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.