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

TITLE=CXCR4-Directed Imaging in Solid Tumors

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00770

DOI=10.3389/fonc.2019.00770

ISSN=2234-943X

ABSTRACT=<p>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.</p><p><bold>Methods:</bold> 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 [<sup>68</sup>Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV<sub>max</sub>) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [<sup>68</sup>Ga]Pentixafor findings were further compared to immunohistochemistry and [<sup>18</sup>F]FDG PET/CT.</p><p><bold>Results:</bold> On [<sup>68</sup>Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUV<sub>max</sub> 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<sub>max</sub>, 16.0; TBR, 7.4). The relatively low uptake on [<sup>68</sup>Ga]Pentixafor was also noted in metastases, exhibiting a median SUV<sub>max</sub> of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [<sup>68</sup>Ga]Pentixafor and histological derived CXCR4 expression was noted (<italic>R</italic> = 0.62, <italic>P</italic> &lt; 0.05). In the 3 patients in whom [<sup>18</sup>F]FDG PET/CT was available, [<sup>68</sup>Ga]Pentixafor exhibited lower uptake in all lesions.</p><p><bold>Conclusions:</bold> In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [<sup>68</sup>Ga]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.</p>