B.).
⁴ Department of Nuclear Medicine, King Hussein Cancer Center, Amman, Jordan (A.A.I.); Division of Nuclear Medicine/Department of Radiology and Nuclear Medicine, University of Jordan, Amman, Jordan (A.A.I.).
⁵ Nuclear Medicine Department, Kuwait Cancer Control Center, Kuwait City, Kuwait (A.A.E.).
⁶ Jaber Alahmad Center of Nuclear Medicine and Molecular Imaging, Kuwait City, Kuwait (F.M.).
⁷ Diagnostic Clinical Radiology Department, American University of Beirut, Beirut, Lebanon (M.H.).
⁸ Nuclear Medicine department, Amir Al-momineen Specialty Hospital, Al-Najaf Governorate, Iraq (H.M.A.A.); Middle Euphrates Cancer Hospital, Al-Najaf Governorate, Iraq (H.M.A.A.).
⁹ PET-CT department at Misr Radiology Center, Heliopolis, Egypt (Y.O.).
¹⁰ Department of Nuclear Medicine Sultan Qaboos Comprehensive Cancer Care and Research Center (SQCCCRC), Seeb, Oman (S.U.).
¹¹ Nuclear Medicine Unit, St. Salvatore Hospital, 67100 L'Aquila, Italy (A.C.).
¹² Nuclear Medicine Unit, Cardarelli Hospital, 86100 Campobasso, Italy (M.R.).
¹³ Division of Nuclear Medicine and Molecular Imaging, Department of Medical Imaging, Geneva University Hospital, CH-1211 Geneva 4, Switzerland (H.A., H.Z.).
¹⁴ Division of Nuclear Medicine and Molecular Imaging, Department of Medical Imaging, Geneva University Hospital, CH-1211 Geneva 4, Switzerland (H.A., H.Z.); Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, Netherlands (H.Z.); Department of Nuclear Medicine, University of Southern Denmark, Odense, Denmark (H.Z.); University Research and Innovation Center, Óbuda University, Budapest, Hungary (H.Z.). Electronic address: [email protected].

PMID: 39690071
DOI: 10.1016/j.acra.2024.11.064

Abstract

Background: While magnetic resonance imaging (MRI) remains the gold standard for morphological imaging, its ability to differentiate between tumor tissue and treatment-induced changes on the cellular level is insufficient. Notably, glioma cells, particularly glioblastoma multiforme (GBM), demonstrate overexpression of chemokine receptor-4 (CXCR4). This study aims to evaluate the feasibility of non-invasive ⁶⁸Ga-Cixafor™ PET/CT as a tool to improve diagnostic accuracy in patients with high-grade glioma.

Methods: In this retrospective analysis, a database of histopathology-confirmed glioma patients with MRI findings consistent with high-grade gliomas was utilized. Within 2 weeks of their MRI, these patients underwent ⁶⁸Ga-Cixafor™ PET/CT scans to assess CXCR4 expression. Both visual scoring based on established criteria and semi-quantitative measures including maximum standardized uptake value (SUV_max) and tumor-to-background ratios (TBR) were calculated to analyze the PET/CT data.

Results: Our retrospective study enrolled 29 histologically confirmed glioma patients with MRI findings consistent with high-grade gliomas. All patients underwent ⁶⁸Ga-Cixafor™ PET/CT scans within 2 weeks of their MRI, specifically at one-hour post-injection time point. Visual assessment based on a standardized scoring system identified 27 positive scans out of 29 (93.1%). Median SUV_max was 2.31 (range: 0.49-9.96) and median TBR was 20 (range: 6.12-124.5). Pathological analysis revealed 5 grade III (17.24%) and 24 grade IV (82.75%) lesions among the 29 patients. Notably, the median SUV_max of grade IV lesions (2.85) was significantly higher than grade III lesions (1.27) (P=0.02). Conversely, there was no significant difference in median TBR between grade IV (20) and grade III (22.37). These findings support the correlation between high CXCR4 expression, particularly in high-grade gliomas, and elevated uptake of ⁶⁸Ga-Pentixafor. While areas with high uptake showed CXCR4 expression, areas with low uptake did not exhibit noticeable expression (data not shown).

Conclusion: This study demonstrated that ⁶⁸Ga-Cixafor™ PET exhibits a TBR with minimal cortical uptake, significantly enhancing glioma detection compared to conventional imaging methods. This, combined with the potential therapeutic capabilities of CXCR4-targeting radiopharmaceuticals, highlights the promise of ⁶⁸Ga-Cixafor™ as a valuable tool for not only improved glioma diagnosis but also personalized treatment strategies.

Keywords: (68)Ga-Pentixafor; CXCR4; GBM; MRI; PET/CT.