68Ga-Pentixafor PET/CT for Detection of Chemokine Receptor CXCR4 Expression in Myeloproliferative Neoplasms

Abstract

C-X-C motif chemokine receptor 4 (CXCR4) is an attractive target for cancer diagnosis and treatment, as it is overexpressed in many solid and hematologic malignancies. This study investigated the feasibility of CXCR4-directed imaging with PET/CT using ⁶⁸Ga-pentixafor to visualize and quantify disease involvement in myeloproliferative neoplasms (MPNs). Methods: Twelve patients with MPNs (4 with primary myelofibrosis, 6 with essential thrombocythemia, and 2 with polycythemia vera) and 5 controls underwent ⁶⁸Ga-pentixafor PET/CT. Imaging findings were compared with immunohistochemical stainings, laboratory data, and splenic volume. Results:⁶⁸Ga-pentixafor PET/CT was visually positive in 12 of 12 patients, and CXCR4 target specificity could be confirmed by immunohistochemical staining. A significantly higher tracer uptake could be detected in the bone marrow of MPN patients (SUV_mean, 6.45 ± 2.34 vs. 4.44 ± 1.24). Dynamic changes in CXCR4 expression determined by ⁶⁸Ga-pentixafor PET/CT corresponded with treatment response. Conclusion:⁶⁸Ga-pentixafor PET/CT represents a novel diagnostic tool to noninvasively detect and quantify the extent of disease involvement in MPNs.

Keywords: CXCR4; PET; molecular imaging; myeloproliferative neoplasms; theranostics.

FIGURE 1.

Display of patient (patient 6) with primary myelofibrosis. ⁶⁸Ga-pentixafor PET/CT (maximum-intensity projections) depicts significantly increased tracer uptake in BM as well as spleen compared with control group.

FIGURE 2.

Response assessment with CXCR4-directed PET/CT imaging (maximum-intensity projections). Shown is example of therapy-induced CXCR4 downregulation in patient with essential thrombocythemia (patient 5).