Value of Chemokine Receptor CXCR4 Imaging for Diagnosis and Prognostic Evaluation in Lymphoproliferative Diseases

Overview

Chemokine receptor CXCR4 is normally expressed on T-lymphocytes, B-lymphocytes, monocytes, macrophages, neutrophils and eosinophils as well as hematopoietic stem and progenitor cells (HSPC) in the bone marrow. 68Ga-Pentixafor PET/CT represents a promising method for the in vivo assessment of the CXCR4 expression status in cancer patients, especially in hematologic malignancies. This prospective study is going to investigate whether metabolic characterization by 68Ga-Pentixafor PET/CT may be superior for diagnosis, risk stratification, and the prognostic evaluation in lymphoproliferative diseases.

Lymphoma: The marginal zone lymphoma, plasma cell lymphoma, T-cell-lymphoma frequently do not present with an elevated FDG uptake. However, lymphoma is a frequent cancer with high CXCR4 expression. The previous studies showed 68Ga-pentixafor-PET seems to be a highly selective and specific method for the in vivo quantification of CXCR4 expression. Thus, our study is going to investigate the value of 68Ga-pentixafor-PET/CT for the diagnosis and prognostic evaluation of CXCR4 expression in lymphoma. Multiple myeloma: Multiple myeloma (MM) is characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. Minimal residual disease (MRD) status is an important predictor of clinical outcome in MM. But it is difficult to assess the accurate MRD status because of the significant heterogeneity characterizing with 18F-FDG PET/CT. Studies showed Chemokine receptor CXCR4 was expressed in MM cells and CXCR4-targeting molecular imaging-68Ga-Pentixafor PET/CT could be a promising technique to evaluate the extent of MM with higher accuracy. This prospective study is going to investigate the value of 68Ga-Pentixafor PET/CT for the diagnosis and prognostic evaluation of CXCR4 expression in MM. Leukemia： Leukemia is the second largest family of hematological malignancies after the lymphomas, and, depending on the subtype, may show a considerable overlap of histological features with the latter. The four main kinds of leukemia are, in the order of their prevalence. Imaging has traditionally played a limited role in the work-up of leukemias, with regard to detection, staging, and response assessment. 18F-FDG PET/CT is not recommended for routine evaluation of CLL, because the disease shows low uptake in the majority of cases. Although, the clinical utility of MRI lies in the detection of bone marrow abnormalities that are suspicious for leukemia in adult and pediatric patients with unclear musculoskeletal symptoms with its reduced radiation dose (in comparison with PET/CT). However, it may become more attractive with the use of newer, non-FDG PET radiotracers. High CXCR4 expression is known to be associated with poor prognosis in CLL. Recently, the feasibility of 68Ga-Pentixafor PET has also been demonstrated for CLL and AML. This prospective study is going to investigate the value of 68Ga-Pentixafor PET/CT for the diagnosis and prognostic evaluation of CXCR4 expression in leukemia.