CXCR4-Directed Imaging in Solid Tumors

Rudolf A Werner; Stefan Kircher; Takahiro Higuchi; Malte Kircher; Andreas Schirbel; Hans-Jürgen Wester; Andreas K Buck; Martin G Pomper; Steven P Rowe; Constantin Lapa

doi:10.3389/fonc.2019.00770

CXCR4-Directed Imaging in Solid Tumors

Front Oncol. 2019 Aug 14:9:770. doi: 10.3389/fonc.2019.00770. eCollection 2019.

Authors

Rudolf A Werner^{1

2

3}, Stefan Kircher⁴, Takahiro Higuchi^{1

2

5}, Malte Kircher^{1

2}, Andreas Schirbel¹, Hans-Jürgen Wester⁶, Andreas K Buck^{1

2}, Martin G Pomper^{7

8}, Steven P Rowe^{7

8}, Constantin Lapa^{1

2}

Affiliations

¹ Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany.
² Comprehensive Heart Failure Center, University of Wuerzburg, Wuerzburg, Germany.
³ Department of Nuclear Medicine, Hanover Medical School, Hanover, Germany.
⁴ Institute for Pathology, University of Wuerzburg, Wuerzburg, Germany.
⁵ Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
⁶ Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
⁷ Division of Nuclear Medicine and Molecular Imaging, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁸ Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms. Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [⁶⁸Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV_max) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [⁶⁸Ga]Pentixafor findings were further compared to immunohistochemistry and [¹⁸F]FDG PET/CT. Results: On [⁶⁸Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUV_max of 5.4 (range, 1.7-16.0) and a median TBR of 2.6 (range, 0.8-7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUV_max, 16.0; TBR, 7.4). The relatively low uptake on [⁶⁸Ga]Pentixafor was also noted in metastases, exhibiting a median SUV_max of 4.5 (range, 2.3-8.8; TBR, 1.7; range, 1.0-4.1). A good correlation between uptake on [⁶⁸Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [¹⁸F]FDG PET/CT was available, [⁶⁸Ga]Pentixafor exhibited lower uptake in all lesions. Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [⁶⁸Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.

Keywords: CXCR4; [68Ga]Pentixafor; chemokine receptor; solid tumors; theranostics.