CXCR4-Directed Imaging in Solid Tumors

Frontiers in Oncology

Andreas K. Buck¹  Malte Kircher¹  Constantin Lapa¹  Rudolf A. Werner²  Andreas Schirbel³  Martin G. Pomper⁴  Steven P. Rowe⁴  Takahiro Higuchi⁶  Stefan Kircher⁷  Hans-Jürgen Wester⁸ 

[1] Comprehensive Heart Failure Center, University of Wuerzburg, Wuerzburg, Germany;Department of Nuclear Medicine, Hanover Medical School, Hanover, Germany;Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany;Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States;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;Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;Institute for Pathology, University of Wuerzburg, Wuerzburg, Germany;Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany;

关键词: CXCR4;    [68Ga]Pentixafor;    theranostics;    solid tumors;    chemokine receptor;   

DOI  :  10.3389/fonc.2019.00770

来源: DOAJ

【 摘 要 】

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 (SUVmax) 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 SUVmax 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 (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [68Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax 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.

【 授权许可】

Unknown